phases
list | enrollmentCount
int64 | allocation
string | interventionModel
string | primaryPurpose
class label | masking
class label | healthyVolunteers
bool | sex
class label | oversightHasDmc
bool | briefSummary
string | detailedDescription
string | conditions
string | conditionsKeywords
string | protocolPdfText
string | numArms
int64 | armDescriptions
string | armGroupTypes
list | numInterventions
int64 | interventionTypes
list | interventionDescriptions
string | interventionNames
string | numLocations
int64 | locationDetails
string | target
int64 | nctid
string |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[
2
] | 47
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This study represents the first-in-human study for CP-751,871. The study aimed to define the safety, tolerability, and maximum tolerated dose of CP-751,871 in patients with multiple myeloma through a dose escalation design.
| null |
Multiple Myeloma
|
IGF-1R inhibitor CP-751871 multiple myeloma
| null | 1
|
arm 1: dose escalation design
|
[
0
] | 1
|
[
0
] |
intervention 1: CP-751,871 was given at doses ranging from 0.025 mg/kg up to 20 mg/kg IV every 4 weeks until disease progression or lack of tolerability
|
intervention 1: CP-751,871
| 6
|
Phoenix | Arizona | United States | -112.07404 | 33.44838
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Tampa | Florida | United States | -82.45843 | 27.94752
Boston | Massachusetts | United States | -71.05977 | 42.35843
Rochester | Minnesota | United States | -92.4699 | 44.02163
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT01536145
|
[
3
] | 185
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
A 48-month open label multi-centered extension study to evaluate the long-term safety, tolerability and efficacy of E2007 in patients with Parkinson's Disease with "wearing off" motor fluctuations and "on" period Dyskinesias.
| null |
Parkinson's Disease
| null | 1
|
arm 1: Subjects entered this open-label extension study from the double-blind core study (E2007-E044-204), and dosed placebo or perampanel. Subjects started this open-label extension study on perampanel 1 mg once daily for two weeks, followed by 2 mg once daily for two weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner.
|
[
0
] | 1
|
[
0
] |
intervention 1: 1mg once daily for two weeks, followed by 2mg once daily for 2 weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner.
|
intervention 1: Perampanel
| 0
| null | 0
|
NCT01634360
|
|
[
2
] | 12
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 0NONE
| true
| 2MALE
| false
|
The objectives of this study were to characterize the effects of food on the pharmacokinetics (PK) and tolerability of BIA 9-1067 in healthy male subjects.
|
Methodology: Single center, randomized, single dose, open-label, 2-period, 2-sequence, crossover study.
|
Parkinson
|
Opicapone, Parkinson, Bial, BIA 9-1067
| null | 2
|
arm 1: A single 50 mg dose of BIA 9-1067 (2 x 25 mg capsules) was to be administered on:
Period 1: Fed Washout Period (7days) Period 2: Fasted arm 2: A single 50 mg dose of BIA 9-1067 (2 x 25 mg capsules) was to be administered on:
Period 1: Fasted Washout Period (7days) Period 2: Fed
|
[
0,
0
] | 1
|
[
0
] |
intervention 1: A single oral dose of 50 mg (2 x 25 mg capsules) was administered in the morning of each study period under fasting or fed conditions. The two single dose administrations were separated by a wash-out of 7 days.
|
intervention 1: BIA 9-1067
| 1
|
Mount Royal | Quebec | Canada | -73.64918 | 45.51675
| 0
|
NCT02071823
|
[
5
] | 75
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this study is to help scientist better understand the effect of a 12-week single daily evening dose of ramelteon (Rozerem ©), a drug that has been approved by the U. S. Food and Drug Administration (FDA) for the treatment of insomnia (trouble falling asleep or staying asleep). The study will measure levels of inflammation, fasting insulin and fasting glucose (sugar) in subjects who are taking either ramelteon (8 mg) or placebo.
| null |
Insomnia
|
Insomnia
| null | 2
|
arm 1: Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. arm 2: 15 subjects will be randomized to receive the placebo
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: None intervention 2: None
|
intervention 1: ramelteon intervention 2: placebo
| 0
| null | 0
|
NCT02156271
|
[
0
] | 26
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This is an open label compassionate use study of subcutaneously administered methylnaltrexone (MNTX) in participants with advance medical illness and opioid-induced constipation.
| null |
Opioid-induced Constipation
| null | 1
|
arm 1: Participants will receive single dose of MNTX 0.15 milligrams per kilogram (mg/kg) subcutaneously (SC). Subsequent dosing could be adjusted upward (to a maximum of 0.3 mg/kg) to achieve a desired clinical response or decreased to improve tolerability.
|
[
0
] | 1
|
[
0
] |
intervention 1: Methylnaltrexone will be administered as per the dose and schedule specified in the arm.
|
intervention 1: Methylnaltrexone
| 1
|
Tarrytown | New York | United States | -73.85875 | 41.07621
| 0
|
NCT01368562
|
|
[
3
] | 250
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This is a dose-ranging study to evaluate the efficacy, safety and tolerability of a range of doses of GSK189075 (an SGLT2 inhibitor) compared to placebo, administered over 12 weeks in treatment-naive subjects with type 2 diabetes mellitus
| null |
Diabetes Mellitus, Type 2
|
Diabetes mellitus HbA1c
| null | 2
|
arm 1: Participants will receive GSK189075 for 12 weeks arm 2: Participants will receive GSK189075 matching Placebo for 12 weeks
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: GSK189075 is available as a white, capsule-shaped tablet dosage form containing 50mg, 125mg, 250mg or 500mg of GSK189075 per tablet intervention 2: Available as Placebo matching tablet to GSK189075
|
intervention 1: GSK189075 intervention 2: Placebo
| 157
|
Mesa | Arizona | United States | -111.82264 | 33.42227
Artesia | California | United States | -118.08312 | 33.86585
Buena Park | California | United States | -117.99812 | 33.86751
Fresno | California | United States | -119.77237 | 36.74773
Greenbrae | California | United States | -122.5247 | 37.94854
La Jolla | California | United States | -117.2742 | 32.84727
Norwalk | California | United States | -118.08173 | 33.90224
Petaluma | California | United States | -122.63665 | 38.23242
Sacramento | California | United States | -121.4944 | 38.58157
San Mateo | California | United States | -122.32553 | 37.56299
Santa Ana | California | United States | -117.86783 | 33.74557
Tarzana | California | United States | -118.55397 | 34.17334
Torrance | California | United States | -118.34063 | 33.83585
Deland/Florida | Florida | United States | N/A | N/A
Hollywood | Florida | United States | -80.14949 | 26.0112
Jacksonville/Florida | Florida | United States | N/A | N/A
Miami | Florida | United States | -80.19366 | 25.77427
Miami | Florida | United States | -80.19366 | 25.77427
Ocoee/Florida | Florida | United States | N/A | N/A
Saint Cloud | Florida | United States | -81.28118 | 28.2489
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Bloomingdale | Illinois | United States | -88.0809 | 41.95753
Chicago | Illinois | United States | -87.65005 | 41.85003
Oak Brook | Illinois | United States | -87.92895 | 41.83281
South Bend | Indiana | United States | -86.25001 | 41.68338
Lafayette | Louisiana | United States | -92.01984 | 30.22409
Lake Charles | Louisiana | United States | -93.2044 | 30.21309
Oxon Hill | Maryland | United States | -76.9897 | 38.80345
Boston | Massachusetts | United States | -71.05977 | 42.35843
Gulfport | Mississippi | United States | -89.09282 | 30.36742
Jackson | Mississippi | United States | -90.18481 | 32.29876
Kosciusko | Mississippi | United States | -89.58956 | 33.058
Rolling Fork | Mississippi | United States | -90.87816 | 32.90652
Chesterfield | Missouri | United States | -90.57707 | 38.66311
Saint Louis/Missouri | Missouri | United States | N/A | N/A
Henderson | Nevada | United States | -114.98194 | 36.0397
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Clifton | New Jersey | United States | -74.16376 | 40.85843
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Commack | New York | United States | -73.29289 | 40.84288
Ithaca | New York | United States | -76.49661 | 42.44063
New York | New York | United States | -74.00597 | 40.71427
Asheboro/North Carolina | North Carolina | United States | N/A | N/A
Canal Fulton | Ohio | United States | -81.59762 | 40.88978
Bensalem/Pennsylvania | Pennsylvania | United States | N/A | N/A
West Chester | Pennsylvania | United States | -75.60804 | 39.96097
Manning | South Carolina | United States | -80.21091 | 33.69516
Simpsonville | South Carolina | United States | -82.25428 | 34.73706
Athens/Tennessee | Tennessee | United States | N/A | N/A
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Harlingen/Texas | Texas | United States | N/A | N/A
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
Midland | Texas | United States | -102.07791 | 31.99735
San Anonio | Texas | United States | N/A | N/A
San Antonio | Texas | United States | -98.49363 | 29.42412
Burke | Virginia | United States | -77.27165 | 38.79345
Bellevue | Washington | United States | -122.20068 | 47.61038
Langley | British Columbia | Canada | -122.65883 | 49.10107
Bathurst | New Brunswick | Canada | -65.65112 | 47.61814
Bay Roberts | Newfoundland and Labrador | Canada | -53.26478 | 47.59989
Brampton | Ontario | Canada | -79.76633 | 43.68341
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Oakville | Ontario | Canada | -79.68292 | 43.45011
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Thornhill | Ontario | Canada | -79.4163 | 43.80011
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
L'Ancienne-Lorette | Quebec | Canada | -71.35191 | 46.79392
Québec | N/A | Canada | -71.21454 | 46.81228
Brno | N/A | Czechia | 16.60796 | 49.19522
Brno | N/A | Czechia | 16.60796 | 49.19522
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Pärnu | N/A | Estonia | 24.49711 | 58.38588
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Allmendingen | Baden-Wurttemberg | Germany | 9.72419 | 48.33052
Wangen | Baden-Wurttemberg | Germany | 9.83247 | 47.6895
Großheirath | Bavaria | Germany | 10.9505 | 50.17603
Hohenau | Bavaria | Germany | 13.48825 | 48.84983
Künzing | Bavaria | Germany | 13.08333 | 48.66667
Munich | Bavaria | Germany | 11.57549 | 48.13743
Munich | Bavaria | Germany | 11.57549 | 48.13743
Parsberg | Bavaria | Germany | 11.71834 | 49.16074
Ruhmannsfelden | Bavaria | Germany | 12.98347 | 48.98327
Sulzbach-Rosenberg | Bavaria | Germany | 11.74598 | 49.50126
Falkensee | Brandenburg | Germany | 13.0927 | 52.56014
Brinkum/Stuhr | Lower Saxony | Germany | N/A | N/A
Einbeck | Lower Saxony | Germany | 9.86961 | 51.82018
Hanover | Lower Saxony | Germany | 9.73322 | 52.37052
Lüneburg | Lower Saxony | Germany | 10.41409 | 53.2509
Tostedt | Lower Saxony | Germany | 9.71667 | 53.28333
Haßloch | Rhineland-Palatinate | Germany | 8.25806 | 49.36278
Ingelheim | Rhineland-Palatinate | Germany | 8.05883 | 49.97078
Dresden | Saxony | Germany | 13.73832 | 51.05089
Freital | Saxony | Germany | 13.6488 | 51.00166
Schmiedeberg | Saxony | Germany | 13.67622 | 50.83644
Wolmirstedt | Saxony-Anhalt | Germany | 11.62945 | 52.24856
Lübeck | Schleswig-Holstein | Germany | 10.68729 | 53.86893
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Bangalore | N/A | India | 77.59369 | 12.97194
Bangalore | N/A | India | 77.59369 | 12.97194
Chennai | N/A | India | 80.27847 | 13.08784
Mumbai | N/A | India | 72.88261 | 19.07283
Pune | N/A | India | 73.85535 | 18.51957
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Cuernavaca | Morelos | Mexico | -99.23075 | 18.9261
Mérida | Yucatán | Mexico | -89.62318 | 20.967
Durango | N/A | Mexico | -104.65756 | 24.02032
Rotorua | N/A | New Zealand | 176.24516 | -38.13874
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Porąbka | N/A | Poland | 19.21835 | 49.81716
Siemianowice Śląskie | N/A | Poland | 19.02901 | 50.32738
Wroclaw | N/A | Poland | 17.03333 | 51.1
Aibonito/Puerto Rico | Puerto Rico | Puerto Rico | N/A | N/A
Trujillo Alto/Puerto Rico | Puerto Rico | Puerto Rico | N/A | N/A
Caguas | N/A | Puerto Rico | -66.0485 | 18.23412
Carolina | N/A | Puerto Rico | -65.95739 | 18.38078
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
Rio Piedras | N/A | Puerto Rico | -66.04989 | 18.39745
Arad | N/A | Romania | 21.31667 | 46.18333
Brasov | N/A | Romania | 25.60613 | 45.64861
Sfântu Gheorghe | N/A | Romania | 25.78333 | 45.86667
Timișoara | N/A | Romania | 21.22571 | 45.75372
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint-Peterburgh | N/A | Russia | N/A | N/A
Tomsk | N/A | Russia | 84.98204 | 56.50032
Tyumen | N/A | Russia | 65.52722 | 57.15222
Lenasia South | Gauteng | South Africa | N/A | N/A
Bellville | N/A | South Africa | 18.62847 | -33.90022
Gauteng | N/A | South Africa | N/A | N/A
Parow | N/A | South Africa | 18.59992 | -33.89723
Roodepoort | N/A | South Africa | 27.8725 | -26.1625
Dnipropetrovsk | N/A | Ukraine | 35.04066 | 48.46664
Kyiv | N/A | Ukraine | 30.5238 | 50.45466
Vinnitsa | N/A | Ukraine | 37.71861 | 49.84639
| 0
|
NCT00495469
|
[
4
] | 18
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The painful episode is the most common problem experienced by children with sickle cell disease. Although various treatments are available during painful episodes, the medication most commonly given for pain is a pain medication such as morphine. Fluids are also used. Even with these treatments, many children still have severe pain that is difficult to control. In addition to pain medications, there are other medications that may be useful. Methylprednisolone (solumedrol) and prednisone are a group of medications called steroids that may be helpful for painful episodes. These medications are known to lower the amount of inflammation (this means swelling, tenderness, and soreness) in the body. Because this medication may help with your pain, you are being asked to be a part of this study. These types of medications are used in other illnesses such as asthma, especially during times when the illness has gotten worse.
The main purpose of this study is to see if the methylprednisolone and prednisone will lower the amount of pain and the length of hospital stay.
In addition to the pain medication you will normally receive, you will be assigned to one of 2 groups: 1) the experimental group with the active form of the medicine, or 2) a comparison group without the active form of the medicine. In either group, you will still receive all of the treatments you would normally receive for a painful episode, including pain medicines and fluids. You and your doctors will not know what group you will be assigned.
If you decide to be a part of the study the following will happen:
For the first 5 days, you will be asked to: 1) describe your current pain (0=no pain to 10=a lot of pain), worst pain (0=no pain to 10=a lot of pain), least pain (0=no pain to 10=a lot of pain), and the amount of pain relief (0=no relief to 10=complete relief); 2) describe any signs or symptoms you feel, including filling out a pain scale form each day; 3) and take the medicines for 5 days, either at home or when in the hospital. Thirty days after the study, a study researcher will call and will ask questions about your pain, any painful episodes, and any medications you had. If you are discharged home sooner than 5 days after the start of the study, research staff will call you to ask you these questions, remind you to fill out your pain forms, and remind you to take your medicine. If you are discharged home, you will be given pain scales to fill out each day at home.
|
In the United States, 9% of African Americans have sickle cell trait and 1 in 600 has sickle cell disease. Vaso- occlusive crises in sickle cell disease remain a frequent cause of severe pain, leading to emergency room visits, hospitalizations, and dependence upon narcotics for analgesia. Current treatments for vaso-occlusive crises includes IV analgesia with narcotics, NSAIDS, and hydration. Admissions can be frequent, prolonged, and can significantly diminish quality of life.
Understanding the pathophysiology of vaso-occlusive crises helps to find possible treatments. The etiology of vaso- occlusive crises includes HbS polymerization; sickle erythrocyte polymerization; endothelial damage; and inflammation, reperfusion injury, and oxidant radical production (Steinberg et al, Hematology, 2004). For example, hydroxyurea works by increasing the amount of fetal hemoglobin (HbF) and thus inhibiting polymerization, and reduces the incidence of pain by nearly 50%. Glucocorticoids would be expected to exert effects on the endothelium and inflammation.
Vaso-occlusive crises share similar features with other inflammatory processes, including clinical symptoms of swelling, erythema, and warmth; and laboratory findings of leukocytosis and elevated ESR. It has previously been theorized that glucocorticoids, which are used in many other inflammatory disorders, could decrease the duration or severity of vaso-occlusive crises. Methylprednisolone is a corticosteroid which decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability (Takemoto, et al 2004). A randomized, placebo-controlled study of 2 doses of intravenous methylprednisolone for vaso-occlusive crisis showed that the duration of severe pain and the need for inpatient analgesia was decreased in patients who received methylprednisolone; however the intervention patients had more rebound attacks than those who received placebo. (Griffin et al, NEJM, 1994)
Previous studies have examined long-term administration of steroid hormones including testosterone, progesterone, and medroxyprogesterone to patients with sickle cell disease. In placebo-controlled crossover trials, patients who received steroids had fewer vaso-occlusive episodes than placebo-treated patients (Isaacs et al, Lancet,1972; DeCeulaer et al, Lancet, 1982). Initial reports of glucocorticoids for vaso-occlusive crisis include an uncontrolled report of hydrocortisone as adjunctive therapy for VOC (Araujo et al, Blood, 1990). A case report showed efficacy of dexamethasone for vaso-occlusive crisis in children (Robinson et al, Lancet, 1979). The mechanism of steroids effect is uncertain.
In acute chest syndrome, which shares many clinical features with vaso-occlusive crises, intravenous therapy with dexamethasone has been shown to reduce the length of hospital stay, prevent clinical deterioration, and reduce the need for blood transfusion (Bernini et al, Blood, 1998).
In a placebo-controlled trial of high-does methylprednisolone for VOC, patients with severe pain requiring hospital admission were randomized to receive methylprednisolone or placebo (15 mg/kg to maximum 1 gram) at admission and again 24 hours later. The duration of inpatient analgesia was significantly shorter in patients who received methylprednisolone. However, patients who received methylprednisolone were much more likely to be readmitted shortly after finishing therapy. In addition, the study was criticized because patients did not rate their pain, and very few patients received patient-controlled analgesia while hospitalized.
Since this trial was published, there have been other advances in the standard management of VOC. Ketorolac, a non-steroidal analgesic, is now a standard adjunctive therapy, and most patients are quickly placed on patient-controlled analgesia. In addition, more patients now receive chronic, preventative therapies such as hydroxyurea and chronic transfusions.
We are therefore interested in repeating and expanding upon the results obtained several years ago and in evaluating the role of steroids if given over a slightly longer period of time.
The primary objective of this study is to determine whether the use of high-dose methylprednisolone followed by steroid taper decreases the duration of hospitalization and severity of pain in VOC of sickle cell disease.
Primary Hypothesis: The experimental group treated with high-dose methylprednisolone and steroid taper plus conventional therapy will have an improvement in pain scores using a 10-point scale.
In addition, the secondary objectives were:
1. duration of inpatient admissions
2. to examine the number and type of complications and side effects (infection, hypertension, and GI bleeding)
3. to determine rate of recurrent episodes of pain within one month of treatment.
4. to determine whether the amount of analgesic used will decrease during the hospitalization, as measured by the # of days in which IV opioids were given.
|
Sickle Cell Disease Vaso-occlusive Crisis
|
Sickle cell disease vaso-occlusive crisis steroid treatment
| null | 2
|
arm 1: Receipt of methyprednisolone pulse dose: 15mg/kg to a maximum of 1 gram; following this, the patients also received a steroid taper with oral prednisone:Day 2: Prednisone 2mg/kg PO BID Day 3: Prednisone 2mg/kg PO daily Day 4: Prednisone 1mg/kg PO daily Day 5: Prednisone 1mg/kg PO daily arm 2: Patients receiving usual care, with receipt of placebo (saline in lieu of intravenous methylprednisolone infusion or a number of placebo pills equivalent in number to what would have been received for the prednisone.
|
[
0,
2
] | 2
|
[
0,
10
] |
intervention 1: Day 1: Solumedrol 15 mg/kg (maximum 1 gram) Day 2: Prednisone 2mg/kg PO BID Day 3: Prednisone 2mg/kg PO daily Day 4: Prednisone 1mg/kg PO daily Day 5: Prednisone 1mg/kg PO daily intervention 2: Patients received normal saline in lieu of intravenously-administered methylprednisolone and placebo pills equal in number to the steroid pills received in the steroid arm
|
intervention 1: Steroid arm intervention 2: Placebo
| 1
|
Houston | Texas | United States | -95.36327 | 29.76328
| 0
|
NCT00263562
|
[
4
] | 2,414
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This is a 20-week clinical trial in participants with primary hypercholesterolemia or mixed dyslipidemia to demonstrate the effect of MK-0524B compared to MK-0524A + Simvastatin on lipid values.
| null |
Primary Hypercholesterolemia Mixed Dyslipidemia
| null | 4
|
arm 1: After a 2-week placebo run-in, participants will receive MK-0524B (0.9 g/simvastatin 10 mg) for 4 weeks, then MK-0524B 1.8g /20 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 20 mg for 8 weeks. arm 2: After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 10 mg for 4 weeks, then co-administered MK-0524A 2g +simvastatin 20 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/20 mg combination tablet for 8 weeks. arm 3: After a 2-week placebo run-in, participants will receive MK-0524B 0.9g/40 mg combination tablet for 4 weeks, then MK-0524B 1.8g /40 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 40 mg for 8 weeks. arm 4: After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 40 mg for 4 weeks, then co-administration MK-0524A 2g +simvastatin 40 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/40 mg combination tablet for 8 weeks.
|
[
0,
0,
0,
0
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: None intervention 2: Extended-release(ER) niacin/Laropiprant (MK-0524) Combination tablet intervention 3: None intervention 4: None
|
intervention 1: Comparator: simvastatin intervention 2: MK-0524A intervention 3: Placebo intervention 4: MK-0524B
| 0
| null | 0
|
NCT00479882
|
|
[
4
] | 7,808
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 1FEMALE
| true
|
This study will evaluate the effectiveness and safety of denosumab in treating women with Postmenopausal Osteoporosis.
| null |
Osteoporosis
|
Postmenopausal Osteoporosis
| null | 2
|
arm 1: Placebo administered subcutaneously once every 6 months for 3 years. arm 2: Denosumab 60 mg administered subcutaneously once every 6 months (Q6M) for 3 years.
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: Placebo administered by subcutaneous injection intervention 2: Denosumab 60 mg administered by subcutaneous injection
|
intervention 1: placebo intervention 2: Denosumab
| 0
| null | 0
|
NCT00089791
|
[
3
] | 366
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
Teva is developing 40 mg/ml Glatiramer Acetate (GA) Injection , administered once daily under the skin, for the treatment of ALS. The study drug is a higher dose formulation of Copaxone® (20 mg/ml GA), a marketed medication, approved for the treatment of relapsing-remitting multiple sclerosis. GA is an immunomodulating drug that has anti inflammatory and neuroprotective properties, which are believed to be of therapeutic value in ALS. The study treatment duration is 1 year (52 weeks).
| null |
Amyotrophic Lateral Sclerosis
| null | 2
|
arm 1: Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day. arm 2: Pre-filled syringe of matching placebo, administered subcutaneously once a day.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: parenteral drug intervention 2: None
|
intervention 1: 40 mg glatiramer acetate intervention 2: Placebo
| 7
|
Haarlem | N/A | Belgium | N/A | N/A
Leuven | N/A | Belgium | 4.70093 | 50.87959
Paris | N/A | France | 2.3488 | 48.85341
Mörfelden-Walldorf | N/A | Germany | 8.58361 | 49.99472
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Milan | N/A | Italy | 12.59836 | 42.78235
Aylesbury | N/A | United Kingdom | -0.81458 | 51.81665
| 1
|
NCT00326625
|
|
[
5
] | 80
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| true
|
The primary aim of this randomized clinical trial is to compare the effect of misoprostol vs extra amniotic saline infusion via a catheter (EASI) for cervical ripening on the proportion of patients delivered by cesarean section for fetal intolerance of labor versus vaginal delivery. The primary hypothesis is that patients undergoing cervical ripening with EASI catheter are less likely to undergo cesarean section for fetal intolerance of labor when compared to women who receive misoprostol.
|
Induction of labor is a common obstetrical practice. In fact, the rate of induction has risen to 184/1000 live births. It is well known that a favorable Bishop score, defined as Bishop score 5-8, improves the safety and success rate for induction of labor and vaginal delivery. Several methods for cervical ripening, both mechanical and pharmacological, have been developed to improve Bishop score in women eligible for induction of labor with an unfavorable cervix. These methods include: misoprostol, dinoprostone, intracervical catheter with and without extra-amniotic saline infusion, and laminaria.
Several studies have investigated the optimum cervical ripening agent, and review of current literature supports that misoprostol given in a dose of 25 micrograms every 4 hours intravaginally as the most efficacious and inexpensive regimen while maintaining safe maternal and fetal outcomes. Several studies have shown that misoprostol has a significantly shorter time to delivery compared with other methods of ripening. In fact, in a 2003 Cochrane Database Systematic Review, misoprostol was shown to have increased cervical ripening effectiveness and reduced failure to achieve vaginal delivery in 12-24 hours. Further, while uterine hyper-stimulation and tachysystole were more common in the misoprostol groups, no adverse neonatal outcomes were described. However, misoprostol has been shown to have a higher incidence of cesarean section for fetal intolerance to labor compared to other cervical ripening methods including EASI. Several studies support the ideal route of administration and dosage of misoprostol to be 25 micrograms every 4 hours intravaginally. This regimen leads to effective cervical ripening while reducing the dose-dependent effect of misoprostol on uterine tachysystole and hyperstimulation. Another aspect to consider in cervical ripening method is cost. Misoprostol is much less expensive than other methods including dinoprostone. In fact, one article reports that the average cost per patient for misoprostol treatment was $85 compared to $606 for dinoprostone insert.
Extra-amniotic saline infusion (EASI) has been introduced as a mechanical, non-pharmacological cervical ripening method. It involves placement of a Foley catheter through the cervix and is supplemented with continuous extra-amniotic infusion of saline. This is thought to improve prostaglandin release, resulting in shortened duration of labor. Several studies have been performed to determine the safety and efficacy of the EASI method.
Since misoprostol is efficacious, safe, and inexpensive, it is a superior method for cervical ripening and will act as a control for an experimental group undergoing cervical ripening with the EASI catheter. Our hypothesis is that cervical ripening with the EASI method will result in fewer cesarean sections for fetal intolerance to labor as compared to misoprostol. Furthermore, patients undergoing cervical ripening with EASI will experience a shorter time to delivery, have less expense, have fewer adverse effects, and will be more satisfied with EASI catheter than with misoprostol.
|
Cesarean Section
|
Pregnancy Extra amniotic saline infusion Misoprostol Labor induction
| null | 2
|
arm 1: Patients randomized to this arm will receive 25 micrograms of misoprostol every four hours. arm 2: Patients randomized to this arm will receive extra amniotic saline infusion (EASI) administered via catheter
|
[
1,
0
] | 2
|
[
0,
1
] |
intervention 1: Misoprostol,25 micrograms every 4 hours. intervention 2: A catheter with extra amniotic saline infusion (EASI) is placed in the uterus and applies pressure to the cervix to cause it to ripen
|
intervention 1: Misoprostol intervention 2: Catheter
| 1
|
Maywood | Illinois | United States | -87.84312 | 41.8792
| 0
|
NCT00383942
|
[
3
] | 24
|
RANDOMIZED
|
CROSSOVER
| 7BASIC_SCIENCE
| 4QUADRUPLE
| false
| 0ALL
| true
|
This study will examine the effects of atorvastatin, a statin (drug that lowers cholesterol) on the human immunodeficiency virus (HIV). If not treated, HIV infection causes an incurable, progressive deficiency in the immune system that leads to death, usually from disease that takes advantage of weakened immunity. Previous studies, however, have suggested that if the amount of cholesterol in infected cells is reduced, multiplication of HIV is also reduced. In this study, researchers will examine the HIV viral loads, that is, amount of the virus in the blood. They will evaluate the composition of the strain of the virus that patients carry (HIV genotype), response of the immune system to the virus, and how genes may determine the way in which the drug may or may not work against the strain of virus. Researchers plan to enroll 22 participants, anticipating a study to last 30 weeks for each participant.
Patients ages 18 or older with HIV infection, who are not pregnant or breastfeeding, who do not have a known allergy to atorvastatin use, and who have not had a serious illness or infection that required hospitalization within the 30 days before entering the study may be eligible for this study. They will be assigned to random groups: one that to receive atorvastatin and the other to receive a placebo, which has no effect on cholesterol or ability of the HIV infection to multiply. Patients will remain in their groups and treatments for 8 weeks. At the completion of 8 weeks, no matter the study group, all patients will be required to discontinue all study-related medications for 4 weeks. After that period, the study assignments will be switched, so that those previously taking the placebo will take atorvastatin, and vice versa. The study will proceed for another 8 weeks, followed by a period of stopping study-related medications and patients being observed for 4 weeks. Throughout the study, patients will have regularly scheduled visits at the clinic. At those visits there will be collection of blood samples, assessments of symptoms, physical examinations, and questionnaires to complete. Blood tests may require fasting beforehand, and blood samples will be used in standard tests, including those regarding the liver, kidneys, muscles, blood cells, and pregnancy status. Specialized blood tests will determine viral load, effects of the drug on the immune cells, and genetic influence on the drug's effectiveness.
|
This protocol is a randomized, double blind, placebo controlled trial designed to study the effects of the lipid lowering statin, atorvastatin on HIV-1 viremia.
Untreated HIV-1 infection results in an incurable, progressive immunodeficiency and death, usually from opportunistic infections. Combination antiretroviral therapy (ARV) has been successful in suppressing HIV replication and reducing morbidity and mortality. Long term ARV therapy is associated with the development of HIV-1 drug resistance, and significant adverse side effects including metabolic and cardiovascular complications. Prolonged therapy with certain antiretrovirals is associated with increased risk of cardiovascular disease and a number of dyslipidemic syndromes, including increased levels of cholesterol, LDL, and triglycerides in peripheral blood. New therapeutic strategies to suppress HIV-1 infection are essential.
Previously, in vitro studies suggested that exposure to cholesterol-lowering statins results in decreases in HIV-1 replication. The mechanisms of inhibition remain uncertain, but possibilities include disrupting membrane trafficking or cytoskeletal processes necessary for intracellular transport of viral proteins, or altering cellular activation state necessary for viral gene expression. Initial in vivo studies of the effects of statins on HIV-1 have been largely anecdotal in nature and have yielded conflicting results. Although statin therapy is commonly used in HIV-1 infection, adverse effects from the combination of antiretrovirals and statins are possible. A more thorough understanding of the effects of statins on HIV-1 replication is essential to determine the potential therapeutic effect and to investigate the risks and benefits of this approach in vivo.
We plan to conduct a double blind randomized placebo controlled trial, with a cross over design, to study the effects of atorvastatin in 22 HIV-infected patients not currently taking antiretroviral therapy. Patients will be randomized to receive either placebo or atorvastatin 80mg for 8 weeks. After a 4-week wash out period patients on the atorvastatin arm will crossover to placebo and, vice versa patients in the placebo arm will cross over to atorvastatin for an additional 8 weeks. Upon completion of study medications all patients will be followed for 4 weeks. Each arm will have a minimum of 11 patients each. The primary outcome measure in this study is the effect of lipid lowering agents on HIV-1 RNA levels; additional secondary outcome measures include effects of lipid lowering agents on lipid profile, markers of inflammation and immune activation and investigations of host and viral genetic factors.
|
HIV
|
Viremia Statin HIV Replication Cholesterol Lipid Raft HIV Infection HIV Positive
|
ICF_002.pdf:
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
• Adult Patient or • Parent, for Minor Patient
INSTITUTE:
National Institute of Allergy and Infectious Diseases
STUDY NUMBER:
06-I-0197
PRINCIPAL INVESTIGATOR:
STUDY TITLE:
A Randomized Placebo Controlled Trial of Atorvastatin in HIV Positive Patients Not on
Antiretroviral medications with the Specific Aims of Studying the Effects of Atorvastatin on HIV
Viral Load and Immune Activation Markers
Continuing Review Approved by the IRB on 4/14/08
Amendment Approved by the IRB on 03/20/08 (G)
Date Posted to Web: 05/06/08
Screening
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY
• Adult Patient or • Parent, for Minor Patient
NIH-2514-1 (4-97)
P.A.: 09-25-0099
File in Section 4: Protocol Consent (2)
INTRODUCTION
We invite you to take part in a research study at the National Institutes of Health (NIH).
First, we want you to know that:
Taking part in NIH research is entirely voluntary.
You may choose not to take part, or you may withdraw from the study at any time. In either case, you will not
lose any benefits to which you are otherwise entitled. However, to receive care at the NIH, you must be taking
part in a study or be under evaluation for study participation.
You may receive no benefit from taking part. The research may give us knowledge that may help people in the
future.
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research
treatments they would want to receive (such as blood transfusions). If you have such beliefs, please discuss them with
your NIH doctors or research team before you agree to the study.
Now we will describe this research study. Before you decide to take part, please take as much time as you need to ask
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other
health professional.
Purpose of the Study
HIV, the virus that causes AIDS, grows in the immune cells of the body. Recent research has shown that for the HIV to
multiply (replicate), it has to use some of the normal cell machinery. One of the pathways the virus uses to multiply
requires cholesterol (a kind of fat in the body). Laboratory research has indicated that if the amount of cholesterol in
infected cells is reduced, HIV replication is also decreased. These experiments have been done only in the laboratory and
it is not known whether reducing cholesterol in people infected with HIV will also reduce HIV replication. In this study we
plan to investigate whether the use of cholesterol lowering drugs called statins will reduce HIV replication and lower the
level of HIV in the blood “viral load”. We are studying the effects of one statin called atorvastatin (Lipitor), which has been
approved by the Food and Drug Administration (FDA) for treatment of persons with hyperlipidemia (elevated lipids in the
blood). Atorvastatin is not an approved treatment for HIV infection, and should not be considered a therapy for HIV; even
CONTINUATION SHEET for either:
MEDICAL RECORD
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NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 2 of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
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if it does decrease HIV viral loads (the amount of the HIV virus in your blood), it is unlikely that atorvastatin alone will
control HIV. Atorvastatin is approved by the FDA for the treatment of hypercholesterolemia and is available for use
outside this study. However, atorvastatin is not FDA approved for treatment of HIV infection. As you are likely to have
normal cholesterol you may not receive any benefit from taking atorvastatin. The desire to take atorvastatin should not
be a reason for you to volunteer to take part in this study.
Study Procedures
You will first come to the clinic for a screening visit, after signing this screening consent you will undergo testing to
determine whether or not you qualify for the study. Testing at this visit will include blood and urine tests.You will be
required to come fasting for the tests, as eating prior to testing may result in changes to your cholesterol (fat in the
blood). Tests will include standard tests to study the health of your liver, kidney, muscle and blood and a pregnancy test.
You will undergo specialized tests to determine if you are infected with the hepatitis B or C virus, tests to determine the
amount of HIV virus in your blood “HIV viral load” and also tests to measure your immune cells “CD4 count”. You will be
required to come fasting for this visit because we will check the level of lipids in your blood, which can change if you are
not fasting. You will also undergo a clinical assessment and a physical exam at this visit.
If you are eligible for the study phase of the protocol based on the results of testing done at your screening visit and if
you desire to enroll in the protocol you will enter the study phase. In the study phase, you will sign a new consent that
details the procedures of the study. Briefly, you will be randomly assigned (by chance, like the flip of a coin) to one of
two study groups. One study group will be asked to take atorvastatin, a medicine that reduces cholesterol and may
affect the ability of your virus to multiply. The other study group will take a placebo (something like a sugar pill) that
should have no affect either on the level of your cholesterol or the ability of your virus to multiply. Once you have been
assigned to the study groups, you will remain in your assigned groups/treatments for 8 weeks. Upon completion of 8
weeks, regardless of the study group you were assigned to, you will be required to discontinue all study related
medications for 4 weeks. There may be some circumstances where we may extend this off drug period to a total of 6
weeks. For instance, if you require the influenza vaccination, which can sometimes affect HIV-1 viral RNA levels, we will
administer the standard inactivated vaccine at the beginning of the off drug period, followed by six week wash out. At
the end of this period, you will be asked to switch your study assignments i.e. if you were on the placebo pill you will
switch to the study drug atorvastatin and vice versa if you were on the study drug atorvastatin you will switch to the
placebo pill. You will complete an additional 8 weeks on this assigned study treatment; after this you will stop all study
related treatment and be observed for an additional 4 weeks.
Study Population
We plan to enroll 22 subjects for this study and the anticipated duration on study for each subject is 24weeks. We will
screen as many patients as required to enroll 22 patients onto this study.
Summary of Entry Criteria
To participate in the study you must:
• Be greater than 18 years of age
• Be infected with the HIV-1 virus
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NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 3 of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
• Off all antiretroviral therapy (ART) “medicines taken to control the virus multiplication” for greater than three
months prior to study entry. While off ART you must have a stable viral load ” amount of virus in your blood”
• Be willing to use two methods of contraception during the study period. Adequate methods of birth control
include: condoms, male or female, with or without a spermicide; diaphragm or cervical cap with spermicide;
intrauterine device; any of the methods that require a prescription (such as contraceptive pills or patch,
Norplant, Depo-Provera, and others) or a male partner who has previously undergone a vasectomy,
• If you had been taking ART in the past and are currently not on any medication, there must be no evidence
that when you were taking these medications, these medications were not working against your strain of the
virus what we refer to as “resistance”.
• Be willing to have blood drawn
• Have no known allergy or contraindication to atorvastatin use
• Have the ability to understand and willingness to sign the informed consent
• Be willing to have blood stored for future testing including tests that will study your genes and the genetics of
the virus
• Have a CD4 cell count (a measure of your immune cells) greater than 350 cells/ml
• Have three viral loads that average greater than 1000 copies/ml within a 4 week period.
• Have near normal total cholesterol “ a kind of fat in the body” (i.e lower than 240mg/dl) and an LDL
cholesterol “a kind of fat in the body “ lower than 130mg/dl
• Have near normal results for tests that test the health of your kidney, pancreas, liver, blood and muscles
• Have a negative pregnancy test and not be breast feeding prior to taking the study drug
• Not be on any other medication to lower your cholesterol
• Let your doctor know if you are on any herbal medications or supplements
To Participate in the Study You Must Not
•
Be actively using any recreational drugs or alcohol as this might interfere with your ability to participate in the
study
•
Have had a serious illness or opportunistic infections “illnesses that occur in people with a weakened
immunity” that required hospitalizations in the 30 days prior to entry into the study
•
Have evidence of any cancer or opportunistic illness that will require treatment during the study period except
some forms of skin cancers
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 4 of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
•
Allergy to the study medication “atorvastatin” or any of its components
•
Have had a history of myositis or rhabdomyolysis (diseases that results in muscle injury or swelling
“inflammation”) with use of any statins
•
Have had a history of diseases of the muscle such as poly or dermatomyositis (these are diseases of the
muscle that results in swelling “inflammation” of the muscle)
•
Be on any medications that do not mix “interactions” with the study drug. Please see the attached listing, if
you are on any of these drugs please let your physician know.
•
Use St.Johns wort, as this can increase the amount of study drug in your body.
•
Use grape fruit or grape fruit juice, as this can increase the levels of study drug in your body
•
Be on any medication that might affect your immune response
•
Have a low LDL cholesterol ( a kind of fat in the body) that is lower than 40 mg/dl
•
Have had any vaccines within 6 weeks of entry into the study.
Withdrawal From the Protocol
You may choose to withdraw from the protocol at any time. We may choose to withdraw you from the protocol at any
time if we think it is not in your best interest to continue on the protocol, or if you fail to comply with the requirements of
the protocol or if the Data Safety Monitoring Board (DSMB) “a panel of independent investigators” who will review the
data after we accrue 50 % of the patients” decides to stop the protocol. If the protocol is terminated for unanticipated
reasons subjects will be withdrawn from the study. If you need to start antiretroviral therapy, you will be withdrawn from
the study and referred to your primary physician. Any decision to start antiretroviral therapy will be done in consultation
with your primary physician. If you need to start antiretroviral therapy you should do so after you have discontinued
atorvastatin for at least one week. You may also be withdrawn from the study if blood tests that measure your liver
functions are greater than 3 times the upper limit of normal on two successive measurements.
Duration of Study
The study will take 24 weeks to complete once you have been assigned to one or the other group
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
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CONTINUATION: page 5 of 10 pages
PATIENT IDENTIFICATION
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NIH-2514-2 (10-84)
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Risks/Discomforts/Monitoring
Risks
The possible risks and discomforts from screening for this study are the risks from the blood drawing and the risks from
sample storage. The risks associated include bleeding, bruising, and fainting. To minimize risk, patients will have their
blood taken in the sitting position and will be monitored for 10 minutes after the procedure.
If you are eligible to participate in the study phase of the protocol, there are additional risks from the study medication
and from reductions in your cholesterol, and we will discuss those risks in an additional consent at the time you start
the study phase.
Benefits
You will not benefit from taking part in this study, but the information we learn may help us with the management of HIV
positive patients in the future. This includes the availability of a drug that is frequently used in the management of some
of the complications of drugs currently used to control the virus and may have the potential to control the quantity of
virus and affect the immune response in HIV positive patients.
Compensation
To compensate for your time and inconvenience of this screening visit, you will be paid $70.00
Alternatives to Participation
This study provides no direct benefits to participants. You are in no way obligated to continue in the protocol even if you
are eligible. The alternative to participation is not to enroll.
Additional Information
There will be no cost to you for study medications, clinic visits, examinations or laboratory and test procedures that are
part of this study and that are obtained at the NIH. Medical costs of other treatment outside this study and outside of the
NIH will not be the responsibility of the NIH. The NIH will provide only study-related medical care, and medical care and
medications not directly related to the study must continue to be provided by your personal physician. We will be sending
letters regarding your study participation and your care to your doctor routinely and as needed, and we will also use the
fax and the phone to relay information to your doctor that he or she should know to best care for you. We will not ask
your permission for each of these contacts. We will contact the physician you have named as your doctor, but you may
give us a different physician to contact instead at any time. Once your participation in this study is completed, you will
not be eligible for continuing care at NIH, unless you are eligible for another study at the NIH, but your doctors at NIH will
be glad to provide telephone consultation to your own doctor on request. During the study, you will be told about any
research that relates to your study, especially any findings from the study itself.
CONTINUATION SHEET for either:
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STUDY NUMBER:
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CONTINUATION: page 6 of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
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P.A.: 09-25-0099
Genetic Testing
Some of the blood drawn from you as part of this study will be used for genetic tests. Genetic tests can help researchers
study how health or illness is passed on to you by your parents or from you to your children. Some things to consider in
thinking about whether or not to participate in these genetic studies include the possible effects on your emotional well
being. In other words, how might you feel about yourself and your life if you learn information about risks that could
affect your own health or that of your children? There may be no treatment for certain conditions and this may cause
some individuals to feel anxious, depressed, or stressed. Additional genetics counseling and advice is available from the
National Institutes of Health to help you understand the nature and implications of findings about you and your family.
Also, relationships with other family members may be affected by finding out risks they have but did not want to know.
An example would be if your children, brothers or sisters find out they have risks for health problems because of
information found out about you.
Some of the blood drawn from you as part of this study may be used for a test for HLA type, which is a genetic test of
markers of the immune system. It is usually used to match bone marrow or organ transplants. For research, HLA testing
might be used to try to identify factors associated with the progression of HIV disease or related conditions. In addition,
determining HLA type is necessary to be able to perform certain research studies. Some HLA types have been associated
with an increased risk of certain diseases like arthritis and other rheumatologic problems. However, simply having those
HLA types doesn’t mean you will develop these diseases.
Genetic testing can also be used to determine if people are directly related. These tests can reveal that a person’s
biological parents are someone other than their legal parents. If these facts were not known previously they could be
troubling to learn. It is our policy to not discuss such information unless it has direct medical or reproductive implications
for you or your family. By agreeing to participate in this study, you do not waive any rights that you may have regarding
access to and disclosure of your records. For further information on those rights, please contact Dr. Maldarelli, principal
investigator. Any genetic information collected or discovered about you or your family will be confidential. Medical
records containing this information will be kept under lock and key. We will not release any information about you or your
family to relatives, any insurance company, or employer unless you sign a release requesting us to do so. Genetic
information can be requested and obtained when a person applies for health insurance or a job and has signed a release.
Stored Samples and Future Research
Blood left over from this study will be stored. These stored samples will help us learn more about HIV, immune deficiency
or related conditions. In general, the research tests we perform are not like routine medical tests, and may not relate
directly to your medical care, so we may not put future test results in your medical record. However, if you wish,
someone on the study team will discuss the test results with you. We will not share these test results with your private
doctor unless you ask us to do so.
By agreeing to participate in this study, you do not waive any rights that you have regarding access to and disclosure of
your records. For further information on those rights, please contact Dr. Maldarelli.
Labeling of Stored Samples
We will label your stored samples with a code that only the study team can link to you. We will keep any information that
can be traced back to you private to the extent permitted by law.
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 7 of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
Future Studies
Other investigators may want to study your stored samples. If so, the NIH study team may send your samples to them,
along with a coded label. The study team may also share information such as your gender, age, health history, or
ethnicity. In some cases, an Institutional Review Board (IRB) will review new research proposals that would like to use
your samples. The IRB is a committee that oversees medical research studies to protect volunteers’ rights and welfare.
Investigators will only use your samples for research. We will not sell them. Future research that uses your samples may
lead to new products, but you will not receive payment for these products. Some future studies may need health
information (such as smoking history or present health status) that we don’t already have. If so, the NIH study team will
contact you for this information.
Benefits
In general, future research that uses your samples will not help you, but it may help us learn what causes AIDS, immune
deficiency, or related conditions. This research may also help us learn how to prevent or treat the condition.
Risks
The greatest risk is that someone may take information from your medical records without your permission. The chances
of this happening are very low. If this information becomes available, you may face discrimination when you apply for
insurance or a job. You may also have similar problems if you share the information yourself or let us release your
medical records.
Making Your Choice
If you agree to participate in this study, you agree to let us store your samples for future research. You also agree that
we can contact you again in the future. No matter what you decide, you may still participate in other studies at NIH.
However, your refusal to let us store your samples may lead to your withdrawal from this specific study. Even if you
agree now to let us store your samples, you can change your mind later. If you do, please contact us and say that you do
not want us to use your samples for future research.
MEDICAL RECORD
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
CONTINUATION: page 8 of 10 pages
PATIENT IDENTIFICATION
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
NIH-2514-3 (5-02)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
As part of your participation in this study, it will be necessary to test your blood for the presence of antibodies to the
Human Immunodeficiency Virus (HIV), the virus that causes Acquired Immune Deficiency Syndrome (AIDS). In order to
perform the test, a small amount of blood (approximately 2 teaspoons) will be withdrawn from one of your arms with a
needle. You may experience some slight discomfort at the needle entry site and there may be some bruising. In
addition, there is a very small risk of you fainting or of infection at the needle entry site. If your test results are found
to be positive, or if you are otherwise diagnosed as having AIDS, you should be aware of the following Clinical Center
HIV Testing Policy:
1.
Your physician will notify you promptly of the HIV test results.
2.
Your physician and/or the Clinical Center HIV counselor will offer you, and any current and/or ongoing
sexual partner(s) (spouses are generally considered to be current or ongoing sexual partners) or needle-sharing
partner(s) you identify, information on the meaning of the test results and how to prevent the spread of the
infection.
3.
Because the virus may be transmitted in several ways, it is important that you inform sexual and/or
needle-sharing partner(s) that any, or all, of them may have been exposed to the HIV virus and encourage
them to be tested. If you request it, staff at the Clinical Center will assist you in notifying your partner(s) and
arrange counseling for them through an HIV counselor.
4.
The results of your HIV test and/or documentation of the diagnosis of AIDS will become a part of your
Clinical Center medical record and, as such, will be protected from unauthorized disclosure by the Federal
Privacy Act of 1974. In general, access to your medical record will be restricted to those health care
professionals directly involved in your care or in the conduct of ongoing biomedical research, and information is
not usually released to other third parties without your permission or that of your designated representative.
However, there are some particular routine uses of such information of which you should be aware.
a. If you are unwilling or unable to notify your partner(s), the Clinical Center is responsible for
attempting to contact and inform them of their possible exposure to the virus. Reasonable attempts
will be made to protect your identity including withholding your name when notifying any partner(s) of
their possible exposure. Some notification or counseling of current and/or ongoing partners may be
carried out through arrangements with, or referral to, local public health agencies.
b. A summary of your care at the Clinical Center will be sent to the physician who referred you here for
treatment.
c. The Clinical Center may report certain communicable diseases, such as HIV infection, to appropriate
State and Federal government agencies.
i.
For Clinical Center patients who are Maryland residents, the Clinical Center reports by “Patient
Unique Identifier Number” (rather than by name) newly obtained HIV-positive results from its
laboratory to the Maryland Department of Health and Mental Hygiene. Patient Unique Identifier
Number is: last four digits of social security number, birth month, birth day, birth year, race and
gender.
MEDICAL RECORD
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
CONTINUATION: page 9 of 10 pages
PATIENT IDENTIFICATION
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
NIH-2514-3 (5-02)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
ii.
For Clinical Center patients who are Maryland residents, the Clinical Center reports by name new
cases of AIDS to the Maryland Department of Health and Mental Hygiene.
iii.
For Clinical Center patients who are not Maryland residents, the Clinical Center
reports HIV-positive results and/or AIDS to the patient’s primary care/referring physician.
If you have any questions regarding the HIV testing or the information provided above, you are encouraged to discuss
them with your physician and/or a Clinical Center HIV counselor: (301) 496-2381.
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
• Adult Patient or • Parent, for Minor Patient
STUDY NUMBER:
06-I-0197
CONTINUATION: page 10 of 10 pages
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY (Continuation Sheet)
• Adult Patient or • Parent, for Minor Patient
NIH-2514-1 (5-98)
P.A.: 09-25-0099
FAX TO: (301) 480-3126
File in Section 4: Protocol Consent
OTHER PERTINENT INFORMATION
1. Confidentiality. When results of an NIH research study are reported in medical journals or at scientific meetings,
the people who take part are not named and identified. In most cases, the NIH will not release any information about
your research involvement without your written permission. However, if you sign a release of information form, for
example, for an insurance company, the NIH will give the insurance company information from your medical record.
This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you
insurance.
The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the
Act allows release of some information from your medical record without your permission, for example, if it is required
by the Food and Drug Administration (FDA), members of Congress, law enforcement officials, or other authorized
people.
2. Policy Regarding Research-Related Injuries. The Clinical Center will provide short-term medical care for any
injury resulting from your participation in research here. In general, no long-term medical care or financial
compensation for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or
the Federal Government. However, you have the right to pursue legal remedy if you believe that your injury justifies
such action.
3. Payments. The amount of payment to research volunteers is guided by the National Institutes of Health policies.
In general, patients are not paid for taking part in research studies at the National Institutes of Health.
4. Problems or Questions. If you have any problems or questions about this study, or about your rights as a
research participant, or about any research-related injury, contact the Principal Investigator, Frank Maldarelli, M.D.
Building: 10, Room 12S245, Telephone: (301) 435-8019. Other investigators you may call are Rose McConnell (301)
443-5643.
You may also call the Clinical Center Patient Representative at 301-496-2626.
5. Consent Document. Please keep a copy of this document in case you want to read it again.
COMPLETE APPROPRIATE ITEM(S) BELOW:
A. Adult Patient’s Consent
B. Parent’s Permission for Minor Patient.
I have read the explanation about this study and have been given the
opportunity to discuss it and to ask questions. I hereby consent to take
part in this study.
I have read the explanation about this study and have been given the
opportunity to discuss it and to ask questions. I hereby give permission
for my child to take part in this study.
(Attach NIH 2514-2, Minor’s Assent, if applicable.)
Signature of Adult Patient/Legal Representative
Date
Signature of Parent(s)/Guardian
Date
C. Child’s Verbal Assent (If Applicable)
The information in the above consent was described to my child and my child agrees to participate in the study.
Signature of Parent(s)/Guardian
Date
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE
FROM APRIL 14, 2008 THROUGH APRIL 13, 2009.
Signature of Investigator
Date
Signature of Witness
Date
Prot_SAP_000.pdf:
Version 5.2
September 20, 2007
A RANDOMIZED PLACEBO CONTROLLED TRIAL OF ATORVASTATIN IN HIV
POSITIVE PATIENTS NOT ON ANTIRETROVIRAL MEDICATIONS WITH THE
SPECIFIC AIMS OF STUDYING THE EFFECTS OF ATORVASTATIN ON HIV
VIRAL LOAD AND IMMUNE ACTIVATION MARKERS
Sponsored by: National Institute of Allergy and Infectious Diseases
NON-IND Protocol
Version 5.2
Principal Investigator:
Anuradha Ganesan (NNMC)
Associate Investigators:
Frank Maldarelli, Timothy Whitman (NNMC), Catherine Decker (NNMC), Nancy Crum-
Cianflone (NMCSD), Mary Bavaro (NMCSD)
Research Study Coordinator:
Sean McCarthy (NNMC)
Carolyn Brandt (NMCSD)
Version 5.2
September 20, 2007
2
TABLE OF CONTENTS
Page
SITES PARTICIPATING IN THE MAIN STUDY....................................................................... 4
1.0 PRECIS............................................................................................................................... 5
2.0
BACKGROUND............................................................................................................7-11
2.1
HIV structure and replication...................................................................................7
2.2
Potential antiretroviral targets..................................................................................8
2.3 Host and viral factors in HIV assembly, budding and release..............................8,9
2.4
Statins and their putative effects on viral replication and T cell activation……...10
2.5
Statin effects on HIV-1 RNA levels in vivo...........................................................10
3.0
OBJECTIVES....................................................................................................................12
Primary objective...............................................................................................................12
Secondary objective...........................................................................................................12
4.0
STUDY DESIGN…………………………………………………………………….12, 13
5.0
SELECTION AND ENROLLMENT OF SUBJECTS................................................ 13-20
5.1
Inclusion Criteria ...................................................................................................13
5.2
Exclusion Criteria ..................................................................................................15
5.3
Study Enrollment Procedure overview............................................................…. 16
5.3.1 Prerandomization evaluations................................................................................17
5.3.2 Randomization scheme..........................................................................................17
5.3.3 Study entry……………………………………………………………………….18
5.3.4 On study evaluations………………………………………………………......... 18
5.3.5 Post treatment evaluation………………………………………………………...19
5.4 Criteria for withdrawal……………………………………………………............20
5.5
Breaking the blind………………………………………………………………..22
5.6
Criteria for stopping enrollment………………………………………………….22
6.0
STUDY TREATMENT............................................................................................... 22-24
6.1
Atorvastatin............................................................................................................22
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3
6.2
Product Supply, Distribution, and Pharmacy.........................................................24
6.3
Drug Storage..........................................................................................................24
6.4
Accountability of drugs..........................................................................................24
7.0
STATISTICAL CONSIDERATIONS…..………………………………………….........25
8.0
DATA COLLECTION AND MONITORING AND ADVERSE EXPERIENCE
REPORTING…………………………………………………………………………27-30
8.1
Adverse and serious adverse reporting ..................................................................27
8.1.1 Definition...............................................................................................................27
8.1.2 Reporting................................................................................................................27
8.2
Protocol monitoring and DSMB............................................................................29
8.3 Data and Safety Monitoring Plan………………………………………………...30
8.4 Data Management Plan…………………………………………………………..30
9.0
HUMAN SUBJECTS………………………………………………...………………31-34
9.1
Benefits ..................................................................................................................31
9.2
Risks.......................................................................................................................31
9.2.1 Medication associated risk…………………………………………………….....31
9.2.2 Risks associated with hypercholesterolemia……………………………………..32
9.2.3 Risks associated with phlebotomy………………………………………………33
9.3
Confidentiality…………………………………………………………………...33
9.4
Study discontinuation…………………………………………………………….33
9.5 Sample Storage…………………………………………………………………..33
10.0 REFERENCES……………………………………………………………………….35-37
APPENDICES
APPENDIX I: DAIDS Toxicity Tables
APPENDIX I.A: CPK Toxicity Criteria
APPENDIX II: Drug interactions with atorvastatin
Version 5.2
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4
APPENDIX III: Package insert for atorvastatin
APPENDIX IV: Piper Fatigue Scale
APPENDIX V: Becks Depression Inventory
SITES PARTICIPATING IN THE MAIN STUDY
National Institutes of Health
National Naval Medical Center
Naval Medical Center San-Diego
Version 5.2
September 20, 2007
5
1.0 PRECIS
This protocol is a randomized, double blind, placebo controlled trial designed to study the
effects of the lipid lowering statin, atorvastatin on HIV-1 viremia.
Untreated HIV-1 infection results in an incurable, progressive immunodeficiency and
death, usually from opportunistic infections. Combination antiretroviral therapy (ARV) has been
successful in suppressing HIV replication and reducing morbidity and mortality. [1] Long term
ARV therapy is associated with the development of HIV-1 drug resistance, and significant
adverse side effects including metabolic and cardiovascular complications. [2] Prolonged therapy
with certain antiretrovirals is associated with increased risk of cardiovascular disease and a
number of dyslipidemic syndromes, including increased levels of cholesterol, LDL, and
triglycerides in peripheral blood. [3] New therapeutic strategies to suppress HIV-1 infection are
essential.
Previously, in vitro studies suggested that exposure to cholesterol-lowering statins results
in decreases in HIV-1 replication.[4, 5] The mechanisms of inhibition remain uncertain, but
possibilities include disrupting membrane trafficking or cytoskeletal processes necessary for
intracellular transport of viral proteins, or altering cellular activation state necessary for viral
gene expression.[4-8] Initial in vivo studies of the effects of statins on HIV-1 have been largely
anecdotal in nature and have yielded conflicting results. [9-12] Although statin therapy is
commonly used in HIV-1 infection, adverse effects from the combination of antiretrovirals and
statins are possible.[13] A more thorough understanding of the effects of statins on HIV-1
replication is essential to determine the potential therapeutic effect and to investigate the risks
and benefits of this approach in vivo.
We plan to conduct a double blind randomized placebo controlled trial, with a cross over
design, to study the effects of atorvastatin in 22 HIV-infected patients not currently taking
antiretroviral therapy. Patients will be randomized to receive either placebo or atorvastatin 80mg
for 8 weeks. After a 4 week wash out period patients on the atorvastatin arm will crossover to
placebo and vice versa patients in the placebo arm will cross over to atorvastatin for an
additional 8 weeks. Upon completion of study medications all patients will be followed for 4
weeks. Each arm will have a minimum of 11 patients each. The primary outcome measure in this
study is the effect of lipid lowering agents on HIV-1 RNA levels; additional secondary outcome
Version 5.2
September 20, 2007
6
measures include effects of lipid lowering agents on lipid profile, markers of inflammation and
immune activation and investigations of host and viral genetic factors.
Version 5.2
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7
2.0 BACKGROUND
2.1 HIV structure and replication
HIV-1 is a member of the lentivirus family of retroviruses, a group of enveloped RNA
viruses that replicate via a DNA intermediate. The HIV genome is composed of genes that code
for structural components, enzymes necessary for viral replication, as well as regulatory and
accessory proteins. Steps in HIV-1 replication depicted in figure 1 include viral binding and
interaction with chemokine receptors (1), membrane fusion, (2) viral uncoating (3) and reverse
transcription of viral RNA (4). The pre-integration complex is then transported to the nucleus
where viral DNA integrates into the host cell chromosome (5) followed by viral RNA synthesis
(6). The later steps include translation of viral mRNA into viral proteins, virion processing,
assembly, (7) maturation followed by budding and release (8).
Figure 1 - Schematic representation of HIV-1 replication (adapted from the article by
Peterlin and Trono [14])
2
3
4
5
6
7
8
1
Version 5.2
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8
2.2- Potential antiretroviral targets
Initially, antiretroviral therapy was concentrated exclusively on viral targets and focused
on available inhibitors of viral enzymes reverse transcriptase and protease (Steps 4, and 7,
respectively) or the viral fusion reaction (Step 1). Newer approaches include targeting
interactions between host and viral factors, including inhibiting virion binding to susceptible
cells with HIV-1 coreceptor inhibitors.[15] HIV populations in vivo are genetically diverse, and
one effect of drug therapy is selection of viral mutants that are resistant to antiretrovirals.
Emergence of drug resistance is one of the most critical factors limiting long term suppression of
HIV replication. New therapeutic strategies to limit HIV replication are essential. One such
approach is to target cellular processes that are essential for virus replication in such a way that
virus replication is inhibited without causing critical damage to cellular functions. In one
potential example of this approach, several investigators have reported that statin therapy may
inhibit HIV-1 replication in vitro, either by interfering with intracellular transport or cellular
activation pathways, resulting in marked reductions in HIV replication without significant
cellular injury.[4-8] In vivo data evaluating this approach are lacking, and we propose to
investigate the effects of statin therapy on HIV-1 replication in chronically infected individuals.
2.3 Host and viral factors in HIV assembly, budding and release
HIV virion maturation is a complex process requiring interactions between the host and
the virus. One critical step in virus replication, virion assembly, requires specific host virion
interactions. Virion components are transported to the cell surface using specific lipid “rafts”,
cholesterol-rich cellular micro domains and bud through cell membranes by co-opting the
multivesicular body (MVB) process that normally functions to recycle plasma membrane
components.[16] [17] Transport via rafts is a highly specialized process that requires specific
protein protein interactions; for HIV-1 transport is thought to involve both cellular and viral gene
products.
Host pathways involved in transport and budding include a series of membrane- protein
complexes which bind target proteins and ensure targeting to specific intracellular locations. A
number of cellular proteins have been identified that participate in intracellular trafficking,
including TSG101, a lipid raft constituent, which binds specific protein domains ensuring
transport.
Version 5.2
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9
HIV-1 viral genes involved in transport are products of the HIV-1 gag gene. Gag is
synthesized as a polypeptide precursor molecule composed of several proteins including Matrix
(p17), Nucleocapsid (p7), Capsid (p24), p6, p1, p2 and a spacer protein. Expression of gag
proteins appears sufficient for the assembly and release of non-infectious virion like particles.
[18-20] The gag precursor, referred to as pr55gag, is composed of several domains that play
specific roles in viral assembly and release. These domains include the membrane binding
domain that directs virus to the membrane (M), the multimerization domain that promotes gag -
gag multimerization (I) and the late domain (L) that is involved in viral budding. [21] A
specific HIV-1 Gag protein, denoted p6, may provide a critical link between cellular machinery
and virion component. P6 has a specific proline-threonine-alanine-proline (PTAP) domain that is
thought to define the L domain and interact directly with cellular protein TSG101. [22, 23] The
P6-TSG101 interact may represent the docking mechanism by which virion components are
loaded onto lipid rafts. Notably, in vitro investigations studying the effects of mutations in p6
resulted in marked decreases in HIV-1 production.[24] Similarly, depletion and overexpression
of cellular TSG 101 inhibits viral budding.[25, 26] Recently Carrington et al investigated the
hypothesis that TSG101 may have naturally occurring variants in the human population, and that
these variants may influence circulating levels of HIV-1. Interestingly, TSG 101 polymorphisms
in this study appeared to have a strong association with disease progression over time
(Carrington M, in preparation). In addition, analysis of genetic polymorphisms in the Swiss
Cohort, a large natural history study of HIV-1 infected patients in Europe revealed an association
between TSG101 genotype and disease progression .[27] These data suggest that interactions
between TSG 101 and HIV may have significant clinical consequences. The virion transport
mechanism using lipid rafts may represent an attractive therapeutic target. In addition to proteins
such as TSG101, lipid rafts contain large amounts of cholesterol. Disruption of lipid rafts by
depleting cellular cholesterol using either methyl beta cyclodextrin or the statin simvastatin
results in marked reduction in HIV virion production. Furthermore the virion particles produced
are not as infectious as wild type virus.[4] This suggests that lipid rafts play a critical role in
HIV-1 replication and may be potential therapeutic targets for control of HIV viral replication.
Version 5.2
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10
2.4- Statins and their putative effects on viral replication and T cell activation
Disruption of lipid rafts may not be the only mechanism by which statins might alter viral
replication. Statin drugs are competitive inhibitors of the enzyme HMG CoA reductase. This
enzyme catalyzes the conversion of HMG CoA (3-hydroxy 3 methylglutaryl-coenzymeA) to
mevalonate, the rate limiting step in cholesterol synthesis. By limiting synthesis of mevalonate,
statins inhibit the synthesis of not just cholesterol but also of non–steroidal isoprenoid
derivatives. Non-steroidal isoprenoid compounds are involved in the post-translational
modification of several cell proteins including the Rho and Rac GTPases.
The Rho family of GTPases, this family includes Rac GTPases, control actin
cytoskeleton remodeling in response to stimuli.[28] HIV entry into cells is an actin dependent
process.[6] It is believed that interactions between HIV env, CD4, and its co receptors activate
Rac-1 GTPase. This stimulates actin filament reorganization, which is needed for HIV fusion.[7]
By blocking mevalonate synthesis, statins prevent the functioning of Rho GTPases and actin
cytoskeleton remodeling. [29] Recently published data suggest that by targeting the function of
Rho GTPases statins inhibit HIV-infection of SCID mice grafted with adult human PBMCs.[11]
T cell activation plays an important role in HIV progression. Depletion of CD4 positive
cells during HIV infection is not merely a consequence of direct infection of these cells. T cell
activation leads to T cell proliferation T cell depletion and ensuing immunosupression. [30]
Statins alter T cell activation and may affect disease progression in HIV infected patients.
Statins may affect T cell activation via several mechanisms including altering MHC II
expression and lipid rafts disruption. T cell receptors localize within lipid rafts and disruption of
lipid rafts leads to altered T cell activation. [31] [32]
2.5 Statin effects on HIV-1 RNA levels in vivo
In vivo data on statin use in HIV infection is limited. In a study of 6 early stage (CDC
stage A1), ARV naïve patients with stable viral loads, treated with lovastatin, plasma viral load
decreased with statin use. The reductions in viral load in this group of patients were between 0.2
and 1.3 log10 copies. Viral loads done 12 weeks after Lovastatin discontinuation demonstrated a
viral rebound, with 5 of the 6 patients demonstrating a change in their set point. This study was
non-randomized and did not study viral RNA levels in patients not treated with statins[11]. In a
recent report, we reported analysis of patients treated with 40 mg Pravastatin as part of a study of
Version 5.2
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11
endothelial function. Seven patients in this study had detectable viremia allowing the authors to
analyze the effects of Pravastatin 40 mg on viral load. 3/7 patients had a decrease in viral load
while 4/7 had increases. We concluded that there appeared to be no significant effect of statin
therapy on HIV-1 viral RNA levels in this group. Interestingly, however, 3/7 patients had
rebound in viral load after discontinuation of Pravastatin.[12] Two additional studies have also
failed to show any effect of statin therapy on HIV-1 viral RNA levels. In a retrospective study
patients who started “first line HAART’ were compared with those who started ‘first line
HAART” and were at some point thereafter started on statins. In this study the 2 groups did not
differ in the number of patients who had viral rebound after initial suppression to less than 500
copies/ml or blips (defined in this study as a decline in viral load to <500 copies followed by a
rebound to greater than 500 copies/ml and then a fall to <500 copies).[10] Finally, chronically
infected patients who had discontinued antiviral therapy for 12 weeks were studied by examining
the effects of Simvastatin (80mg) on HIV-1 RNA. No decreases in viral RNA were detected after
4, 8 and 12 weeks.[9] The results of this study are difficult to interpret given the missing data
points.
There may be numerous reasons for the inconsistent effect of statin exposure on HIV-1
viral RNA levels; statins may be effective with certain strains of HIV-1 or with specific
combinations of TSG101/p6 genotypes. Effects may not be manifest or may be blunted in
patients with elevated cholesterol levels at baseline, where statin induced decreases may not
sufficiently decrease intracellular cholesterol levels sufficiently to affect HIV replication. The
lack of a rigorous study design for most of these studies may introduce sufficient bias to prevent
clear cut results.
The 3 statins tested thus far in vivo models are pravastatin, lovastatin and simvastatin.
Pravastatin is the only statin that does not have significant drug- drug interactions in HIV
positive patients on antiretrovirals. However, pravastatin use is associated with modest decreases
in serum cholesterol, as the decreases in serum cholesterol seen with pravastatin use may not be
sufficient to result in lipid raft disruptions necessary to demonstrate any significant antiviral
effects. Both simvastatin and lovastatin use is associated with significant decreases in serum
cholesterol but both drugs are contraindicated with other antiretrovirals. Atorvastatin use is
associated with significant reductions in serum cholesterol, and several reports suggest that the
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12
use of atorvastatin while theoretically contraindicated with antiretrovirals is safe and well
tolerated. Given this we chose to study atorvastatin for its antiviral effects.
To further define the effects of statins on HIV viremia and to study virus host interactions
in the context of statin use we have designed a randomized placebo controlled cross over study
of atorvastatin use in HIV positive patients. In this study the effects of cholesterol reduction on
HIV-1 viremia, T cell activation, and metabolic parameters in HIV positive patients will be
explored. Furthermore viral and host genetic factors as it relates to response or lack of response
to statins will also be explored.
3.0 OBJECTIVES
3.1 Primary objective
The primary objective of this study is to compare the changes in HIV-1 viral load during
the atorvastatin phase with the changes in viral load in the placebo phase.
3.2 Secondary objectives
• To compare the changes in the expression of immune activation markers between the
placebo phase and the atorvastatin phase.
• To investigate HIV-1 and TSG 101 phenotypes among enrollees
• To investigate the changes in the metabolic profile between the placebo and the
atorvastatin phase
• To investigate the safety profile of atorvastatin in HIV positive patients not on
antiretroviral therapy
• To compare the subjective and objective evaluation of fatigue during the atorvastatin and
placebo phase
4.0 STUDY DESIGN
Study design
This study utilizes a case cross over design to investigate the effects of atorvastatin on
HIV viral load, immune activation markers and metabolic profile. Figure 2 is a diagrammatic
representation of the study design. A double blind strategy was chosen for the design of this trial.
In general statin therapy is associated with a number of side effects, some of which, including
Version 5.2
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13
fatigue and muscle aches may be highly subjective or multifactorial in origin. If statins do show
an antiviral effect, then their use will be balanced by well described adverse effects. We wish to
evaluate such adverse effects in detail in patients enrolled in the trial, and feel double blind
approach is the most rigorous and objective.
HIV positive patients, who have been off anti-retroviral medications for a minimum of 3
months and with no documented evidence of resistance, will be recruited for this study. Each
subject will have 3 baseline viral loads and will be randomized to receive either 80 mg of
atorvastatin or placebo for 8 weeks. Following this, there will be a 4 week wash out phase. Upon
completion of the wash out phase patients who were initially on the atorvastatin arm will switch
to the placebo arm, while patients who started in the placebo arm will switch to atorvastatin to
complete an additional 8 weeks. All patients will be followed for 4 more weeks upon
completion of study medications. The study design is schematically represented in Figure 2.
Atorvastatin 80
Placebo
Wash out
Atorvastatin 80
Placebo
0
8
12
20
24
Figure 2 - Graphical representation of the study design (time represented
in weeks)
Follow up
5.0 SELECTION AND ENROLLMENT OF SUBJECTS
5.1 Inclusion Criteria
Establish with patient prior to Informed Consent:
• Adults 18 years of age or older
• HIV-1 infection, as documented by a licensed ELISA test kit and confirmed by a
Western blot assay at any time point prior to study entry or at study entry ( May do
after informed consent if no test results are available).
Version 5.2
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14
Off all ARV for ≥ three months prior to study entry, no documented evidence of viral resistance,
and no evidence of acute HIV infection. For the purposes of this study acute HIV infection will
be defined as presence of a detectable HIV-1 viral RNA in the presence of a non reactive HIV-1
or HIV-2 antibody assay or an indeterminate western blot. For the purposes of this study viral
resistance is being defined as having a genotypic or phenotypic evidence of resistance or in the
absence of formal resistance testing clinical evidence of resistance for e.g. patients with
persistent viremia in the face of adequate adherence
• Willingness to use a method of contraception during the study period. Adequate
methods of birth control include: condoms, male or female, with or without a
spermicide; diaphragm or cervical cap with spermicide; intrauterine device; any of
the methods that require a prescription (such as contraceptive pills or patch, Norplant,
Depo-Provera, and others) or a male partner who has previously undergone a
vasectomy,
• Willingness to have blood drawn
• Non known allergy or contraindication to atorvastatin use
• Ability to understand and willingness to sign the informed consent
• Willingness to have blood stored for future phenotyping and genotyping
After Informed Consent:
• CD4 cell count greater than 350 cells/ml
• 3 viral loads that average greater than 1000 copies/ml within a 4 week period.
• The viral loads will be done using the bDNA method in the NIH laboratory and must
be within 20% (log10bDNA of each other).
• A fasting total cholesterol lower than 240mg/dl and a LDL cholesterol lower than
130mg/dl
• Liver function tests (AST or ALT) not greater than 1.5 times the upper limit of
normal. Evidence of active hepatitis B or C will not be considered an exclusion
criteria if the liver function tests are within normal limits.
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• Creatine phosphokinase elevations (CPK) not greater than 3 times the upper limit of
normal (ULN) on two sequential determinations and, in the opinion of the
investigator, without clear association with exercise.
• Laboratory values:
Absolute neutrophil count (ANC) ≥ 1000/mm3.
Hemoglobin ≥ 11.0 g/dL.
Platelet count ≥ 100,000/mm3
Creatinine ≤ 2 x ULN
Serum amylase and lipase ≤ 1.25 x ULN
• Negative serum pregnancy test at randomization
5.2 Exclusion Criteria
• Pregnancy or breast feeding
• Active drug use or alcohol abuse/dependence, which in the opinion of the
investigators will interfere with the patient’s ability to participate in the study
• Serious illness requiring systemic treatment and/or hospitalization within 30 days of
entry
• Evidence of active opportunistic infections or neoplasms that require chemotherapy
during the study period except cutaneous Kaposi Sarcoma
• Allergy or hypersensitivity to atorvastatin or any of its components
• History of myositis or rhabdomyolysis with use of any statins
• History of inflammatory muscle disease such as poly or dermatomyositis
• Concomitant use of fibric acid derivatives or other lipid lowering agents including
patients on statins and Ezetimibe
• Concomitant use of drugs that have significant interactions with atorvastatin. Please
see appendix II for a listing,
• Concomitant use of St.Johns wort
• Concomitant use of Valproic acid
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• Patients who are on concurrent immunomodulatory agents, including systemic
corticosteroids will be ineligible for 3 months after completion of therapy with the
immunomodulating agents. Topical, nasal or inhaled corticosteroids use is not an
exclusion criteria
• Serum LDL cholesterol less than 40 mg/dl
• Vaccinations within 6 weeks of study entry.
5.3 Study enrollment procedure overview
Prior to implementation of this protocol, sites must have the protocol and informed
consent forms approved by their local institutional review board (IRB). Health care providers at
participating institutions will identify eligible patients. At the National Naval Medical Centers all
providers and research nurses at the Infectious Disease Clinic (IDSI) will identify eligible
patients. Once a candidate for study entry is identified, patients will be approached by their
providers or research nurses about the protocol. If the candidate is interested details of the
protocol will be reviewed with the candidate by the study PI/designee. If the volunteer is willing
to participate in the study, they will be provided with copies of the informed consent to review.
After all questions, about the study and the informed consent, have been answered to the
participant’s satisfaction, they will be asked to sign the IRB approved consent form.
Volunteers enrolled at the NIH will be required to sign a screening consent to undergo
screening laboratories for the study. Patients who satisfy inclusion criteria and are willing to
participate in the study will be required to sign the study informed consent. Since study
participants at NNMC receive their routine care at NNMC screening consents will not be used at
the NNMC prior to study enrollment. Volunteers at NNMC will be required to sign the study
consent only.
It is anticipated that most subjects will have their routine immunizations prior to signing
informed consent. However, in the event routine vaccination is required after the subject has
been randomized; for DOD sites (NNMC and NMCSD) we will attempt to vaccinate the
individual after completion of the week 8 visit or at the end of the study phase of the protocol.
For subjects vaccinated during the wash-out phase or at the end of the study the wash-out phase
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or the last study visit will be extended by 2 weeks. For patients seen at the NIH site, the protocol
will not administer routine vaccinations, with the exception of the influenza vaccination. It is
anticipated for some patients, participation may overlap with influenza season and that influenza
vaccination will be necessary in the event that protocol participation begins prior to but extends
into, influenza season. For such patients, standard, inactivated influenza vaccination will be
administered (if necessary) during the week 8 visit. For subjects vaccinated during the wash-out
phase or at the end of the study the wash-out phase or the last study visit will be extended by 2
weeks. Extension of both these study phases is necessary because of the effects of vaccination on
viral kinetics.[33]
Definitions for Schedule of Events – Timing of Evaluations
5.3.1 Prerandomization evaluations
After signing either the screening/study informed consent, patients will undergo
screening tests. Screening will include a complete medical history and physical examination.
Laboratory testing will include a fasting lipid profile, flow studies (FACS), routine safety labs
which will include a liver function test and creatinine kinase assay, a hepatitis profile and viral
load assay to establish baseline viral load. Due to the variability in the viral load assay, we will
utilize a minimum of 3 viral load assays to establish a baseline. All testing will need to be
completed within a 4 week period prior to randomization. During this period, patients may come
in for testing at their own convenience, but testing will not be done more than once within a 24
hour period. All laboratory tests except standard safety labs will be done centrally at SAIC
Frederick to maintain consistency. Volunteers at the NIH who satisfy the inclusion criteria and
who continue to be interested in the protocol will be now required to sign the study consent.
5.3.2 Randomization scheme
Subjects will be randomized after the investigators have ascertained that the subject
meets criteria for inclusion. Prior to randomization investigators will ensure that the patient
understands the risks and benefits associated with the study and informed consent has been
signed. Randomization will be done using a random number table generated by the NIH
pharmacy department. 11 patients will be randomized to the placebo arm of the study and 11 to
the drug arm of the study initially. The 11 patients randomized to placebo will then cross over
after completion of 12 weeks on study (8 weeks on study treatment and 4 weeks wash out) to the
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study arm and vice versa patients in the atorvastatin arm will cross over the placebo arm after 12
weeks on study
5.3.3 Study entry
On the day patients get randomized, patients will undergo routine safety labs including
liver function tests (LFT), creatinine phosphokinase, hematological parameters, fasting lipids
including apolipoprotein B, hsCRP, plasma HIV viral load and a full FACS. Patients will also
have a sample of blood stored for future phenotyping and genotyping. Patients will be required to
answer both the Piper Fatigue Scale and the Beck Depression Inventory.
5.3.4 On study evaluations
Efficacy Assessments
Patients will undergo HIV BDNA assays on days 7, 14, 42, 56, 84, 91, 98, 126, 140 and
168. Patients will also undergo evaluation for immune activation markers levels specifically
CD38 and HLA-DR expression on CD4 and CD8 cells and Ki67 will be done on days 7, 56, 84,
91, 140 and 168. Fasting lipids, apolipoprotein and ultrasensitive hsCRP will be done at
randomization and on day 7, 56, 84, 91, 140 and 168. All testing other than standard safety
testing will be done at SAIC Frederick. The Beck depression inventory and the Piper fatigue
scale will be administered on days 56, 84, 140 and 168.
Safety assessments
Safety assessments will be done at specified study visits and will include clinical
assessment, physical exam, medication assessment, routine chemistry and hematology, serum
creatinine phosphokinase, liver function tests, and serum pregnancy tests. The Piper Fatigue
Scale will be administered prior to and following each arm. Please see table 1 for details. All
safety labs will be done at the individual institutions. All laboratories performing study related
tests are CLIA certified laboratories
Genetic studies
TSG 101 genotyping and HLA typing will be performed. Additional genotyping of
specific host genes will be performed as indicated. Additional blood will be obtained as indicated
for storage and future use.
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Adherence assessment
Pill counts will be performed at each visit to monitor adherence to the protocol, and
patients will be asked about adherence.
5.3.5 Post treatment evaluations
4 weeks after treatment discontinuation (± 1 week), patients will have repeat viral load,
lymphocyte sub set analysis, immune activation parameters, safety labs including LFTs and
creatinine phosphokinase. All visits will be completed on the indicated days of the protocol, for
unforeseeable circumstances that might render the patient unable to complete the study visit on
the designated days the patient may reschedule within a 2-5 day window except for the end of
study visit which may be completed within a 1 week window.
5.4 Subjects can be discontinued from the study for the following reasons:
• Failure to comply with the protocol
• If they develop a serious adverse event (SAE)
• Pregnancy, if a patient becomes pregnant on study; she will stop the study drug and be
followed as part of the study through the pregnancy including the peri-partum period to
ensure her safety.
• Any subject with a creatinine phosphokinase (CPK) value greater than 10 times the
upper limit of normal (i.e grade 3 or higher), will undergo repeat testing. Repeat
testing will be conducted at protocol specified time points (i.e. within 1-3 days of the
initial result and also at day 7). Persistently elevated laboratory values, i.e. CPK
measurements that remain at the same level or are higher than the initial value, on
three consecutive determinations, despite cessation of exercise will result in study
drug discontinuation.
• In addition, all CPK elevations associated with grade 3 or higher symptoms or for
significant symptoms or elevations in CPK that do not fall into either of the above
mentioned categories; a conference call with representatives from all three
participating sites (either the PI or their designee) will be initiated. Decisions
regarding study drug discontinuation for patients meeting the above listed criteria
will be made on an individual case by case basis. The medical monitor at the sites
will be involved in all decisions regarding study drug discontinuation.
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• Patient develops liver function elevations 3 times the upper limit of normal
• If the serum LDL cholesterol falls to less than 40mg/dl
• Develops a grade 2 or greater allergic reaction to the medicine or develops signs and
symptoms of an immediate hypersensitivity reaction to the medication
• Patient needs to start antiretroviral agents using current DHHS guidelines as
recommendations.
• Patient develops any condition that the study investigators deem would be detrimental for
the patient to continue on the study
• If the patient desires to leave the study
• Patient starts taking other lipid lowering drugs including fibric acid derivatives, bile acid
sequestrants and niacin preparations
• Patients will be dropped from the study if their CD4 count drops by fifty percent on two
successive determinations, or falls below 250 cells/µl in the absence of any documented
ongoing infections/inflammatory processes while on study
If subjects are discontinued from the study secondary to any of the above given reasons they will
be replaced according to the prior randomization.
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CLINICAL AND LABORATORY EVALUATION
• * Study consent will be signed at NNMC prior to screening and at randomization at the
NIH
• † In the event subject is vaccinated these visits will be extended by 2 weeks
Table 1- Schedule of events
Evaluation*
Screening
Randomization
D7
W1
D14
W2
D42
W6
D56
W8
D84†
W12
D91
W13
D98
W14
D126
W18
D140
†
W20
D168
W24
Documentation of
HIV
Pos ELISA
and
Confirmatory
Blot, previous
results will be
allowed
Medical
/Medication
history
Nadir CD4
Clinical
Assessment
Questionnaires
Physical Exam
Hepatitis profile
Fasting lipid
profile
Markers of
inflammation
Hematology
Chemistry
including CK
Liver Function
Tests
Urinalysis
Pregnancy Testing
Full FACs
HIV viral load
(bdna)
(3 viral load
measures will
be used to
establish
baseline)
Statin/placebo
Stored
Plasma/PBMC
Stored Sera
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5.5 Breaking the blind
In the event of a medical emergency or in the event an off study criterion is met where
knowledge of the treatment will affect medical management, the investigators after consulting
with the medical monitor can break the blind. To break the blind investigators will contact the
pharmacy department by pager and via electronic mail, as they will hold the randomization code.
In the rare event of such an occurrence the process will be documented in writing. If the
DSMB decides to terminate the study, the blind will be broken and study participants and their
primary physicians will be informed of their drug assignments.
5.6 Criteria for Stopping Enrollment
Once patient enrollment is completed the study will be closed for further enrollment or if
the DSMB decides to terminate the study prior to complete enrollment. The DSMB will meet
after half the participants in the clinical trial have completed the study. Alternatively they will
also convene if two study patients have grade III or higher adverse events that in the opinion of
the investigator are definitely, possibly or probably associated with the drug. Please note: unlike
other lab AE’s that would necessitate convening a DSMB if 2 subjects have a grade 3 or higher adverse
event, the DSMB would convene only if the grade 3 CPK elevations are persistent.
6.0 STUDY TREATMENT
STUDY DRUG
6.1 Atorvastatin
Metabolism and mechanism of action
Atorvastatin calcium belongs to a group of lipid lowering agents referred to as statins.
Atorvastatin is a selective competitive inhibitor of the enzyme 3 hydroxy-3methylglutaryl
coenzyme A (HMG CoA reductase). This enzyme catalyzes the conversion of HMG CoA to
mevalonic acid, the rate- limiting step in cholesterol biosynthesis. This class of drugs have been
utilized in both the primary and the secondary prevention of coronary artery disease (CAD) [34]
[35] [36].
Atorvastatin is orally administered and is well tolerated. Atorvastatin is metabolized by
the cytochrome P450 3A4 system to ortho and para hydroxylated metabolites. Atorvastatin and
its metabolites are primarily hepatically excreted [37]. The metabolism of atorvastatin may be
influenced by CYP 3A4 inducers and inhibitors.
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Adverse effects of Atorvastatin
The most common side effects associated with atorvastatin use are gastrointestinal. In
clinical trials the following events were reported as per the package insert in greater than 2% of
the cases: chest pain, nausea, bronchitis, rhinitis, arthritis, insomnia and dizziness, urinary tract
infection and peripheral edema.
Atorvastatin and effects on liver enzymes
Persistent elevations in liver enzyme to 3 times the ULN have been reported in 0.2-2.3%
of patients studied on clinical trials of atorvastatin. Upon discontinuation of the drug these
elevations are reversible. Fatal liver injury has been reported with atorvastatin use [38]. Overall it
appears that fatal liver injury is a rare event in patients using statins. Liver function abnormalities
associated with atorvastatin use are seen at all doses. However, the incidence of these
abnormalities is greater with higher doses of the drug.
In a recently reported study of secondary prevention of CAD, 10,001 patients were
randomized to receive either10 or 80 mg of atorvastatin. In this study persistent elevation in liver
enzymes were seen in less than 1% of all patients, however the incidence was significantly
higher in the 80 mg subgroup (1.2% vs 0.2%). [39]
The package insert states that the use of atorvastatin is not recommended in patients with
active liver disease. Serial monitoring of liver function tests prior to start of drug, 6 to 12 weeks
after and semi annually thereafter is advised by the drug manufacturers. More stringent
monitoring at shorter intervals will be done as part of this protocol.
Atorvastatin and myopathy
Myalgia and rhabdomyolysis have been reported with atorvastatin use. In the ASCOT
study there was a single case of non-fatal rhabdomyolysis among 5168 patients randomized to
atorvastatin. [40] In a study of secondary prevention of CAD, among 10,000 patients
randomized to receive either 10 or 80 mg of atorvastatin there were 5 cases of
rhabdomyolysis.[39] While rhabdomyolysis is a complication of atorvastatin it appears
relatively rare.
The risk of myopathy is increased when atorvastatin is used in conjunction with azole
antifungals, erythromycin, clarithromycin, niacin, fibric acid derivatives or cyclosporine [37].
Patients who use fibric acid derivatives, niacin and cyclosporine will not be enrolled into the
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study. Patients who start azoles or erythromycin or clarithromycin while on study will be
monitored closely for signs and symptoms of myopathy, patients on these drugs at the time of
enrollment will not be eligible for this study until completion of therapy with these agents.
In addition the risk of myopathy is increased with the concomitant use of grape fruit juice
and atorvastatin. These interactions are mediated via the cytochrome p 450 system; grape fruit
juice is an inhibitor of this system [41] While on study patient will be advised to avoid grape
fruit juice and grape fruit.
To reduce risk to our study patients we will monitor liver function (LFT) and creatinine
phosphokinase (CPK) at baseline and as indicated in the schedule of events. Patients will also be
questioned about myalgia or weakness at each visit. Presence of any of these symptoms will
require complete evaluation as judged suitable by their health care provider. Patients who
participate in this study will be asked to refrain from vigorous exercise regimens for the study
period. Vigorous exercise is known to increase CPK levels and may cause patients to be
unnecessarily excluded /withdrawn from the study.
• Pregnancy and breast feeding are contraindications for atorvastatin use; atorvastatin is
classified as a pregnancy category X drug. Pregnant or nursing women will not be
enrolled in this study and patients will be required to use reliable methods of
contraception to be enrolled in this study. If a patient becomes pregnant on study, she will
be asked to stop taking study drug and will be followed through her pregnancy and the
peripartum period.
6.2 Product Supply, Distribution, and Pharmacy
Both drugs (i.e. atorvastatin and Placebo) will be formulated by the NIH PDS and will be
supplied to both the sites. Both placebo and drug will be identical in appearance. They will be
packaged and labeled with the study number, and will have a space where the subjects initial and
randomization number will be entered.
6.3 Drug Storage
Both drugs and placebo can be stored at room temperature in a locked storage area.
6.4 Accountability of drugs
Some drug records will be maintained centrally by the NIH PDS such as shipping
records. The individual sites will also maintain drug records locally such as drug dispensing and
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accountability records. Drugs will be dispensed to the sites by NIH PDS. Patients will be
required to pick up medications per visit schedule.
7.0 STATISTICAL CONSIDERATION
This is a double blind randomized crossover placebo controlled trial of statin use in HIV
positive patients with the specific aim of studying the effect of statins on HIV viral load. 22
chronically infected HIV positive patients will be randomized to either atorvastatin 80 mg
followed by placebo or placebo followed by atorvastatin (11 per sequence). After 8 weeks of
treatment and another 4 weeks washout period, patients in the placebo arm will receive
atorvastatin 80mg, whereas patients in the atorvastatin arm will be followed on placebo for
another 8 weeks. Table 2 displays the treatment sequence for the two groups.
Table 2
The effect of lipid lowering agents on HIV-1 RNA levels will be evaluated at the end of 7
weeks and at the end of 19 weeks. The primary goal of this study is to assess the treatment effect
by assuming that the carry-over effect is negligible. The primary strength of this cross-over trial
is increased efficiency because each patient serves as his or her own control, and the within-
subject variability is usually less than the between-subject variability. As a result, the sample size
for a cross-over trial will be lower than that for a comparable parallel group design. There is a
possible drawback of this design, however, if the carry-over effect cannot be ignored.
Based on historical data we estimate the standard deviation of the log10 viral load as.74
and the correlation coefficient of log10 viral loads before and after treatment as 0.83. To be
conservative, a correlation coefficient of 0.75 is used in our calculation. The paired t-test is used
(Week 0-7)
Week 8-11
(Week 12-19)
Atorvastatin 80mg
Washout
Placebo
Placebo
Washout
Atorvastatin 80mg
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for power calculation. A trial of 20 subjects has a power of 77% (with type I error 0.05) for
detecting a 1/3 log10 drop in viral load with atorvastatin. Power to detect a change of 0.4 or 0.5
in log10 viral load based on 10 patients per sequence is 90% and 98% respectively. Thus we
have excellent power to detect at least .4 log10 viral load difference by the treatment and
reasonable power to detect a 1/3 log10 viral load difference. Due to the possible loss to follow-
up (10%), 11 patients will be accrued in each sequence.
At the end of this study, the paired t-test will be used to test this hypothesis. If the
underlying distribution is clearly not close to a normal, then the sign-rank Wilcoxon test will be
used instead.
Secondary Objectives for Statistical Consideration
1- To study the difference in the expression of immune activation markers (i.e HLA DR
CD38 and Ki67 expression both percentage and number on CD4+ and CD8+ cells) between the
end of 7 weeks and the end of 19 weeks in the placebo and atorvastatin sequence. All
comparisons of changes between the end of 7 weeks and the end of 19 weeks, i.e. the difference
between months 19 and 7 or months 7 and 19 will be conducted by using the paired t-test if the
measurements are continuous. McNemar statistic will be used for the changes of discrete
markers.
Because of the randomization, the baseline measurements (at beginning of this trial) in
placebo and atorvastatin sequences should have the same distribution. This information can be
incorporated into an additional statistical analysis, called analysis of covariance ANCOVA. A
linear mixed effects model can be used to analyze the difference between the change of viral
loads evaluated at the beginning of this trial and at the end of the 7th week, and at the end of 11th
week and 19th week in atorvastatin and placebo sequence and placebo and atorvastatin sequence.
The difference of viral load at the end of 11th week in two treatment sequences can be used to
assess whether there is a treatment carryover effect.
Additional analyses will be conducted to assess whether there is any effect of drug on
change viral load, beyond that predicted by the change in LDL.
Finally the correlation between reductions in serum cholesterol and HIV viral load in
treatment arm will be assessed by using Spearman's correlation coefficient statistics.
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8.0 DATA COLLECTION AND MONITORING AND ADVERSE EXPERIENCE
REPORTING
8.1 Adverse and Serious Adverse Experience (SAE) reporting
8.1.1 Definition
An adverse event is defined as “undesired and unintended, though not unexpected, result
of therapy or intervention”.
An adverse event may also be defined as any “unfavorable and unintended sign
(including an abnormal laboratory finding), symptom, or disease temporally associated with the
use of an experimental medical treatment or procedure, regardless of whether it is considered
related to the medical treatment or procedure. These include both anticipated and unanticipated
risk”.A serious adverse event (SAE) is one “that results in death, is life threatening or results in
inpatient hospitalization or prolongs the existing hospitalization, results in a persistent or
significant disability of incapacity, or results in congenital anomaly / birth defect”. A serious
adverse event may not be immediately life threatening or result in death or hospitalization but
may jeopardize the patient/study participant or may require intervention to prevent one of the
other outcomes listed above.”
8.1.2 Reporting
All adverse events regardless of treatment group or relationship to the drug will need to
be reported to the necessary IRB as per their requirements. As reporting requirements are
somewhat different at NIAID and NNMC we will follow reporting requirements at both
institutions.
All SAE will be reported within 24 hours of when the investigator learns of this event. to
both the NIAID and the NNMC IRB. In addition to the above listed event any event that in the
investigators judgment is serious even if it does not meet the above criteria will be reported as
such.
Adverse events will be graded as per the attached toxicity table in Appendix 1. For toxicities
not listed in the table, grading will be based on the schema provided below
•
Grade 1: Transient or mild discomfort; no limitation in activity; no medical
intervention/therapy required.
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• Grade 2: Mild to moderate limitation in activity - some assistance may be needed; no or
minimal medical intervention/therapy required.
• Grade 3: Marked limitation in activity, some assistance usually required; medical
intervention/therapy required hospitalization possible.
• Grade 4: Extreme limitation in activity, significant assistance required; significant
medical intervention/therapy required hospitalization or hospice care.
Adverse events will also be assessed for their relation to study medications and
procedures.
Patients coming to the NIH clinical center often travel long distances and are hospitalized for
procedures that are routinely done as outpatients at other hospitals. Such elective hospitalizations
will not be reported as a SAE or an AE.
For all AEs, the clinician who examines and evaluates the subject will determine the
adverse event’s causality based upon the temporal relationship to administration of the study
agent, the pharmacology of the study agent, and his/her clinical judgment. Terms to describe the
degree of causality between the study agent and an event will be definitely, probably, possibly,
unlikely related or not related. The best estimate at the time of reporting of the causal
relationship between the experimental intervention and an adverse event and the degree of
certainty about causality will be graded as follows:
Definitely Related: The adverse event and administration of study agent are related in
time, and a direct association can be demonstrated (e.g., disappears or decreases with reduction
in dose or cessation of drug/investigational product and recurs with re-exposure).
Probably Related: The adverse event and administration of study agent are reasonably
related in time and/or follows a known pattern of response, and the adverse event is more likely
explained by study agent than other causes.
Possibly Related: The adverse event and administration of study agent are reasonably
related in time and/or follows a known pattern of response, and the adverse event can be
explained equally well by causes other than study agent (e.g., could readily have been produced
by the subject’s clinical state or could have been due to environmental or other interventions).
Unlikely Related: A potential relationship between study agent and the adverse event
could exist (i.e., the possibility cannot be excluded), but the adverse event is most likely
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explained by causes other than the study agent (e.g., could readily have been produced by the
subject’s clinical state or could have been due to environmental or other interventions).
Not Related: Adverse event is clearly due to extraneous causes (e.g., underlying disease,
environment) or exposure to the investigational product has not occurred. Such events MUST
have an alternative, definitive etiology documented in the patient’s medical record.
Therefore, a suspected adverse drug/investigational product reaction would be one that is
categorized as definitely, probably, possibly, and unlikely related to a study drug/ investigational
product”.
Please see attached appendix for the toxicity table. All adverse event reporting will end 4
weeks after the end of the study treatment.Any new toxicities not previously reported will be
submitted to Med-Watch.
As the study is being done at both the NIAID and at the NNMC reporting requirements
for both sites will be followed these include reporting all SAE within 24 hours after becoming
aware of a subject death or a potentially life threatening serious adverse event. This will meet the
reporting requirements of both the NIAID and the NNMC IRB, as the NIAID requires reporting
within 7 days and the NNMC requires reporting within 24 hours of knowledge of death or
potentially life threatening SAE. A completed NIAID IRB serious adverse event report will be
submitted to the NIAID IRB within 15 days after becoming aware of an inpatient hospitalization
(other than elective), a persistent or significant disability/incapacity, or a congenital
anomaly/birth defect. Investigators will report within 15 days any other event or condition
regardless of grade, which in their judgment represents an event reportable to the IRB. All other
serious adverse events will be reported to the NIAID IRB at the time of the annual review. In
addition a summary of all adverse events will be reported to the NIAID IRB with submission of
a request for continuing review.
8.2 Protocol monitoring and DSMB
Day to day protocol management will be provided by the PI at the NIH and by the
sponsors of the study at NNMC. As this is a randomized placebo controlled trial, a DSMB will
monitor the progress of the trial. The DSMB will be constituted through the NIAID. The DSMB
will evaluate data after enrollment and completion of study by 50% of the study patients.
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The trial will be conducted in compliance with this protocol, International Conference on
Harmonization Good Clinical Practices (ICH/GCP) and all applicable regulatory requirements.
Monitors under contract to the NIAID will visit the clinical research site(s) to monitor all aspects
of the study in accordance with the appropriate regulations. The objectives of a monitoring visit
will be: 1) to verify the prompt reporting of all data points, including reporting SAEs, checking
availability of signed informed consents; 2) to compare individual subject records and the source
documents (supporting data, laboratory specimen records and medical records to include
physician progress notes, nurse’ notes, subjects’ hospital charts); 3) to ensure protection of study
subjects, compliance with the protocol, and accuracy and completeness of records. The monitors
also will inspect the clinical site regulatory files to ensure that regulatory requirements are being
followed. During the monitoring visits, the investigator (and/or designee) and other study
personnel will be available to discuss the study progress and monitoring visit findings. The
investigator (and/or designee) will make study documents (e.g., consent forms) and pertinent
hospital, CRFs or clinical records readily available for inspection by the local IRB, the site
monitors, and the NIAID staff for confirmation of the study data
8.3 Data and Safety Monitoring Plan.
Day to day protocol management will be provided by the PI at the NIH and by the
sponsors of the study at NNMC. As this is a randomized placebo controlled trial, a DSMB will
monitor the progress of the trial. The DSMB will be constituted through NIAID. The DSMB will
evaluate data after 50% of the study patients have completed study.
8.4 Data management plan
“Study data will be collected and maintained on standardized Case Report Forms (CRF).
The study investigators will be responsible for assuring that the data collected is complete,
accurate, and recorded in a timely manner. Source documentation (the point of initial recording
of a piece of data) should support the data collected on the case report form, and be signed and
dated by the person recording and/or reviewing the data. Source documents include all
recordings of observations or notations of clinical activities and all reports and records necessary
for the evaluation and reconstruction of the clinical trial. Source documents include, but are not
limited to, the patient medical records, laboratory reports, ECG tracings, x-rays, radiologist
reports, patient diaries, biopsy reports, ultrasound photographs, patient progress notes, pharmacy
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records and any other similar reports or records of procedures performed during the subject’s
participation in the protocol. Data for CRFs will be collected during patient visits, phone calls
with subjects and health care providers, patient diaries and abstracted from the medical record. It
is not acceptable for the CRF to be the only record of the patient participation in the study. This
is to ensure that anyone who would access the patient medical record has adequate knowledge
that the patient is participating in a clinical trial.”
9.0 HUMAN SUBJECTS
Institutional Review Board (IRB) Review and Informed Consent
The protocol and any subsequent changes and the informed consent will be reviewed by
the IRB before initiation of the study. The informed consent will explain the study, the
procedures and the risks and benefits associated with the study. The study participants will be
provided copies of the informed consent for review, any questions that he/she may have about
the study will be answered prior to the final signing of the informed consent. A copy of the
consent form will be given to the subject and the informed consent process will be documented.
HIV infection in pediatric patients may represent a somewhat different disease; with
greater contributions from lymphoid organs such as thymus. We do not know whether children
and adults will represent a uniform group mechanistically, and we propose to study adults (≥
18y). As we obtain additional information, we may consider a pediatric study, although children
with HIV infection are no longer seen at NIH and such studies would be carried out in
collaboration.
9.1 Benefit
There is no immediate benefit to the patient. However, a potential benefit may be a
reduction in their viral load and temporary improvement in their lipid profile.
9.2 Risks
9.2.1 Medication associated risk
Atorvastatin
Per the package insert the following warnings are associated with atorvastatin use
Liver dysfunction-“persistent elevations (>3 times the upper limit of normal (ULN) occurring
on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received
Version 5.2
September 20, 2007
32
atorvastatin in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6% and
2.3% for 10, 20, 40 and 80 mg respectively.” Dose reduction, interruption or discontinuation of
atorvastatin resulted in reversal of these abnormalities.
Skeletal muscle- “rare cases of rhabdomyolysis with acute renal failure secondary to
myoglobinuria have been reported with atorvastatin use and with drugs in this class”
The following events have also been reported among patients in clinical trial of
atorvastatin at a frequency greater than 2% this include chest pain, nausea, bronchitis, rhinitis,
insomnia, dizziness, arthritis, urinary tract infection, peripheral edema. [42]
For events that were noted in less than 2% of the cases please refer to package insert appendix 2
9.2.2 Risks Associated with Hypocholesterolemia
Animal studies
As per the package insert a single female dog treated for 3 months with atorvastatin at a
dose of 120mg/kg/day, which would result in an exposure that is 16 times that seen in humans,
resulted in brain hemorrhage in the dog. Another female dog treated with escalating doses of
atorvastatin to a max of 280mg/kg/day suffered optic nerve vacuolation and brain hemorrhage.
In animal studies treatment with HMG CoA reductase inhibitors has resulted in
neurotoxicity. In normocholesterolemic dogs given doses of 180 mg/kg/day of lovastatin, this
dose is 180 times the normal therapeutic dose in humans, there was evidence of neurotoxicity in
37% of the animals. These dogs demonstrated a hemorrhagic encephalopathy. [43]
In a recent study designed to study the effects on coronary outcomes of lowering LDL
cholesterol to less than 100 mg/dl in patients with established coronary artery disease, 10,001
patients with established CAD were randomized to receive either atorvastatin 10 or 80 mg. The
median follow up in this study was 4.9 years. The mean LDL cholesterol achieved in the
atorvastatin 80 mg sub group was 77 mg/dl in this study. The authors of this study concluded that
there was no difference in reported adverse effects in those with LDL cholesterol less than 70
mg/dl.[39] The results of this study seemed to suggest that the reductions in LDL cholesterol
achieved in this population were well tolerated. However, not much is known about the effects of
temporary reductions in cholesterol and LDL in normo-cholesterolemic HIV positive patients.
Given the above animal data we will follow all patients on study and four weeks after
Version 5.2
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33
discontinuing placebo/statin for possible CNS and optic toxicities by targeted history and
physicals and laboratory testing as necessary.
There have been case reports of CNS side effects with statin use. These include reports of
memory loss, irritability and polyneuropathy. [44-46] These associations have however, not been
borne out in large clinical trials.
9.2.3 Risks Associated with Phlebotomy
Risks include bleeding, bruising, infection and syncope (fainting). Fainting and
complications thereof are rare but well recognized complications of phlebotomy. To minimize
risk, patients will undergo phlebotomy in the sitting position and will be monitored for 10
minutes after the procedure.
9.3. Confidentiality
All laboratory specimens, evaluation forms, reports, and other records that leave the site
will be identified by coded number only, to maintain subject confidentiality. The link to the
patient will be maintained at the site in a locked cabinet. All computer entry will be done with
coded numbers only. Clinical information will not be released without written permission of the
subject, except as necessary for monitoring by IRB, the FDA, the NIAID, the OHRP, the
pharmaceutical supporter(s), or the supporter’s designee. At the completion of the study the link
will be destroyed and the remaining samples will be stored without any link.
9.4 Study Discontinuation
The study may be discontinued at any time by the IRB, the NIAID, the FDA, or other
government agencies as part of their duties to ensure that research subjects are protected
9.5 Sample Storage
This section describes the storage and use of samples in this study.
Samples and data collected under this protocol may be used to study _HIV infection,
immune disorders and interactions of HIV and host immune metabolic and genetic factors.
Genetic testing will be performed. Access to research samples will be limited using a locked
room or a locked freezer or both. Samples and data will be stored using codes assigned by the
Version 5.2
September 20, 2007
34
investigators or their designees. Data will be kept in password-protected computers. Only
investigators or their designees will have access to the samples and data. Samples obtained at
NIH will be tracked in the Crimson system. Samples will be stored and tracked utilizing the NCI
FCRF REPOSITORY operated by SAIC FREDERICK. In the future, other investigators (both at
NIH and NNMC) may wish to study these samples and/or data. In that case, IRB approval must
be sought prior to any sharing of samples. Any clinical information shared about the sample
with or without patient identifiers would similarly require prior IRB approval. At the completion
of the protocol ( at termination), samples and data will either be destroyed, or after IRB approval,
transferred to another existing protocol or a repository.
The NIH Intramural Protocol Violation definition related to loss of or destruction of
samples (for example, due to freezer malfunction) will be followed in reporting to the IRB: The
violation compromises the scientific integrity of the data collected for the study.
Any loss or unanticipated destruction of samples (for example, due to freezer
malfunction) or data (for example, misplacing a printout of data with identifiers) that
compromises the scientific integrity of the study will be reported to the IRB.
Additionally, subjects may decide at any point not to have their samples stored. In this
case, the principal investigator will destroy all known remaining samples and report what was
done to both the subject and to the IRB. This decision may not affect the subject’s participation
in this protocol or any other protocols at NIH.
Version 5.2
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35
10.0 REFERENCES
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Palella FJ, Jr., Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al.
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Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000,356:1423-
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Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis,
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Ono A, Freed EO. Plasma membrane rafts play a critical role in HIV-1 assembly and
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Giguere JF, Tremblay MJ. Statin compounds reduce human immunodeficiency virus
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Iyengar S, Hildreth JE, Schwartz DH. Actin-dependent receptor colocalization
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Pontow SE, Heyden NV, Wei S, Ratner L. Actin cytoskeletal reorganizations and
coreceptor-mediated activation of rac during human immunodeficiency virus-
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8.
Popik W, Alce TM, Au WC. Human immunodeficiency virus type 1 uses lipid raft-
colocalized CD4 and chemokine receptors for productive entry into CD4(+) T cells.
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Moncunill G, Negredo E, Bosch L, Vilarrasa J, Witvrouw M, Llano A, et al. Evaluation
of the anti-HIV activity of statins. Aids 2005,19:1697-1700.
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Waters L, Stebbing J, Jones R, Mandalia S, Bower M, Stefanovic M, et al. The effect of
statins on HIV rebound and blips. J Acquir Immune Defic Syndr 2005,39:637-638.
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del Real G, Jimenez-Baranda S, Mira E, Lacalle RA, Lucas P, Gomez-Mouton C, et al.
Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med
2004,200:541-547.
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Sklar PA, Masur H, Grubb JR, Voell J, Witek J, Ono A, et al. Pravastatin does not have
a consistent antiviral effect in chronically HIV-infected individuals on antiretroviral
therapy. Aids 2005,19:1109-1111.
13.
Penzak SR, Chuck SK, Stajich GV. Safety and efficacy of HMG-CoA reductase
inhibitors for treatment of hyperlipidemia in patients with HIV infection.
Pharmacotherapy 2000,20:1066-1071.
14.
Peterlin BM, Trono D. Hide, shield and strike back: how HIV-infected cells avoid
immune eradication. Nat Rev Immunol 2003,3:97-107.
15.
Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs
2005,65:1747-1766.
16.
Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997,387:569-572.
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17.
Morita E, Sundquist WI. Retrovirus budding. Annu Rev Cell Dev Biol 2004,20:395-425.
18.
Gheysen D, Jacobs E, de Foresta F, Thiriart C, Francotte M, Thines D, De Wilde M.
Assembly and release of HIV-1 precursor Pr55gag virus-like particles from
recombinant baculovirus-infected insect cells. Cell 1989,59:103-112.
19.
Karacostas V, Nagashima K, Gonda MA, Moss B. Human immunodeficiency virus-
like particles produced by a vaccinia virus expression vector. Proc Natl Acad Sci U S
A 1989,86:8964-8967.
20.
Shioda T, Shibuta H. Production of human immunodeficiency virus (HIV)-like
particles from cells infected with recombinant vaccinia viruses carrying the gag
gene of HIV. Virology 1990,175:139-148.
21.
Freed EO. HIV-1 gag proteins: diverse functions in the virus life cycle. Virology
1998,251:1-15.
22.
VerPlank L, Bouamr F, LaGrassa TJ, Agresta B, Kikonyogo A, Leis J, Carter CA.
Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in
HIV type 1 Pr55(Gag). Proc Natl Acad Sci U S A 2001,98:7724-7729.
23.
Huang M, Orenstein JM, Martin MA, Freed EO. p6Gag is required for particle
production from full-length human immunodeficiency virus type 1 molecular clones
expressing protease. J Virol 1995,69:6810-6818.
24.
Demirov DG, Orenstein JM, Freed EO. The late domain of human immunodeficiency
virus type 1 p6 promotes virus release in a cell type-dependent manner. J Virol
2002,76:105-117.
25.
Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, Wang HE, et al.
Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.
Cell 2001,107:55-65.
26.
Demirov DG, Ono A, Orenstein JM, Freed EO. Overexpression of the N-terminal
domain of TSG101 inhibits HIV-1 budding by blocking late domain function. Proc
Natl Acad Sci U S A 2002,99:955-960.
27.
Bleiber G, May M, Martinez R, Meylan P, Ott J, Beckmann JS, Telenti A. Use of a
combined ex vivo/in vivo population approach for screening of human genes
involved in the human immunodeficiency virus type 1 life cycle for variants
influencing disease progression. J Virol 2005,79:12674-12680.
28.
Hall A. Rho GTPases and the actin cytoskeleton. Science 1998,279:509-514.
29.
Fenton RG, Kung HF, Longo DL, Smith MR. Regulation of intracellular actin
polymerization by prenylated cellular proteins. J Cell Biol 1992,117:347-356.
30.
Gougeon ML. Apoptosis as an HIV strategy to escape immune attack. Nat Rev
Immunol 2003,3:392-404.
31.
Janes PW, Ley SC, Magee AI. Aggregation of lipid rafts accompanies signaling via
the T cell antigen receptor. J Cell Biol 1999,147:447-461.
32.
Drake DR, 3rd, Braciale TJ. Cutting edge: lipid raft integrity affects the efficiency of
MHC class I tetramer binding and cell surface TCR arrangement on CD8+ T cells. J
Immunol 2001,166:7009-7013.
33.
Stanley SK, Ostrowski MA, Justement JS, Gantt K, Hedayati S, Mannix M, et al. Effect
of immunization with a common recall antigen on viral expression in patients
infected with human immunodeficiency virus type 1. N Engl J Med 1996,334:1222-
1230.
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34.
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in
the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised
placebo-controlled trial. Lancet 2004,364:685-696.
35.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al.
Prevention of coronary heart disease with pravastatin in men with
hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl
J Med 1995,333:1301-1307.
36.
Randomised trial of cholesterol lowering in 4444 patients with coronary heart
disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994,344:1383-
1389.
37.
Lennernas H. Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet
2003,42:1141-1160.
38.
Perger L, Kohler M, Fattinger K, Flury R, Meier PJ, Pauli-Magnus C. Fatal liver failure
with atorvastatin. J Hepatol 2003,39:1095-1097.
39.
Larosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive
Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl
J Med 2005.
40.
Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of
coronary and stroke events with atorvastatin in hypertensive patients who have
average or lower-than-average cholesterol concentrations, in the Anglo-
Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a
multicentre randomised controlled trial. Lancet 2003,361:1149-1158.
41.
Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular
drugs. Am J Cardiovasc Drugs 2004,4:281-297.
42.
Merck. Lipitor (Atorvastatin calcium). In.
43.
Berry PH, MacDonald JS, Alberts AW, Molon-Noblot S, Chen JS, Lo CY, et al. Brain
and optic system pathology in hypocholesterolemic dogs treated with a competitive
inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Am J Pathol
1988,132:427-443.
44.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory
loss: analysis of 60 case reports and review of the literature. Pharmacotherapy
2003,23:871-880.
45.
Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin
cholesterol-lowering drugs. Qjm 2004,97:229-235.
46.
Gaist D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH. Statins
and risk of polyneuropathy: a case-control study. Neurology 2002,58:1333-1337.
ICF_001.pdf:
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
• Adult Patient or • Parent, for Minor Patient
INSTITUTE:
National Institute of Allergy and Infectious Diseases
STUDY NUMBER:
06-I-0197
PRINCIPAL INVESTIGATOR: Frank Maldarelli, M.D.
STUDY TITLE:
A Randomized Placebo Controlled Trial of Atorvastatin in HIV Positive Patients Not on
Antiretroviral medications with the Specific Aims of Studying the Effects of Atorvastatin on HIV
Viral Load and Immune Activation Markers
Continuing Review Approved by the IRB on 4/14/08
Amendment Approved by the IRB on 03/20/08 (G)
Date Posted to Web: 05/06/08
Standard
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY
• Adult Patient or • Parent, for Minor Patient
NIH-2514-1 (4-97)
P.A.: 09-25-0099
File in Section 4: Protocol Consent (1)
INTRODUCTION
We invite you to take part in a research study at the National Institutes of Health (NIH).
First, we want you to know that:
Taking part in NIH research is entirely voluntary.
You may choose not to take part, or you may withdraw from the study at any time. In either case, you will not
lose any benefits to which you are otherwise entitled. However, to receive care at the NIH, you must be taking
part in a study or be under evaluation for study participation.
You may receive no benefit from taking part. The research may give us knowledge that may help people in the
future.
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research
treatments they would want to receive (such as blood transfusions). If you have such beliefs, please discuss them with
your NIH doctors or research team before you agree to the study.
Now we will describe this research study. Before you decide to take part, please take as much time as you need to ask
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other
health professional.
Purpose of the Study
HIV, the virus that causes AIDS, grows in the immune cells of the body. Recent research has shown that for the HIV to
multiply (replicate), it has to use some of the normal cell machinery. One of the pathways the virus uses to multiply
requires cholesterol (a kind of fat in the blood). Laboratory research has indicated that if the amount of cholesterol in
infected cells is reduced, HIV replication is also decreased. These experiments have been done only in the laboratory and
it is not known whether reducing cholesterol in people infected with HIV will also reduce HIV replication. In this study we
plan to investigate whether the use of cholesterol lowering drugs called statins will reduce HIV replication and lower the
level of HIV in the blood. We are studying the effects of one statin called atorvastatin (Lipitor), which has been approved
by the Food and Drug Administration (FDA) for treatment of persons with hyperlipidemia (elevated lipids in the blood).
Atorvastatin is not an approved treatment for HIV infection, and should not be considered a therapy for HIV; even if it
CONTINUATION SHEET for either:
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STUDY NUMBER:
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CONTINUATION: page 2 of 11 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
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does decrease HIV viral loads (the amount of the HIV virus in your blood), it is unlikely that atorvastatin alone will control
HIV. Atorvastatin is approved by the FDA for the treatment of hypercholesterolemia and is available for use outside this
study. However, atorvastatin is not FDA approved for treatment of HIV infection. As you are likely to have normal
cholesterol you may not receive any benefit from taking atorvastatin. The desire to take atorvastatin should not be a
reason for you to volunteer to take part in this study.
The primary purpose of this research study is to study the effect of this drug on HIV viral load. As part of this study we
will be looking at:
•
The amount of HIV virus in your blood (HIV viral load).
•
The composition of the strain of HIV virus that you carry (HIV genotype).
•
The response of your immune system to the virus.
•
Some of your genes that may determine the way this drug may or not work against your strain of the virus.
Study Procedures
You have already come to the clinic for a screening visit, and have undergone testing to determine whether or not you
qualify for the study. Based on your screening visit, you are eligible for the protocol and are invited to enroll in the study
phase. In the study phase, you will be randomly assigned (by chance, like the flip of a coin) to one of two study groups.
One study group will be asked to take atorvastatin, a medicine that reduces cholesterol and may affect the ability of your
virus to multiply. The other study group will take a placebo (something like a sugar pill) that should have no affect either
on the level of your cholesterol or the ability of your virus to multiply. Neither you nor your doctor will know whether you
will be in the drug or to the placebo pill group. Once you have been assigned to either the drug or the placebo pill
groups, you will remain in your groups/treatments for 8 weeks. Upon completion of 8 weeks, regardless of the study
group you were in, you will be required to discontinue all study related medications for 4 weeks. There may be some
circumstances where we may extend this off drug period to a total of 6 weeks. For instance, if you require the influenza
vaccination, which can sometimes affect HIV-1 viral RNA levels, we will administer the standard inactivated vaccine at the
beginning of the off drug period, followed by six week wash out. At the end of this period, you will be asked to switch
your study assignments i.e. if you were on the placebo pill you will switch to the study drug atorvastatin and vice versa if
you were on the study drug atorvastatin you will switch to the placebo pill. You will complete an additional 8 weeks on
this assigned study treatment; after this you will stop all study related treatment and be observed for an additional 4
weeks.
While on this research study you will have regularly scheduled study visits; at these visits you will have blood drawn,
symptoms assessed, physical examinations done, and a questionnaire given at regular intervals. You will be required to
come fasting for these visits as we will be drawing blood to check the fats (lipids) in your blood. This test can vary
depending on whether you are fasting or not. The blood will be used in standard as well as specialized tests. The
standard tests will include tests to determine the health of your liver, kidney, muscles, blood cells and your pregnancy
status as applicable. The specialized tests will include tests to determine the viral load (a measure of the amount of virus
in your blood), study the effects of the drug on your immune cells, the genotype (tests to study the composition of your
virus) and your own genes that might determine how the drug might, or might not work on you.
The table below details the number of visits, an estimate of the time you will be required to spend at each of the visits
and the procedures you will undergo during these visits. The volume of blood drawn at each visit will be no more than 75
cc (about 4 tablespoons). This table is merely an approximation of what you can expect as a subject in this study, you
may be required to undergo additional testing based on signs and symptoms that you may develop while on the study.
CONTINUATION SHEET for either:
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STUDY NUMBER:
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CONTINUATION: page 3 of 11 pages
PATIENT IDENTIFICATION
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P.A.: 09-25-0099
Week
0 to 4
0
1
2
6
1
2
1
3
1
4
1
8
2
0
2
4
Visit
1
2
4
5
6
7
9
1
0
1
1
1
2
1
3
1
4
Phase
Screening
Study
Approximate time
(hrs)
2.
5
3
0
m
i
n
3
0
m
i
n
2
4
5
m
i
n
4
5
m
i
n
4
5
m
i
n
2
4
5
m
i
n
4
5
m
i
n
4
5
m
i
n
2
1
.
5
Procedure
Consent process
X
Clinical assessment
X
X
X
X
X
X
X
X
X
X
X
Questionnaire (fatigue
scale)
X
X
X
Physical exam
X
X
X
X
X
Blood draws
X
X
X
X
X
X
X
X
X
X
X
X
X
Atorvastatin or
placebo
X
X
X
X
X
X
X
X
X
X
CONTINUATION SHEET for either:
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STUDY NUMBER:
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CONTINUATION: page 4 of 11 pages
PATIENT IDENTIFICATION
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Study Population
We plan to enroll 22 subjects for this study and the anticipated duration on study for each subject is 30 weeks.
Summary of Entry Criteria
To participate in the study you must:
•
Be greater than 18 years of age
•
Be infected with the HIV-1 virus
•
Off all Antiretroviral therapy (ART) “medicines taken to control the virus multiplication” for greater than three
months prior to study entry. While of ART you must have a stable viral load “amount of virus in your blood”.
•
Be willing to use a method of contraception during the study period. Adequate methods of birth control include:
condoms, male or female, with or without a spermicide; diaphragm or cervical cap with spermicide; intrauterine
device; any of the methods that require a prescription (such as contraceptive pills or patch, Norplant, Depo-
Provera, and others) or a male partner who has previously undergone a vasectomy,
•
Be willing to have blood drawn
•
Have no known allergy or contraindication to atorvastatin use
•
Have the ability to understand and willingness to sign the informed consent
•
Be willing to have blood stored for future testing including tests that will study your genes and the genetics of the
virus
•
Have a CD4 cell count “a measure of your immune cells” greater than 350 cells/ml
•
Have three viral loads that average greater than 1000 copies/ml within a 4 week period.
•
Have a near normal total cholesterol “a kind of fat in the body” lower than 240mg/dl and a LDL cholesterol “a kind
of fat in the body” lower than 130mg/dl
•
Have near normal results for tests that test the health of your kidney, pancreas, liver, blood and muscles.
•
Have a negative serum pregnancy test and not be breast feeding prior to taking the study drugs
To Participate in the Study You Must Not
•
Be actively using recreational drugs or alcohol, as this might affect your ability to participate in the study
•
Have had a serious illness or opportunistic infections “illnesses that occur in people with a weakened immunity”
that required hospitalization in the 30 days prior to study entry
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CONTINUATION: page 5 of 11 pages
PATIENT IDENTIFICATION
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P.A.: 09-25-0099
•
Have evidence of any cancer or opportunistic illness that will require treatment during the study period except
some kinds of skin cancer
•
Allergy to the study medication “atorvastatin” or any of its components
•
Have had a history of myositis or rhabdomyolysis (diseases that result in muscle injury or swelling “inflammation”)
with use of any statins
•
Have had a history of diseases of the muscle such as poly or dermatomyositis (these are diseases of the muscle
which result in swelling or “ inflammation” of the muscle)
•
Be on any medication that do not mix “interact” with the study drug “ atorvostatin” . Please see the attached
listing If you are any of these medications please let your physician know.
•
Use St.Johns wort as this can increase the amount of the study drug in your body
•
Use grape fruit or grape fruit juice, as this can increase the levels of study drug in your body
•
Be on any medication that might affect your immune response
•
Have a low LDL cholesterol ( a kind of fat in your body ) that is less than 40 mg/dl
•
Have had any vaccines within 6 weeks of entry into the study
Withdrawal From the Protocol
You may choose to withdraw from the protocol at any time. We may choose to withdraw you from the protocol at any
time if we think it is not in your best interest to continue on the protocol, or if you fail to comply with the requirements
of the protocol or if the DSMB, a panel of independent investigators who will review the data after we accrue 50 % of
the patients, decides to stop the protocol. If the protocol is terminated for unanticipated reasons you will be withdrawn
from the study. If you need to start antiretroviral therapy, you will be withdrawn from the study and referred to your
primary physician. Any decision to start antiretroviral therapy will be done in consultation with your primary physician. If
you need to start antiretroviral therapy you should do so after you have discontinued atorvastatin for one week. You
may also be withdrawn from the study if blood tests that measure your liver functions are greater than 3 times the
upper limit of normal on two successive measurements.
Duration of Study
The study will take 24 weeks to complete once you have been assigned to your group.
Risks/Discomforts/Monitoring
Risks
The possible risks and discomforts from being in this research study include risks from the study medication, from
reductions in your cholesterol, those associated with phlebotomy (blood draw). Each one of these risks is explained in
detail below:
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 6 of 11 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
Atorvastatin - The use of this drug in research studies (clinical trials) designed to win approval of this drug have
demonstrated that about 2% of the population reported different side-effects such as chest pain, nausea, bronchitis
(inflammation of the bronchus), rhinitis (similar to a runny nose), arthritis (swelling and inflammation of the joints),
insomnia (difficulty sleeping) and dizziness, urinary tract infection and peripheral edema (swelling of your feet/leg). In
addition this drug has been associated with increases in liver enzymes and rarely fatal liver failure. However, in most
cases the liver enzymes come back to where they started (baseline) if the drug is stopped. This drug has also been
associated with increases in muscle enzymes, muscle pain and a complication called rhabdomyolysis. This complication
refers to a condition that is associated with injury to your muscles that can sometimes lead to kidney failure. There have
also been some cases of altered behavior, memory loss and inflammation of the nerves (peripheral neuropathy) with the
use of this drug.
While all risks to you cannot be foreseen, all attempts will be made to ensure your safety. This will include testing your
blood, reviewing your symptoms and doing physical examinations at regular intervals as previously described. In addition
a data safety monitoring board, which consists of a panel of individuals not associated with the study, will evaluate the
data collected after half the subjects have been enrolled and completed the study. If this board feels that this trial should
be discontinued because it poses a risk to the participants, the trial will be discontinued.
Pregnancy - Atorvastatin belongs to a class of drugs referred to as statins. This group of drugs cannot be used during
pregnancy as it may cause damage to the unborn baby. To participate in this study you will be required to use two
reliable methods of contraception at all times while you are on this study and will undergo periodic testing to confirm your
pregnancy status. If you become pregnant while on study you will be asked to discontinue all on study medications. We
will continue to follow you throughout the pregnancy and immediately after pregnancy to assess for adverse effects.
Hypocholesterolemia (low cholesterol) - As your cholesterol (a kind of lipid in your blood) will be normal at the
beginning of the study we anticipate that your cholesterol will fall during this study because the drug being used is known
to reduce cholesterol. Not much is known about what happens in humans when the cholesterol falls to a very low level.
In animal studies when the cholesterol levels fall to very low levels, there are reports of damage to the brain and eyes.
We will ensure that your cholesterol does not fall to such levels, by ensuring that a physician not associated with the
study team, reviews your cholesterol. If he/she feels that your cholesterol is too low (that is levels that could be
potentially harmful) he will discuss this with the study investigators and you will be withdrawn from the study. In addition
all subjects will be followed for signs and symptoms and problems with your nervous system/ eyes.
Phlebotomy (sampling of blood by needle puncture) - The risks associated include bleeding, bruising, and fainting.
To minimize risk, patients will have their blood taken in the sitting position and will be monitored for 10 minutes after the
procedure.
Benefits
You will not benefit from taking part in this study, but the information we learn may help us with the management of HIV
positive patients in the future. This includes the availability of a drug that is frequently used in the management of some
of the complications of drugs currently used to control the virus and may have the potential to control the quantity of
virus and affect the immune response in HIV positive patients.
Compensation
To compensate for your time and inconvenience of this protocol, you will be paid a total of $600.00 at the end of the
study. If you choose to leave the study before the end, you will be paid according to the amount of time you participated,
$50 for each visit you complete. The compensation will be provided as a lump sum at the end of your participation. If
you need to stop the study because of toxicity, you will be paid the total amount.
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 7 of 11 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
Alternatives to Participation
This study provides no direct benefits to participants. You are in no way obligated to continue in the protocol even if you
are eligible. The alternative to participation is not to enroll.
Additional Information
There will be no cost to you for study medications, clinic visits, examinations or laboratory and test procedures that are
part of this study and that are obtained at the NIH. Medical costs of other treatment outside this study and outside of
the NIH will not be the responsibility of the NIH. The NIH will provide only study-related medical care, and medical care
and medications not directly related to the study must continue to be provided by your personal physician. We will be
sending letters regarding your study participation and your care to your doctor routinely and as needed, and we will
also use the fax and the phone to relay information to your doctor that he or she should know to best care for you. We
will not ask your permission for each of these contacts. We will contact the physician you have named as your doctor,
but you may give us a different physician to contact instead at any time. Once your participation in this study is
completed, you will not be eligible for continuing care at NIH, unless you are eligible for another study at the NIH, but
your doctors at NIH will be glad to provide telephone consultation to your own doctor on request. During the study,
you will be told about any research that relates to your study, especially any findings from the study itself.
Genetic Testing
Some of the blood drawn from you as part of this study will be used for genetic tests. Genetic tests can help researchers
study how health or illness is passed on to you by your parents or from you to your children. Some things to consider in
thinking about whether or not to participate in these genetic studies include the possible effects on your emotional well
being. In other words, how might you feel about yourself and your life if you learn information about risks that could
affect your own health or that of your children? There may be no treatment for certain conditions and this may cause
some individuals to feel anxious, depressed, or stressed. Additional genetics counseling and advice is available from the
National Institutes of Health to help you understand the nature and implications of findings about you and your family.
Also, relationships with other family members may be affected by finding out risks they have but did not want to know.
An example would be if your children, brothers or sisters find out they have risks for health problems because of
information found out about you.
Some of the blood drawn from you as part of this study may be used for a test for HLA type, which is a genetic test of
markers of the immune system. It is usually used to match bone marrow or organ transplants. For research, HLA testing
might be used to try to identify factors associated with the progression of HIV disease or related conditions. In addition,
determining HLA type is necessary to be able to perform certain research studies. Some HLA types have been associated
with an increased risk of certain diseases like arthritis and other rheumatologic problems. However, simply having those
HLA types doesn’t mean you will develop these diseases.
Genetic testing can also be used to determine if people are directly related. These tests can reveal that a person’s
biological parents are someone other than their legal parents. If these facts were not known previously they could be
troubling to learn. It is our policy to not discuss such information unless it has direct medical or reproductive implications
for you or your family. By agreeing to participate in this study, you do not waive any rights that you may have regarding
access to and disclosure of your records. For further information on those rights, please contact Dr. Maldarelli, principal
investigator. Any genetic information collected or discovered about you or your family will be confidential. Medical
records containing this information will be kept under lock and key. We will not release any information about you or your
family to relatives, any insurance company, or employer unless you sign a release requesting us to do so. Genetic
information can be requested and obtained when a person applies for health insurance or a job and has signed a release.
CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
06-I-0197
CONTINUATION: page 8 of 11 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
Stored Samples and Future Research
Blood left over from this study will be stored. These stored samples will help us learn more about HIV, immune deficiency
or related conditions. In general, the research tests we perform are not like routine medical tests, and may not relate
directly to your medical care, so we may not put future test results in your medical record. However, if you wish,
someone on the study team will discuss the test results with you. We will not share these test results with your private
doctor unless you ask us to do so.
By agreeing to participate in this study, you do not waive any rights that you have regarding access to and disclosure of
your records. For further information on those rights, please contact Dr. Maldarelli.
Labeling of Stored Samples
We will label your stored samples with a code that only the study team can link to you. We will keep any information that
can be traced back to you private to the extent permitted by law.
Future Studies
Other investigators may want to study your stored samples. If so, the NIH study team may send your samples to them,
along with a coded label. The study team may also share information such as your gender, age, health history, or
ethnicity. In some cases, an Institutional Review Board (IRB) will review new research proposals that would like to use
your samples. The IRB is a committee that oversees medical research studies to protect volunteers’ rights and welfare.
Investigators will only use your samples for research. We will not sell them. Future research that uses your samples may
lead to new products, but you will not receive payment for these products. Some future studies may need health
information (such as smoking history or present health status) that we don’t already have. If so, the NIH study team will
contact you for this information.
Benefits
In general, future research that uses your samples will not help you, but it may help us learn what causes AIDS, immune
deficiency, or related conditions. This research may also help us learn how to prevent or treat the condition.
Risks
The greatest risk is that someone may take information from your medical records without your permission. The chances
of this happening are very low. If this information becomes available, you may face discrimination when you apply for
insurance or a job. You may also have similar problems if you share the information yourself or let us release your
medical records.
Making Your Choice
If you agree to participate in this study, you agree to let us store your samples for future research. You also agree that
we can contact you again in the future. No matter what you decide, you may still participate in other studies at NIH.
However, your refusal to let us store your samples may lead to your withdrawal from this specific study. Even if you agree
now to let us store your samples, you can change your mind later. If you do, please contact us and say that you do not
want us to use your samples for future research.
MEDICAL RECORD
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
CONTINUATION: page 9 of 11 pages
PATIENT IDENTIFICATION
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
NIH-2514-3 (5-02)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
As part of your participation in this study, it will be necessary to test your blood for the presence of antibodies to the
Human Immunodeficiency Virus (HIV), the virus that causes Acquired Immune Deficiency Syndrome (AIDS). In order to
perform the test, a small amount of blood (approximately 2 teaspoons) will be withdrawn from one of your arms with a
needle. You may experience some slight discomfort at the needle entry site and there may be some bruising. In
addition, there is a very small risk of you fainting or of infection at the needle entry site. If your test results are found
to be positive, or if you are otherwise diagnosed as having AIDS, you should be aware of the following Clinical Center
HIV Testing Policy:
1.
Your physician will notify you promptly of the HIV test results.
2.
Your physician and/or the Clinical Center HIV counselor will offer you, and any current and/or ongoing
sexual partner(s) (spouses are generally considered to be current or ongoing sexual partners) or needle-sharing
partner(s) you identify, information on the meaning of the test results and how to prevent the spread of the
infection.
3.
Because the virus may be transmitted in several ways, it is important that you inform sexual and/or
needle-sharing partner(s) that any, or all, of them may have been exposed to the HIV virus and encourage
them to be tested. If you request it, staff at the Clinical Center will assist you in notifying your partner(s) and
arrange counseling for them through an HIV counselor.
4.
The results of your HIV test and/or documentation of the diagnosis of AIDS will become a part of your
Clinical Center medical record and, as such, will be protected from unauthorized disclosure by the Federal
Privacy Act of 1974. In general, access to your medical record will be restricted to those health care
professionals directly involved in your care or in the conduct of ongoing biomedical research, and information is
not usually released to other third parties without your permission or that of your designated representative.
However, there are some particular routine uses of such information of which you should be aware.
a. If you are unwilling or unable to notify your partner(s), the Clinical Center is responsible for
attempting to contact and inform them of their possible exposure to the virus. Reasonable attempts
will be made to protect your identity including withholding your name when notifying any partner(s) of
their possible exposure. Some notification or counseling of current and/or ongoing partners may be
carried out through arrangements with, or referral to, local public health agencies.
b. A summary of your care at the Clinical Center will be sent to the physician who referred you here for
treatment.
c. The Clinical Center may report certain communicable diseases, such as HIV infection, to appropriate
State and Federal government agencies.
i.
For Clinical Center patients who are Maryland residents, the Clinical Center reports by “Patient
Unique Identifier Number” (rather than by name) newly obtained HIV-positive results from its
laboratory to the Maryland Department of Health and Mental Hygiene. Patient Unique Identifier
Number is: last four digits of social security number, birth month, birth day, birth year, race and
gender.
MEDICAL RECORD
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
CONTINUATION: page 10 of 11 pages
PATIENT IDENTIFICATION
INCLUSION OF HIV TESTING IN CONSENT TO
PARTICIPATE IN A CLINICAL RESEARCH STUDY
NIH-2514-3 (5-02)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
ii.
For Clinical Center patients who are Maryland residents, the Clinical Center reports by name new
cases of AIDS to the Maryland Department of Health and Mental Hygiene.
iii.
For Clinical Center patients who are not Maryland residents, the Clinical Center
reports HIV-positive results and/or AIDS to the patient’s primary care/referring physician.
If you have any questions regarding the HIV testing or the information provided above, you are encouraged to discuss
them with your physician and/or a Clinical Center HIV counselor: (301) 496-2381.
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
• Adult Patient or • Parent, for Minor Patient
STUDY NUMBER:
06-I-0197
CONTINUATION: page 11 of 11 pages
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY (Continuation Sheet)
• Adult Patient or • Parent, for Minor Patient
NIH-2514-1 (5-98)
P.A.: 09-25-0099
FAX TO: (301) 480-3126
File in Section 4: Protocol Consent
OTHER PERTINENT INFORMATION
1. Confidentiality. When results of an NIH research study are reported in medical journals or at scientific meetings,
the people who take part are not named and identified. In most cases, the NIH will not release any information about
your research involvement without your written permission. However, if you sign a release of information form, for
example, for an insurance company, the NIH will give the insurance company information from your medical record.
This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you
insurance.
The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the
Act allows release of some information from your medical record without your permission, for example, if it is required
by the Food and Drug Administration (FDA), members of Congress, law enforcement officials, or other authorized
people.
2. Policy Regarding Research-Related Injuries. The Clinical Center will provide short-term medical care for any
injury resulting from your participation in research here. In general, no long-term medical care or financial
compensation for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or
the Federal Government. However, you have the right to pursue legal remedy if you believe that your injury justifies
such action.
3. Payments. The amount of payment to research volunteers is guided by the National Institutes of Health policies.
In general, patients are not paid for taking part in research studies at the National Institutes of Health.
4. Problems or Questions. If you have any problems or questions about this study, or about your rights as a
research participant, or about any research-related injury, contact the Principal Investigator, Frank Maldarelli, M.D.,
Building: 10, Room 12S245, Telephone: (301) 435-8019. Other investigators you may call are Rose McConnell (301)
443-5643.
You may also call the Clinical Center Patient Representative at 301-496-2626.
5. Consent Document. Please keep a copy of this document in case you want to read it again.
COMPLETE APPROPRIATE ITEM(S) BELOW:
A. Adult Patient’s Consent
B. Parent’s Permission for Minor Patient.
I have read the explanation about this study and have been given the
opportunity to discuss it and to ask questions. I hereby consent to take
part in this study.
I have read the explanation about this study and have been given the
opportunity to discuss it and to ask questions. I hereby give permission
for my child to take part in this study.
(Attach NIH 2514-2, Minor’s Assent, if applicable.)
Signature of Adult Patient/Legal Representative
Date
Signature of Parent(s)/Guardian
Date
C. Child’s Verbal Assent (If Applicable)
The information in the above consent was described to my child and my child agrees to participate in the study.
Signature of Parent(s)/Guardian
Date
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE
FROM APRIL 14, 2008 THROUGH APRIL 13, 2009.
Signature of Investigator
Date
Signature of Witness
Date
| 2
|
arm 1: Patients were randomized to receive Atorvastatin first for 8 weeks, followed by 4 weeks wash out, and then cross over to placebo for 8 weeks. arm 2: Patients were randomized to receive placebo first for 8 weeks, followed by 4 weeks wash out, and then cross over to 80 mg atorvastatin daily for 8 weeks.
|
[
0,
0
] | 2
|
[
0,
0
] |
intervention 1: 80 mg atorvastatin oral daily intervention 2: patients will be administered placebo
|
intervention 1: Atorvastatin intervention 2: Placebo
| 3
|
San Diego | California | United States | -117.16472 | 32.71571
Bethesda | Maryland | United States | -77.10026 | 38.98067
Bethesda | Maryland | United States | -77.10026 | 38.98067
| 0
|
NCT00367458
|
[
4
] | 335
|
RANDOMIZED
|
SINGLE_GROUP
| 9OTHER
| 1SINGLE
| true
| 0ALL
| false
|
Compare 2 application techniques of ChloraPrep Swabstick--3 swabsticks at once versus 3 swabsticks used sequentially. Hibiclens applied according to the manufacturer's directions. Sterile swabsticks (wetted with sterile deionizd water) applied using the same method as the ChloraPrep Swabstick.
|
Determine differences (if any) in 2 different application techniques of ChloraPrep Swabstick--3 swabsticks at once versus 3 swabsticks used sequentially. Hibiclens, a liquid antibacterial soap, applied according to the manufacturer's directions as a active/positive comparison. Sterile swabsticks (wetted with sterile deionized water) applied as a negative comparison using the same method as the ChloraPrep swabstick.
Study uses topical sampling from the abdomen and the groin on intact skin and evaluates the germs left on the skin after treatment with ChloraPrep Swabsticks.
|
Topical Antisepsis
|
antimicrobial antisepsis
|
Prot_SAP_000.pdf:
| 5
|
arm 1: Chlorhexidine gluconate (CHG) 2% w/v CHG/isopropyl alcohol (IPA) 70% v/v - 3 swabsticks applied @ same time arm 2: Chlorhexidine gluconate (CHG) 2% w/v and isopropyl alcohol (IPA) 70% v/v - 3 swabsticks applied sequentially arm 3: Chlorhexidine gluconate (CHG) 4% w/v in an aqueous base arm 4: Sterile swabstick wetted with sterile deionized water - 3 swabsticks applied at the same time. arm 5: Sterile swabstick wetted with sterile water--3 swabsticks applied sequentially.
|
[
0,
0,
1,
2,
2
] | 5
|
[
0,
0,
0,
10,
10
] |
intervention 1: 3 swabsticks topically applied at the same time to intact skin intervention 2: Chlorhexidine gluconate 2% w/v and isopropyl alcohol 70% v/v; 3 swabsticks applied sequentially to intact skin. intervention 3: Chlorhexidine gluconate 4% w/v in an aqueous base applied according to mfr's directions. Step 1) 5 ml of Hibiclens applied to a sterile gauze pad. Step 2) Product applied to treatment area on intact skin for 2 minutes. Area dried with sterile towel or sterile gauze. Steps 1 and 2 repeated. intervention 4: 3 sterile swabsticks wetted with sterile water topically applied to intact skin at the same time. intervention 5: Sterile swabsticks wetted with sterile water topically applied to intact skin one-at-a-time.
|
intervention 1: CHG 2% w/v & IPA 70% v/v, swabstick (3 @ once). intervention 2: CHG 2% w/v & IPA 70% v/v swab applied sequentially intervention 3: Aqueous CHG 4% w/v applied according to mfr's directions intervention 4: Sterile swabstick with sterile water (3 @ once) intervention 5: Sterile swabstick with sterile water (one-at-a-time)
| 1
|
Sterling | Virginia | United States | -77.4286 | 39.00622
| 0
|
NCT00799812
|
[
3
] | 4
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
hOKT3gamma1 (Ala-Ala) is a man-made antibody that is commonly used to prevent organ rejection. The purpose of this study is to determine whether hOKT3gamma1 (Ala-Ala) is safe and effective in psoriatic arthritis patients who are unable to control their arthritis with methotrexate or azathioprine.
|
Psoriatic arthritis is a form of inflammatory arthritis that affects approximately 7% of people who have psoriasis. Treatment typically include drugs such as methotrexate, azathioprine, and etanercept, which suppress the immune system in a nonspecific fashion in an attempt to control the immune responses causing the disease. In some severe cases of psoriatic arthritis, these drugs cannot adequately control the disease, often requiring patients to undergo continuous treatment to prevent or combat disease activity. hOKT3gamma1 (Ala-Ala) is a genetically engineered monoclonal antibody directed against the CD3 antigen on T cells. hOKT3gamma1 (Ala-Ala) specifically targets immune cells that are actively involved in destructive immune responses, such as those that cause psoriatic arthritis. In a small pilot study of eight people with psoriatic arthritis who received a 2-week course of hOKT3gamma1 (Ala-Ala), the drug appeared safe and caused no serious side effects. This study will test the safety and efficacy of hOKT3gamma1 (Ala-Ala) in alleviating symptoms in psoriatic arthritis patients.
This study will last 2 years. Individuals with psoriatic arthritis who are receiving methotrexate or azathioprine therapy and have active disease are eligible to participate. Participants will be randomly assigned to receive hOKT3gamma1 (Ala-Ala) or placebo. Participants will receive a 5-day treatment with the drug or placebo every month for the first 4 months of the study. There will be 5 study visits over 2 years to assess the safety and effectiveness of hOKT3gamma1 (Ala-Ala) and to evaluate laboratory measures related to the underlying immune problems that cause psoriatic arthritis.
|
Arthritis, Psoriatic
|
Psoriatic Arthritis Arthritis Psoriasis Psoriatic PsA
| null | 2
|
arm 1: Escalating dose of hOKT3gamma1 (Ala-Ala) given intravenously over 5 days of each 28 day cycle arm 2: Intravenous dose of placebo given over 5 days of each 28 day cycle
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Escalating dose given IV over 5 days (1mg, 2mg, 4mg on days 3-5) of each 28 day cycle intervention 2: Intravenous dose of placebo given over 5 days of each 28 day cycle
|
intervention 1: hOKT3gamma1(Ala-Ala) intervention 2: Placebo
| 2
|
Aurora | Colorado | United States | -104.83192 | 39.72943
Chicago | Illinois | United States | -87.65005 | 41.85003
| 0
|
NCT00239720
|
[
3
] | 133
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This is a double-blind, placebo-controlled, randomised crossover study to investigate the efficacy and safety of GW876008
| null |
Irritable Bowel Syndrome (IBS)
|
Irritable Bowel Syndrome safety
| null | 2
|
arm 1: GW876008 arm 2: Placebo
|
[
0,
2
] | 2
|
[
0,
10
] |
intervention 1: None intervention 2: None
|
intervention 1: GW876008 intervention 2: Placebo
| 23
|
Sherwood | Arkansas | United States | -92.22432 | 34.81509
Concord | California | United States | -122.03107 | 37.97798
Los Angeles | California | United States | -118.24368 | 34.05223
Tampa | Florida | United States | -82.45843 | 27.94752
Stockbridge | Georgia | United States | -84.23381 | 33.54428
Louisville | Kentucky | United States | -85.75941 | 38.25424
Monroe | Louisiana | United States | -92.1193 | 32.50931
Boston | Massachusetts | United States | -71.05977 | 42.35843
St Louis | Missouri | United States | -90.19789 | 38.62727
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Anderson | South Carolina | United States | -82.65013 | 34.50344
Greer | South Carolina | United States | -82.22706 | 34.93873
Chattanooga | Tennessee | United States | -85.30968 | 35.04563
Germantown | Tennessee | United States | -89.81009 | 35.08676
Austin | Texas | United States | -97.74306 | 30.26715
San Antonio | Texas | United States | -98.49363 | 29.42412
Lynchburg | Virginia | United States | -79.14225 | 37.41375
Truro | Nova Scotia | Canada | -63.26538 | 45.36685
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
| 0
|
NCT00421707
|
[
3
] | 21
|
NA
|
SINGLE_GROUP
| 1PREVENTION
| 0NONE
| false
| 0ALL
| null |
This phase II trial studies how well pioglitazone hydrochloride works in preventing head and neck cancer in patients who have oral leukoplakia. Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of pioglitazone hydrochloride may be effective in preventing head and neck cancer.
|
PRIMARY OBJECTIVES:
I. Determine whether pioglitazone (pioglitazone hydrochloride) reverses leukoplakia in patients with hyperplastic or dysplastic oral cavity or oropharyngeal leukoplakia.
SECONDARY OBJECTIVES:
I. Determine the safety and tolerability of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.
Patients are followed up at 4, 8, 12, and 16 weeks.
|
Head and Neck Cancer Oral Leukoplakia
| null | 1
|
arm 1: Patients receive pioglitazone hydrochloride PO QD for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.
|
[
0
] | 1
|
[
0
] |
intervention 1: Given PO
|
intervention 1: pioglitazone hydrochloride
| 1
|
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
| 0
|
NCT00099021
|
|
[
4
] | 68
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
After 24 weeks of treatment, to assess the A1C-lowering efficacy of sitagliptin 100 mg once daily added to the regimen of patients with inadequate glycemic control on metformin monotherapy
| null |
Diabetes Mellitus, Non-Insulin-Dependent
| null | 3
|
arm 1: sitagliptin + metformin arm 2: metformin + any other oral antidiabetic drug arm 3: metformin
|
[
0,
1,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: sitagliptin 100 mg Once a day (QD) for 24 weeks intervention 2: metformin 850 mg Twice a day (BID) for 24 weeks intervention 3: metformin 500 mg Three times a day (TID) to 850 mg Twice a day (BID), for 24 weeks intervention 4: Patient can take any oral antidiabetic drug (other than metformin)
|
intervention 1: sitagliptin phosphate intervention 2: Comparator: metformin intervention 3: Comparator: metformin intervention 4: Comparator: Antidiabetic Standard of Care
| 0
| null | 0
|
NCT00875394
|
|
[
3
] | 23
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
Open label, uncontrolled Phase II trial to assess the efficacy and safety of BI 2536 in second line treatment in sensitive-relapse SCLC patients.
| null |
Carcinoma, Small Cell
| null | 1
|
arm 1: Total Patients
|
[
0
] | 1
|
[
0
] |
intervention 1: Intravenous Infusion
|
intervention 1: BI 2536
| 10
|
Fayetteville | Arkansas | United States | -94.15743 | 36.06258
Chicago | Illinois | United States | -87.65005 | 41.85003
Evanston | Illinois | United States | -87.69006 | 42.04114
Boston | Massachusetts | United States | -71.05977 | 42.35843
St Louis | Missouri | United States | -90.19789 | 38.62727
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greenville | South Carolina | United States | -82.39401 | 34.85262
Seattle | Washington | United States | -122.33207 | 47.60621
Edmonton | Alberta | Canada | -113.46871 | 53.55014
| 1
|
NCT00412880
|
|
[
0
] | 96
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| true
|
Past research has demonstrated that cocaine dependent women experience less severe responses to cocaine during the luteal phase of the menstrual cycle, when estrogen and progesterone concentrations are high. The purpose of this study is to determine whether administered progesterone reduces subjective and physiological responses to cocaine in cocaine dependent individuals.
|
Changes in ovarian hormones across the menstrual cycle impact responses to cocaine in women. Studies have shown that cocaine's effects are dampened during the luteal phase of the menstrual cycle, when estrogen and progesterone concentrations are high, relative to the other phases of the cycle, when concentrations of these hormones are relatively low. The purpose of this study is to determine whether progesterone reduces subjective and physiological responses to cocaine in cocaine dependent individuals. In addition, this study will help to advance the possibility of hormonal progesterone and pharmacologically-related drugs as potential treatment components for cocaine abuse.
Participants will undergo two 4-day inpatient periods, totaling 8 days of treatment. For women, the inpatient periods will occur during two consecutive menstrual cycles; for men, these will occur during two consecutive months. On Day 1, participants will receive a first dose of either progesterone or placebo. On Day 2, participants will receive a second and third dose of study medication. Participants will also participate in an adaptation session, which will familiarize the participant with the smoking equipment that will be used the following day. On Day 3, participants will receive a fourth dose of medication 2 hours prior to a smoking lab session. Prior to beginning the smoking lab session, participants will be asked to rate their current cocaine craving, anxiety level, appetite, and premenstrual symptoms. Participants will then be given a sample of the cocaine dose for the given day. During the smoking lab session, participants will be asked additional cocaine craving questions at pre-determined intervals and will be given the option to trade in previously earned tokens for either money or a dose of cocaine. Following completion of the smoking lab session, participants will receive their fifth dose of medication.
|
Cocaine Abuse Cocaine-Related Disorders
|
Cocaine
| null | 2
|
arm 1: 200mg progesterone twice daily arm 2: Placebo twice daily
|
[
1,
2
] | 2
|
[
0,
10
] |
intervention 1: 200mg progesterone twice daily intervention 2: placebo
|
intervention 1: Progesterone intervention 2: Placebo
| 1
|
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
| 0
|
NCT00218257
|
[
0
] | 12
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
Atomoxetine (Strattera) is a drug that is currently approved for treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Atomoxetine works to enhance levels of brain chemicals that may be affected in people with executive dysfunction, (difficulties with organization, task completion, and priority setting). Thus, atomoxetine has the potential to improve executive dysfunction in people with Parkinson's disease (PD).
The goal of this study is to provide preliminary data on the effectiveness and tolerability of atomoxetine for the treatment of executive dysfunction in patients with PD.
|
Parkinson's disease (PD), while defined by its motor abnormalities and associated dopaminergic loss, is invariably accompanied by cognitive impairment. Early in the disease course, the deficits are characterized by executive dysfunction with difficulties on tasks that involve information processing, attention, sorting, planning, set-shifting, and working memory and are subserved by neural connections with prefrontal brain regions. There has been little effort to identify treatments for these PD-related cognitive impairments, despite their disabling and distressing effects. Accordingly, the goal of this proposal is to conduct a small pilot study to determine the effectiveness and tolerability of atomoxetine, a selective norepinephrine reuptake inhibitor, for the treatment of executive dysfunction in patients with PD.
Atomoxetine (Strattera) is currently approved by the FDA for treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Atomoxetine enhances dopaminergic and noradrenergic transmission in frontal regions that are also implicated in executive dysfunction and thus has the potential to improve executive dysfunction in PD as well as other neurological conditions. Results of the study will be used to develop a larger placebo-controlled trial of atomoxetine, if appropriate, as well as inform the design of other clinical trials on potential treatments for cognitive dysfunction in PD.
The overall hypothesis is that atomoxetine will be an effective and safe treatment for executive dysfunction in PD.
|
Parkinson's Disease
|
Parkinson's disease executive dysfunction impairment motor skills cognitive
| null | 1
|
arm 1: Open-Label Uncontrolled Active Drug Intervention, No comparator
|
[
5
] | 1
|
[
0
] |
intervention 1: Open Label uncontrolled active Drug intervention
|
intervention 1: Atomoxetine
| 1
|
Baltimore | Maryland | United States | -76.61219 | 39.29038
| 0
|
NCT00286949
|
[
4
] | 4,128
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this clinical research study is to learn if Irbesartan is superior to placebo in reducing mortality and cardiovascular morbidity in subjects with heart failure with preserved systolic function. The safety of this treatment will also be studied.
| null |
Congestive Heart Failure
| null | 2
|
arm 1: None arm 2: None
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years intervention 2: Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years
|
intervention 1: Irbesartan intervention 2: Placebo
| 229
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Peoria | Arizona | United States | -112.23738 | 33.5806
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Los Angeles | California | United States | -118.24368 | 34.05223
San Diego | California | United States | -117.16472 | 32.71571
San Francisco | California | United States | -122.41942 | 37.77493
Farmington | Connecticut | United States | -72.83204 | 41.71982
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville Beach | Florida | United States | -81.39314 | 30.29469
Lake Worth | Florida | United States | -80.07231 | 26.61708
Tampa | Florida | United States | -82.45843 | 27.94752
Vero Beach | Florida | United States | -80.39727 | 27.63864
Chicago | Illinois | United States | -87.65005 | 41.85003
Peoria | Illinois | United States | -89.58899 | 40.69365
Jeffersonville | Indiana | United States | -85.73718 | 38.27757
Louisville | Kentucky | United States | -85.75941 | 38.25424
Chalmette | Louisiana | United States | -89.96537 | 29.94296
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Auburn | Maine | United States | -70.23117 | 44.09785
Takoma Park | Maryland | United States | -77.00748 | 38.97789
Towson | Maryland | United States | -76.60191 | 39.4015
Boston | Massachusetts | United States | -71.05977 | 42.35843
Haverhill | Massachusetts | United States | -71.07728 | 42.7762
Natick | Massachusetts | United States | -71.3495 | 42.28343
Detroit | Michigan | United States | -83.04575 | 42.33143
Petoskey | Michigan | United States | -84.95533 | 45.37334
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
St Louis | Missouri | United States | -90.19789 | 38.62727
Omaha | Nebraska | United States | -95.94043 | 41.25626
Reno | Nevada | United States | -119.8138 | 39.52963
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Elmer | New Jersey | United States | -75.17018 | 39.59511
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Albany | New York | United States | -73.75623 | 42.65258
East Syracuse | New York | United States | -76.07853 | 43.06534
Flushing | New York | United States | -73.81736 | 40.76538
Rochester | New York | United States | -77.61556 | 43.15478
The Bronx | New York | United States | -73.86641 | 40.84985
Troy | New York | United States | -73.69179 | 42.72841
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Concord | North Carolina | United States | -80.58158 | 35.40888
Durham | North Carolina | United States | -78.89862 | 35.99403
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Canton | Ohio | United States | -81.37845 | 40.79895
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Lorain | Ohio | United States | -82.18237 | 41.45282
Sandusky | Ohio | United States | -82.70796 | 41.44894
Portland | Oregon | United States | -122.67621 | 45.52345
Flourtown | Pennsylvania | United States | -75.2124 | 40.10344
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Charleston | South Carolina | United States | -79.93275 | 32.77632
Germantown | Tennessee | United States | -89.81009 | 35.08676
Austin | Texas | United States | -97.74306 | 30.26715
Lynchberg | Virginia | United States | N/A | N/A
Richmond | Virginia | United States | -77.46026 | 37.55376
South Boston | Virginia | United States | -78.9014 | 36.69875
Spokane | Washington | United States | -117.42908 | 47.65966
Madison | Wisconsin | United States | -89.40123 | 43.07305
Buenos Aires | Buenos Aires | Argentina | N/A | N/A
San Martín | Buenos Aires | Argentina | -57.75317 | -35.02575
Corrientes | Corrientes Province | Argentina | -58.8344 | -27.46784
Córdoba | Córdoba Province | Argentina | -64.18853 | -31.40648
Mendoza | Mendoza Province | Argentina | -68.84582 | -32.88946
Rosario | Santa Fe Province | Argentina | -60.63932 | -32.94682
Coffs Harbour | New South Wales | Australia | 153.11351 | -30.29626
Concord | New South Wales | Australia | 151.10381 | -33.84722
Garran | New South Wales | Australia | N/A | N/A
Kogarah | New South Wales | Australia | 151.13564 | -33.9681
Randwick | New South Wales | Australia | 151.24895 | -33.91439
Auchenflower | Queensland | Australia | 152.99213 | -27.47443
Brisbane | Queensland | Australia | 153.02809 | -27.46794
Woolloongabba | Queensland | Australia | 153.03655 | -27.48855
Launceston | Tasmania | Australia | 147.13467 | -41.43876
Geelong | Victoria | Australia | 144.36069 | -38.14711
Prahran | Victoria | Australia | 144.99318 | -37.85114
Aalst | N/A | Belgium | 4.0355 | 50.93604
Aye | N/A | Belgium | 5.30064 | 50.22471
Borgerhout | N/A | Belgium | 4.43539 | 51.20957
Genk-waterschei | N/A | Belgium | N/A | N/A
Ghent | N/A | Belgium | 3.71667 | 51.05
Hasselt | N/A | Belgium | 5.33781 | 50.93106
Huy | N/A | Belgium | 5.23284 | 50.51894
Leuven | N/A | Belgium | 4.70093 | 50.87959
Verviers | N/A | Belgium | 5.86241 | 50.58907
Salvador | Estado de Bahia | Brazil | -38.49096 | -12.97563
Goiania-go | Goiás | Brazil | N/A | N/A
Belo Horizonte | Minas Gerais | Brazil | -43.93778 | -19.92083
Rio de Janeiro | Rio de Janeiro | Brazil | -43.18223 | -22.90642
Campinas | São Paulo | Brazil | -47.06083 | -22.90556
Sao Paulo, Sp | São Paulo | Brazil | -46.63611 | -23.5475
Calgary | Alberta | Canada | -114.08529 | 51.05011
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Ajax | Ontario | Canada | -79.03288 | 43.85012
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Rexdale | Ontario | Canada | -79.57106 | 43.72087
Scarborough Village | Ontario | Canada | -79.22124 | 43.73899
Toronto | Ontario | Canada | -79.39864 | 43.70643
Weston | Ontario | Canada | -79.51513 | 43.70359
Longueuil | Quebec | Canada | -73.46818 | 45.5152
Montreal | Quebec | Canada | -73.58781 | 45.50884
Saint-Lambert | Quebec | Canada | -73.51028 | 45.50008
Ste-Foy | Quebec | Canada | N/A | N/A
Prague | N/A | Czechia | 14.42076 | 50.08804
Ústí nad Labem | N/A | Czechia | 14.03227 | 50.6607
Copenhagen | N/A | Denmark | 12.56553 | 55.67594
Copenhagen Nv | N/A | Denmark | N/A | N/A
Abbeville | N/A | France | 1.83547 | 50.10521
Cholet | N/A | France | -0.87974 | 47.05893
Dax | N/A | France | -1.05366 | 43.71032
Gap | N/A | France | 6.07868 | 44.55858
Langres | N/A | France | 5.33308 | 47.86263
Lille | N/A | France | 3.05858 | 50.63297
Montbéliard | N/A | France | 6.79823 | 47.50957
Paris | N/A | France | 2.3488 | 48.85341
Poissy | N/A | France | 2.04952 | 48.92902
Pontoise | N/A | France | 2.1 | 49.05
Provins | N/A | France | 3.29939 | 48.55897
Roubaix | N/A | France | 3.17456 | 50.69421
Rouen | N/A | France | 1.09932 | 49.44313
St-Malo | N/A | France | -2.00877 | 48.64738
Tours | N/A | France | 0.70398 | 47.39484
Vandœuvre-lès-Nancy | N/A | France | 6.17114 | 48.66115
Vichy | N/A | France | 3.42577 | 46.12709
Bad Homburg | N/A | Germany | 8.61816 | 50.22683
Berlin | N/A | Germany | 13.41053 | 52.52437
Göttingen | N/A | Germany | 9.93228 | 51.53443
Gunzenhausen | N/A | Germany | 10.75971 | 49.11663
Halle | N/A | Germany | 11.97947 | 51.48158
Homburg / Saar | N/A | Germany | N/A | N/A
Jena | N/A | Germany | 11.5899 | 50.92878
Langen | N/A | Germany | 8.66852 | 49.98955
Leipzig | N/A | Germany | 12.37129 | 51.33962
Mainz | N/A | Germany | 8.2791 | 49.98419
Marburg | N/A | Germany | 8.77069 | 50.80904
München | N/A | Germany | 13.31243 | 51.60698
Regensburg | N/A | Germany | 12.10161 | 49.01513
Stuttgart | N/A | Germany | 9.17702 | 48.78232
Witten | N/A | Germany | 7.35258 | 51.44362
Würzburg | N/A | Germany | 9.95121 | 49.79391
Athens | N/A | Greece | 23.72784 | 37.98376
Pátrai | N/A | Greece | 21.73444 | 38.24444
Budapest | N/A | Hungary | 19.04045 | 47.49835
Debrecen | N/A | Hungary | 21.62444 | 47.53167
Siófok | N/A | Hungary | 18.058 | 46.90413
Szeged | N/A | Hungary | 20.14824 | 46.253
County Dublin | Dublin | Ireland | N/A | N/A
Dublin | Dublin | Ireland | -6.24889 | 53.33306
Ascoli Piceno | N/A | Italy | 13.57395 | 42.85351
Bologna | N/A | Italy | 11.33875 | 44.49381
Brescia | N/A | Italy | 10.21472 | 45.53558
Cosenza | N/A | Italy | 16.25307 | 39.2989
Pavia | N/A | Italy | 9.15917 | 45.19205
Perugia | N/A | Italy | 12.38878 | 43.1122
Piacenza | N/A | Italy | 9.69342 | 45.05242
Roma | N/A | Italy | 11.10642 | 44.99364
Siena | N/A | Italy | 11.33064 | 43.31822
Trieste | N/A | Italy | 13.77678 | 45.64953
Udine | N/A | Italy | 13.23715 | 46.0693
Aguascalientes | Aguascalientes | Mexico | -102.2843 | 21.88262
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Mexico City | Mexico City | Mexico | -99.12766 | 19.42847
San Pedro Garza García | Nuevo León | Mexico | -100.40651 | 25.6604
Alkmaar | N/A | Netherlands | 4.74861 | 52.63167
Almere Stad | N/A | Netherlands | 5.21413 | 52.37025
Amersfoort | N/A | Netherlands | 5.3875 | 52.155
Apeldoorn | N/A | Netherlands | 5.96944 | 52.21
Assen | N/A | Netherlands | 6.5625 | 52.99667
Breda | N/A | Netherlands | 4.77596 | 51.58656
Delft | N/A | Netherlands | 4.35556 | 52.00667
Emmen | N/A | Netherlands | 6.90694 | 52.77917
Gorinchem | N/A | Netherlands | 4.97243 | 51.83652
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Heemstede | N/A | Netherlands | 4.62301 | 52.34992
Helmond | N/A | Netherlands | 5.66111 | 51.48167
Hengelo Ov | N/A | Netherlands | N/A | N/A
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Sittard | N/A | Netherlands | 5.86944 | 50.99833
Sneek | N/A | Netherlands | 5.6589 | 53.03297
Veldhoven | N/A | Netherlands | 5.40278 | 51.41833
Vlaardingen | N/A | Netherlands | 4.34167 | 51.9125
Zaandam | N/A | Netherlands | 4.82643 | 52.43854
Baerum Postterminal | N/A | Norway | N/A | N/A
Stavanger | N/A | Norway | 5.73332 | 58.97005
Tønsberg | N/A | Norway | 10.40762 | 59.26754
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Katowice | N/A | Poland | 19.02754 | 50.25841
Piotrkow Tryb. | N/A | Poland | N/A | N/A
Stalowa Wola | N/A | Poland | 22.05334 | 50.58286
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Matosinhos Municipality | N/A | Portugal | -8.68908 | 41.18207
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saratov | N/A | Russia | 46.00861 | 51.54056
Johannesburg | Gauteng | South Africa | 28.04363 | -26.20227
Morningside | Gauteng | South Africa | 28.06286 | -26.0793
Parktown West | Gauteng | South Africa | N/A | N/A
Berea | KwaZulu-Natal | South Africa | 30.99337 | -29.85185
KwaKhangela | KwaZulu-Natal | South Africa | 30.99535 | -29.87931
A Coruña | N/A | Spain | -8.396 | 43.37135
Barcelona | N/A | Spain | 2.15899 | 41.38879
Córdoba | N/A | Spain | -4.77275 | 37.89155
Madrid | N/A | Spain | -3.70256 | 40.4165
Málaga | N/A | Spain | -4.42034 | 36.72016
Murcia | N/A | Spain | -1.13004 | 37.98704
Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939
Seville | N/A | Spain | -5.97317 | 37.38283
Valencia | N/A | Spain | -0.37966 | 39.47391
Zaragoza | N/A | Spain | -0.87734 | 41.65606
Falun | N/A | Sweden | 15.62597 | 60.60357
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Linköping | N/A | Sweden | 15.62157 | 58.41086
Malmo | N/A | Sweden | 13.00073 | 55.60587
Skellefteå | N/A | Sweden | 20.95279 | 64.75067
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Sundsvall | N/A | Sweden | 17.3063 | 62.39129
Bellinzona | N/A | Switzerland | 9.01703 | 46.19278
Liestal | N/A | Switzerland | 7.73446 | 47.48455
Zurich | N/A | Switzerland | 8.55 | 47.36667
Glasgow | Dumbartonshire | United Kingdom | -4.25763 | 55.86515
Romford | Essex | United Kingdom | 0.18582 | 51.57515
Londonderry | Londonderry | United Kingdom | -7.30934 | 54.9981
Hull | Yorkshire | United Kingdom | -0.33525 | 53.7446
York | Yorkshire | United Kingdom | -1.08271 | 53.95763
Dundee | N/A | United Kingdom | -2.97489 | 56.46913
| 1
|
NCT00095238
|
|
[
4
] | 831
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| true
|
Schizophrenia is a brain disease. The condition may be associated with acute psychotic episodes and long-term disability despite remission from the acute symptoms. Current management of schizophrenia focuses on the treatment of acute symptoms as well as long-term treatment aimed at preventing relapse after patients have experienced an improvement in acute symptoms. Patients who discontinue treatment have a high likelihood of experiencing relapse within 1-2 years after an acute episode of schizophrenia. Patients who remain on antipsychotic treatment have lower rates of relapse and have milder courses of exacerbation when relapse occurs.The symptoms of schizophrenia may be due to an imbalance in chemicals in the brain, primarily dopamine and serotonin, which enables brain cells to communicate with each other. Asenapine may help to correct the imbalance in dopamine and serotonin. The purpose of this clinical trial is to evaluate the efficacy of asenapine in preventing relapse/impending relapse (hereafter referred to as 'relapse') in subjects who have been treated with asenapine for symptoms of schizophrenia for 26 weeks. In addition, to determine the safety and tolerability of asenapine for up to 1-year of treatment.
| null |
Schizophrenia
| null | 2
|
arm 1: None arm 2: None
|
[
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: Open Label Phase: All subjects received 26 weeks of open label asenapine treatment (cross titration period up to first 4 weeks, with target dose of 10 mg twice daily by week 1). intervention 2: Double Blind Phase: Following Open Label Phase, matching placebo sublingual twice daily for 26 weeks. intervention 3: Double Blind Phase: Following the Open Label Phase, asenapine 5 or 10 mg sublingual twice daily for 26 weeks.
|
intervention 1: Asenapine - Open Label intervention 2: Placebo - Double Blind intervention 3: Asenapine - Double Blind
| 0
| null | 1
|
NCT00150176
|
|
[
5
] | 359
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
To assess motor function and quality of life (QoL) in Parkinson's disease (PD) subjects with end-of-dose wearing off, comparing immediate and delayed switch to carbidopa/levodopa and entacapone.
|
This was a prospective, multi-center, randomized, open-label study with blinded raters to evaluate the effects of immediate versus delayed switch to carbidopa/levodopa/entacapone on motor function and quality of life in patients with Parkinson's disease with end-of-dose wearing off.
|
Parkinson's Disease With End of Dose Wearing Off
|
Parkinson's disease, tremor
| null | 2
|
arm 1: Patients were switched the day after randomization from combined carbidopa/levodopa to combined carbidopa/levodopa/entacapone. Patients received the same doses of carbidopa (12.5, 25.0, or 37.5 mg) and levodopa (50, 100, or 150 mg) they were receiving prior to the switch, combined with 200 mg of entacapone. The frequency of doses per day prior to the switch remained the same after the switch. arm 2: Patients were switched 4 weeks after randomization from combined carbidopa/levodopa to combined carbidopa/levodopa/entacapone. Patients received the same doses of carbidopa (12.5, 25.0, or 37.5 mg) and levodopa (50, 100, or 150 mg) they were receiving prior to the switch, combined with 200 mg of entacapone. The frequency of doses per day prior to the switch remained the same after the switch.
|
[
0,
1
] | 1
|
[
0
] |
intervention 1: Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to carbidopa/levodopa/entacapone.
|
intervention 1: Carbidopa/levodopa/entacapone
| 42
|
Phoenix | Arizona | United States | -112.07404 | 33.44838
Fullerton | California | United States | -117.92534 | 33.87029
Irvine | California | United States | -117.82311 | 33.66946
La Jolla | California | United States | -117.2742 | 32.84727
Los Angeles | California | United States | -118.24368 | 34.05223
Pasadena | California | United States | -118.14452 | 34.14778
Reseda | California | United States | -118.53647 | 34.20112
Stanford | California | United States | -122.16608 | 37.42411
Fort Collins | Colorado | United States | -105.08442 | 40.58526
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Boca Raton | Florida | United States | -80.0831 | 26.35869
Bradenton | Florida | United States | -82.57482 | 27.49893
Fort Lauderdale | Florida | United States | -80.14338 | 26.12231
Hollywood | Florida | United States | -80.14949 | 26.0112
Naples | Florida | United States | -81.79596 | 26.14234
Palm Beach | Florida | United States | -80.03643 | 26.70562
Plantation | Florida | United States | -80.23184 | 26.13421
Pompano Beach | Florida | United States | -80.12477 | 26.23786
Port Charlotte | Florida | United States | -82.09064 | 26.97617
Chicago | Illinois | United States | -87.65005 | 41.85003
Flossmoor | Illinois | United States | -87.68477 | 41.54281
Lenexa | Kansas | United States | -94.73357 | 38.95362
Topeka | Kansas | United States | -95.67804 | 39.04833
Baltimore | Maryland | United States | -76.61219 | 39.29038
Bingham Farms | Michigan | United States | -83.27326 | 42.51587
Southfield | Michigan | United States | -83.22187 | 42.47337
Hattiesburg | Mississippi | United States | -89.29034 | 31.32712
Columbia | Missouri | United States | -92.33407 | 38.95171
St Louis | Missouri | United States | -90.19789 | 38.62727
Ridgewood | New Jersey | United States | -74.11653 | 40.97926
Commack | New York | United States | -73.29289 | 40.84288
Durham | North Carolina | United States | -78.89862 | 35.99403
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Bellevue | Ohio | United States | -82.84158 | 41.27366
Canton | Ohio | United States | -81.37845 | 40.79895
Tualatin | Oregon | United States | -122.76399 | 45.38401
East Stroudsburg | Pennsylvania | United States | -75.18129 | 40.99954
Houston | Texas | United States | -95.36327 | 29.76328
Spokane | Washington | United States | -117.42908 | 47.65966
Tacoma | Washington | United States | -122.44429 | 47.25288
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Caroline | N/A | Puerto Rico | N/A | N/A
| 1
|
NCT00219284
|
[
4
] | 251
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The main purpose of this study is to establish an optimal monitoring regimen in NutropinAq treated children, using newly developed capillary blood spot IGF-1 measurement technology.
| null |
Turner Syndrome Renal Insufficiency, Chronic Pituitary Diseases Dwarfism
|
growth child development growth hormone inadequate growth hormone secretion growth failure
| null | 1
|
arm 1: Patients received daily subcutaneous (s.c.) injections of NutropinAq 10 milligrams (mg)/2 milliliters (mL) for 6 months. The therapeutic daily doses administered were as follows:
* GHD patients: 0.025 - 0.035 mg/ kilogram (kg) bodyweight
* TS patients: up to 0.05 mg/kg bodyweight
* CRI patients: up to 0.05 mg/kg bodyweight
Patients visited the study clinic for a baseline visit and for 2 other visits every 3 months (Weeks 12 and 24). Additional home assessments were made at Weeks 21, 22 and 23.
The investigator determined the dose administered to each patient, and it was recommended to perform the injection in the evening.
|
[
0
] | 1
|
[
0
] |
intervention 1: Daily subcutaneous injections, 0,025 - 0,05 mg/kg/day for 6 months.
|
intervention 1: Somatropin (rDNA origin)
| 45
|
Brussels | N/A | Belgium | 4.34878 | 50.85045
Edegem | N/A | Belgium | 4.44504 | 51.15662
Prague | N/A | Czechia | 14.42076 | 50.08804
Aalborg | N/A | Denmark | 9.9187 | 57.048
Herning | N/A | Denmark | 8.97662 | 56.13615
Helsinki | N/A | Finland | 24.93545 | 60.16952
Angers | N/A | France | -0.55202 | 47.47156
Bordeaux | N/A | France | -0.5805 | 44.84044
Grenoble | N/A | France | 5.71479 | 45.17869
Le Havre | N/A | France | 0.10785 | 49.49346
Marseille | N/A | France | 5.38107 | 43.29695
Montpellier | N/A | France | 3.87635 | 43.61093
Nice | N/A | France | 7.26608 | 43.70313
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Rouen | N/A | France | 1.09932 | 49.44313
Strasbourg | N/A | France | 7.74553 | 48.58392
Tarbes | N/A | France | 0.07139 | 43.23407
Toulouse | N/A | France | 1.44367 | 43.60426
Toulouse | N/A | France | 1.44367 | 43.60426
Tours | N/A | France | 0.70398 | 47.39484
Leipzig | N/A | Germany | 12.37129 | 51.33962
Tübingen | N/A | Germany | 9.05222 | 48.52266
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Catania | N/A | Italy | 15.07041 | 37.49223
Chieti | N/A | Italy | 14.16494 | 42.34827
Florence | N/A | Italy | 11.24626 | 43.77925
Napoli | N/A | Italy | 14.5195 | 40.87618
Napoli | N/A | Italy | 14.5195 | 40.87618
Novara | N/A | Italy | 8.62118 | 45.44694
Parma | N/A | Italy | 10.32618 | 44.79935
Bucharest | N/A | Romania | 26.10626 | 44.43225
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Barcelona | N/A | Spain | 2.15899 | 41.38879
Elche | N/A | Spain | -0.70107 | 38.26218
Madrid | N/A | Spain | -3.70256 | 40.4165
Sabadell | N/A | Spain | 2.10942 | 41.54329
Santiago de Compostela | N/A | Spain | -8.54569 | 42.88052
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
London | England | United Kingdom | -0.12574 | 51.50853
Cardiff | Wales | United Kingdom | -3.18 | 51.48
| 1
|
NCT00234533
|
[
3,
4
] | 451
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
Phase 2/3 open-label trial to assess the safety and tolerability of long-term treatment with lacosamide (SPM 927) in subjects with painful diabetic neuropathy. The safety and tolerability of the different doses of lacosamide will be investigated.
|
This phase 2/3 open-label trial is being conducted at approximately 100 sites in the US to assess the safety and tolerability of long-term treatment with lacosamide (SPM 927) in subjects with painful diabetic neuropathy. Approximately 525 subjects will be enrolled. To qualify for this trial, subjects with symptoms of painful distal diabetic neuropathy ranging in duration from 6 months to 5 years must have completed trials SP665, SP742, or SP768 and, in the investigator's opinion, may benefit from long-term administration of lacosamide. Subjects will be titrated to their optimal dose of lacosamide (up to 600mg/day). The safety and tolerability of the different doses of lacosamide will be investigated throughout the trial. In addition, to determine what effect lacosamide has on diabetic neuropathic pain, subjects will use a diary to record their daily pain intensity and pain interference with sleep and activity. Subjects' quality of life will also be investigated.
|
Diabetic Neuropathy
|
Painful Distal Diabetic Neuropathy
| null | 1
|
arm 1: Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day
|
[
0
] | 1
|
[
0
] |
intervention 1: Open-label treatment (two times per day) with film-coated tablets include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, and 600mg/day throughout individual study period.
|
intervention 1: lacosamide
| 84
|
Anniston | Alabama | United States | -85.83163 | 33.65983
Hoover | Alabama | United States | -86.81138 | 33.40539
Huntsville | Alabama | United States | -86.58594 | 34.7304
Northport | Alabama | United States | -87.57723 | 33.22901
Tuscaloosa | Alabama | United States | -87.56917 | 33.20984
Peoria | Arizona | United States | -112.23738 | 33.5806
Phoenix | Arizona | United States | -112.07404 | 33.44838
Tucson | Arizona | United States | -110.92648 | 32.22174
Hot Springs | Arkansas | United States | -93.05518 | 34.5037
Jonesboro | Arkansas | United States | -90.70428 | 35.8423
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Irvine | California | United States | -117.82311 | 33.66946
Los Angeles | California | United States | -118.24368 | 34.05223
San Diego | California | United States | -117.16472 | 32.71571
Santa Monica | California | United States | -118.49138 | 34.01949
Spring Valley | California | United States | -116.99892 | 32.74477
Tustin | California | United States | -117.82617 | 33.74585
Walnut Creek | California | United States | -122.06496 | 37.90631
Denver | Colorado | United States | -104.9847 | 39.73915
Stratford | Connecticut | United States | -73.13317 | 41.18454
Newark | Delaware | United States | -75.74966 | 39.68372
Wilmington | Delaware | United States | -75.54659 | 39.74595
Bradenton | Florida | United States | -82.57482 | 27.49893
Clearwater | Florida | United States | -82.8001 | 27.96585
Fort Myers | Florida | United States | -81.84059 | 26.62168
New Port Richey | Florida | United States | -82.71927 | 28.24418
Ocala | Florida | United States | -82.14009 | 29.1872
Pembroke Pines | Florida | United States | -80.22394 | 26.00315
Pinellas Park | Florida | United States | -82.69954 | 27.8428
South Miami | Florida | United States | -80.29338 | 25.7076
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Sunrise | Florida | United States | -80.1131 | 26.13397
Tallahassee | Florida | United States | -84.28073 | 30.43826
Marietta | Georgia | United States | -84.54993 | 33.9526
Chicago | Illinois | United States | -87.65005 | 41.85003
Elk Grove Village | Illinois | United States | -87.97035 | 42.00392
North Chicago | Illinois | United States | -87.84118 | 42.32558
Evansville | Indiana | United States | -87.55585 | 37.97476
West Des Moines | Iowa | United States | -93.71133 | 41.57721
Crestview Hills | Kentucky | United States | -84.58494 | 39.02728
Louisville | Kentucky | United States | -85.75941 | 38.25424
Madisonville | Kentucky | United States | -87.49889 | 37.3281
Paducah | Kentucky | United States | -88.60005 | 37.08339
Owings Mills | Maryland | United States | -76.78025 | 39.41955
Towson | Maryland | United States | -76.60191 | 39.4015
Brockton | Massachusetts | United States | -71.01838 | 42.08343
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
St Louis | Missouri | United States | -90.19789 | 38.62727
Great Falls | Montana | United States | -111.30081 | 47.50024
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Lawrenceville | New Jersey | United States | -74.7296 | 40.29733
Voorhees Township | New Jersey | United States | -74.49062 | 40.4795
Albany | New York | United States | -73.75623 | 42.65258
Mineola | New York | United States | -73.64068 | 40.74927
White Plains | New York | United States | -73.76291 | 41.03399
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Greenville | North Carolina | United States | -77.36635 | 35.61266
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Toledo | Ohio | United States | -83.55521 | 41.66394
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Medford | Oregon | United States | -122.87559 | 42.32652
Portland | Oregon | United States | -122.67621 | 45.52345
Upland | Pennsylvania | United States | -75.38269 | 39.85261
Greer | South Carolina | United States | -82.22706 | 34.93873
Bristol | Tennessee | United States | -82.18874 | 36.59511
Nashville | Tennessee | United States | -86.78444 | 36.16589
Amarillo | Texas | United States | -101.8313 | 35.222
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Worth | Texas | United States | -97.32085 | 32.72541
Houston | Texas | United States | -95.36327 | 29.76328
Richardson | Texas | United States | -96.72972 | 32.94818
San Antonio | Texas | United States | -98.49363 | 29.42412
Bennington | Vermont | United States | -73.19677 | 42.87813
Richmond | Virginia | United States | -77.46026 | 37.55376
Salem | Virginia | United States | -80.05476 | 37.29347
Virginia Beach | Virginia | United States | -75.97799 | 36.85293
Spokane | Washington | United States | -117.42908 | 47.65966
Tacoma | Washington | United States | -122.44429 | 47.25288
Wenatchee | Washington | United States | -120.31035 | 47.42346
| 1
|
NCT00235443
|
[
4
] | 1,123
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to evaluate the safety profile of tapentadol (CG5503) PR at doses of 100 mg - 250 mg administered twice daily over a maximum one year period to patients with at least a 3-month history of low back pain, or pain caused by knee or hip osteoarthritis.
|
Tapentadol (CG5503) is a centrally active pain-relieving drug being investigated for the treatment of acute and chronic pain. This study is a randomized (patients are assigned different treatments based on chance in a ratio of 4 patients on tapentadol (CG5503) PR to every 1 patient on oxycodone CR), open-label (both the Investigator and the patient know what medication is allocated), active-controlled, parallel-group, multicenter study. It is designed to investigate the long-term safety (side effects during up to one year of administration) and effectiveness (level of pain control) of tapentadol (CG5503) PR compared to oxycodone CR (an opioid commonly used for relief of moderate to severe pain) taken orally. The study consisted of a screening period (up to 14 days), a washout period (3 to 7 days), and an active treatment phase with titration and maintenance (total duration of 52 weeks). The doses of both of these medications will be adjusted to give the best therapeutic benefit for the patient. A total of 1123 patients will be screened. Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Assessments of pain relief include the pain intensity numerical rating scale, and patient global impression of change scale (PGIC). Venous blood samples will be collected for the determination of serum concentrations of tapentadol (CG5503) and oxycodone. Tapentadol (CG5503) PR is also referred to as Tapentadol (CG5503) Extended Release (ER). Starting oral dose is randomly assigned to tapentadol (CG5503) PR 50 mg or oxycodone CR 10 mg twice daily (BID) x 3 days; then increase to tapentadol (CG5503)100 mg BID, oxycodone CR 20 mg BID x 4 days; during the maintenance phase upward titration may occur at a minimum of 3 day intervals in increments of tapentadol (CG5503) PR 50 mg BID or oxycodone CR 10 mg BID. The maximum doses are tapentadol (CG5503) PR 250 mg BID or oxycodone CR 50 mg BID.
|
Osteoarthritis, Hip Osteoarthritis, Knee Lower Back Pain Pain
|
Osteoarthritis Pain Low Back Pain Hip Pain Knee Pain Backache Tapentadol
| null | 2
|
arm 1: Tapentadol (CG5503) extended release (ER) 100 to 250 mg twice daily (BID) for up to one year. arm 2: Oxycodone controlled release (CR) 20 to 50 mg twice daily (BID) for up to one year.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: Oxycodone CR 10 mg oral tablet BID administered for first 3 days, 20 mg oral tablet BID administered for next 4 days, 20 to 50 mg oral tablet BID administered for the next 51 weeks. intervention 2: Tapentadol (CG5503) ER 50 mg oral tablet BID administered for first 3 days, 100 mg oral tablet BID administered for next 4 days, 100 to 250 mg oral tablet BID administered for the next 51 weeks.
|
intervention 1: Oxycodone CR intervention 2: Tapentadol (CG5503) ER
| 52
|
Mesa | Arizona | United States | -111.82264 | 33.42227
Tucson | Arizona | United States | -110.92648 | 32.22174
Anaheim | California | United States | -117.9145 | 33.83529
Cudahy | California | United States | -118.18535 | 33.96057
Encinitas | California | United States | -117.29198 | 33.03699
San Diego | California | United States | -117.16472 | 32.71571
Westlake Village | California | United States | -118.80565 | 34.14584
Trumbull | Connecticut | United States | -73.20067 | 41.24287
Chiefland | Florida | United States | -82.85984 | 29.47496
Clearwater | Florida | United States | -82.8001 | 27.96585
Jacksonville | Florida | United States | -81.65565 | 30.33218
Oldsmar | Florida | United States | -82.6651 | 28.03418
Atlanta | Georgia | United States | -84.38798 | 33.749
Cumming | Georgia | United States | -84.14019 | 34.20732
Decatur | Georgia | United States | -84.29631 | 33.77483
Perry | Georgia | United States | -83.73157 | 32.45821
Suwanee | Georgia | United States | -84.0713 | 34.05149
Woodstock | Georgia | United States | -84.51938 | 34.10149
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Prairie Village | Kansas | United States | -94.63357 | 38.99167
Topeka | Kansas | United States | -95.67804 | 39.04833
Paducah | Kentucky | United States | -88.60005 | 37.08339
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Rockville | Maryland | United States | -77.15276 | 39.084
Wellesley Hills | Massachusetts | United States | -71.27867 | 42.30843
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Mamaroneck | New York | United States | -73.73263 | 40.94871
Williamsville | New York | United States | -78.73781 | 42.96395
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Kettering | Ohio | United States | -84.16883 | 39.6895
Medford | Oregon | United States | -122.87559 | 42.32652
Duncansville | Pennsylvania | United States | -78.4339 | 40.42341
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Greenville | South Carolina | United States | -82.39401 | 34.85262
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Roanoke | Virginia | United States | -79.94143 | 37.27097
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Coquitlam | British Columbia | Canada | -122.78217 | 49.2846
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Corunna | Ontario | Canada | -82.43313 | 42.88338
Greater Sudbury | Ontario | Canada | -80.99001 | 46.49
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Sarnia | Ontario | Canada | -82.40407 | 42.97866
Toronto | Ontario | Canada | -79.39864 | 43.70643
Vancouver | Ontario | Canada | N/A | N/A
Pointe-Claire | Quebec | Canada | -73.81669 | 45.44868
Trois-Rivières | Quebec | Canada | -72.5477 | 46.34515
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
| 1
|
NCT00361504
|
[
4
] | 601
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
Assessment of the long-term safety and tolerability of the combination of aliskiren and valsartan (300 mg/ 320 mg) in patients with high blood pressure,followed by assessment of long-term safety and tolerability of the combination of aliskiren/valsartan/Hydrochlorothiazide(HCTZ).
| null |
Hypertension
|
Hypertension, aliskiren, valsartan, HCTZ, blood pressure
| null | 2
|
arm 1: Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combination for 52-weeks, optional addition of Hydrochlorothiazide (HCTZ) 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (mean sitting Systolic Blood Pressure ≥ 140 and/or mean sitting Diastolic Blood Pressure ≥ 90 mmHg). The dose of Hydrochlorothiazide (HCTZ) 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled. arm 2: For patients entering into extension, those previously treated with Hydrochlorothiazide (HCTZ) 12.5 or 25 mg in addition to aliskiren 300 mg/valsartan 320 mg were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 25 mg in the extension. Those patients who had not received HCTZ during the core study were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 12.5 mg.
The HCTZ 12.5 mg dose could be increased to HCTZ 25 mg if the mean sitting Systolic Blood Pressure (msSBP) was ≥140 mmHg and/or the mean sitting Diastolic Blood Pressure (msDBP) was ≥90 mmHg for 2 consecutive visits.
|
[
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Aliskiren 300 mg intervention 2: Valsartan 320 mg intervention 3: Hydrochlorothiazide (HCTZ) 12.5-25 mg
|
intervention 1: Aliskiren intervention 2: Valsartan intervention 3: Hydrochlorothiazide (HCTZ)
| 4
|
San Diego | California | United States | -117.16472 | 32.71571
Canada | N/A | Canada | N/A | N/A
Germany | N/A | Germany | N/A | N/A
Netherlands | N/A | Netherlands | N/A | N/A
| 1
|
NCT00386607
|
[
4
] | 330
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The trial was conducted in Germany, The Republic of Macedonia, Russian Federation, Serbia and South Africa. The aim of this trial was to make a safety comparison of insulin detemir produced by a new production method (NN729) with insulin detemir made by the previous production method (NN304). Subjects were treated with NN729 or NN304 for a period of 52 weeks at the same total daily dose and frequency of administration as their own pre-trial basal insulin . During the trial doses were individualised based on subject's plasma glucose measurements.
| null |
Diabetes Diabetes Mellitus, Type 1
| null | 2
|
arm 1: Individually adjusted dosage of insulin detemir produced by the NN304 process, administered sub-cutaneously (s.c.) 1-2 times daily + Individually adjusted dosage of insulin aspart, administered sub-cutaneously (s.c.) at meals for 52 weeks arm 2: Individually adjusted dosage of insulin detemir produced by the NN729 process, administered sub-cutaneously (s.c.) 1-2 times daily + Individually adjusted dosage of insulin aspart, administered sub-cutaneously (s.c.) at meals for 52 weeks
|
[
1,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: NN304 injected s.c. (under the skin). Given as basal insulin. intervention 2: Injected s.c. (under the skin). Given as bolus insulin. intervention 3: NN729 injected s.c. (under the skin). Given as basal insulin
|
intervention 1: insulin detemir intervention 2: insulin aspart intervention 3: insulin detemir
| 5
|
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Skopje | N/A | North Macedonia | 21.43141 | 41.99646
Moscow | N/A | Russia | 37.61556 | 55.75222
Belgrade | N/A | Serbia and Montenegro | N/A | N/A
Cape Town | Western Cape | South Africa | 18.42322 | -33.92584
| 1
|
NCT00447382
|
|
[
3
] | 199
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 4QUADRUPLE
| true
| 1FEMALE
| false
|
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of LY353381 may be an effective way to prevent the development of breast cancer in women who have hyperplasia.
PURPOSE: Randomized phase II trial to study the effectiveness of LY353381 in preventing breast cancer in women who have hyperplasia.
|
OBJECTIVES:
* Determine if LY353381 hydrochloride improves baseline cytology in women at high risk for breast cancer.
* Determine if this drug modulates other potential surrogate endpoint biomarkers or drug effect biomarkers.
* Determine if cytologic improvement is associated with initial presentation of the various stratification factors.
* Determine whether cytology is correlated with other potential surrogate endpoint biomarkers or drug effect biomarkers and whether change in cytology is correlated with change in the other biomarkers.
* Monitor the effects of this drug in terms of quality of life and women's health.
OUTLINE: This is a randomized, double-blind, multicenter study followed by an open-label study for both arms. Patients are stratified according to cytologic status (hyperplasia with atypia vs hyperplasia without atypia), mutation status (known carrier for BRCA1 or BRCA2 genes vs known not to be a carrier of mutant genes), menopausal status (premenopausal vs postmenopausal), estrogen-receptor status, and participating center. Patients are randomized to one of two treatment arms.
* Arm I: Patients receive oral LY353381 hydrochloride once daily for 6 months.
* Arm II: Patients receive oral placebo once daily for 6 months. Patients in both arms then receive oral LY353381 hydrochloride for an additional 6 months.
Quality of life is assessed at baseline and then at 6 and 12 months.
Patients are followed at 2 weeks and then annually for 5 years.
PROJECTED ACCRUAL: A total of 210-220 patients will be accrued for this study within 2.5-3 years.
|
Breast Cancer
|
breast cancer
| null | 2
|
arm 1: Placebo arm 2: LY353381, 20 mg daily
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: one tablet daily intervention 2: matched tablet dialy
|
intervention 1: arzoxifene intervention 2: Placebo
| 2
|
Kansas City | Kansas | United States | -94.62746 | 39.11417
Dallas | Texas | United States | -96.80667 | 32.78306
| 0
|
NCT00005879
|
[
2,
3
] | 39
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 1SINGLE
| false
| 0ALL
| true
|
This study will evaluate electroconvulsive therapy (ECT) in patients who have not responded adequately to clozapine.
|
ECT augmentation of clozapine will be compared to clozapine monotherapy in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.
|
Schizophrenia
|
Electroconvulsive Therapy
| null | 2
|
arm 1: Electroconvulsive therapy ECT plus clozapine for 8 weeks arm 2: Clozapine for 8 weeks
|
[
0,
1
] | 2
|
[
3,
0
] |
intervention 1: ECT will be used to augment clozapine in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine. intervention 2: Patients with psychotic symptoms will receive clozapine
|
intervention 1: Electroconvulsive Therapy (ECT) intervention 2: Clozapine
| 1
|
Glen Oaks | New York | United States | -73.71152 | 40.74705
| 0
|
NCT00042224
|
[
3
] | 150
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
The purpose of this study is to assess the utility of nitric oxide for inhalation during left ventricular assist device (LVAD) implantation following cardiopulmonary bypass (CPB). This is to be assessed by the number of patients in each treatment group meeting failure criteria within 24 hours on study drug, as defined by two or more of the following:
* Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m\^2
* Administration of ≥ 20 inotropic equivalents (IE)
* 10 µg/kg/min dopamine, dobutamine, enoximone or amrinone is equivalent to 10 IE
* 0.1 µg/kg/min epinephrine or norepinephrine is equivalent to 10 IE
* 1 µg/kg/min milrinone is equivalent to 15 IE
* 0.1 U/min vasopressin is equivalent to 10 IE
* Mean arterial pressure (MAP) ≤ 55 mmHg
* Central venous pressure (CVP) ≥ 16 mmHg
* Percent mixed venous oxygen saturation (SvO2) ≤ 55%
Or at least one of the following criteria:
* Failure to wean from cardiopulmonary bypass at least once due to hemodynamic failure. Re-initiation of cardiopulmonary bypass to correct bleeding or other technical issues will not be considere 'failure to wean'
* Death
|
40 ppm of either nitric oxide for inhalation or N2 (placebo) will be continuously administered to the patient starting at least 5 minutes prior to initiating the first weaning attempt from CPB and continue until the patient is either extubated, has reached failure criteria, or has been treated with study drug for 48 hours following discontinuation of CPB, whichever come first.
All patients will be monitored peri-operatively with a pulmonary arterial line, central venous line, and systemic arterial line. Baseline data collection by a designated clinical staff member will begin following induction of anesthesia and prior to skin incision. Following a successful wean from cardiopulmonary bypass, post-op data will be collected within 1 hour following end time of surgery. Data will then be collected at 6, 12, 18, 24, and 48 hours from post-op or until extubation, in which case weaning from study drug will begin.
Open label investigational nitric oxide for inhalation may be administered once a patient meets a minimum of two of the failure criteria or fails to wean at least once due to hemodynamic failure from cardiopulmonary bypass.
|
Congestive Heart Failure
|
Left Ventricular Assist Device Implantation Progressive Left Ventricular Failure
| null | 2
|
arm 1: Inhaled Nitric Oxide (iNO) at 40 parts per million (ppm) arm 2: Nitrogen (N2) administered at 40 ppm.
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: 40 ppm of Nitric Oxide continuously administered for 48 hours intervention 2: Nitrogen (N2) administered at 40 ppm for 48 hours
|
intervention 1: Nitric Oxide intervention 2: Nitrogen
| 11
|
Newark | New Jersey | United States | -74.17237 | 40.73566
Durham | North Carolina | United States | -78.89862 | 35.99403
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cleveland | Ohio | United States | -81.69541 | 41.4995
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
Gergstrab | Bad Oeynhausen | Germany | N/A | N/A
Augustenburger Platz | State of Berlin | Germany | N/A | N/A
Harefield | Middlesex | United Kingdom | -0.48546 | 51.60333
| 0
|
NCT00060840
|
[
3
] | 140
|
RANDOMIZED
|
FACTORIAL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
The purpose of this study is to determine whether the combination of cognitive-behavioral treatment and nortriptyline are more effective than each treatment alone in reducing the pain and disability associated with TMD.
|
This is a randomized, controlled trial evaluating pharmacological (nortriptyline vs. active placebo - benztropine) and psychological (cognitive-behavioral therapy vs. disease education) treatments for pain and disability due to temporomandibular joint disorder (TMD). Patients 18 to 65 years old meeting RDC criteria for TMD and other eligibility criteria complete a 3-week baseline monitoring phase prior to randomization. Active treatment consists of weekly visits for 8 week, then maintenance treatment for 6 months. Outcome measures include pain, physical and psychosocial function and are assessed at post-treatment, 3-months, and 6-months
|
Temporomandibular Joint Disorders
| null | 4
|
arm 1: Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT. arm 2: Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT. arm 3: Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management. arm 4: Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
|
[
0,
0,
0,
1
] | 4
|
[
0,
0,
5,
5
] |
intervention 1: Nortriptyline will be titrated up from 25 mg qhs to a maximum dose of 150 mg qhs based on treatment response and side effect profile. intervention 2: Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. intervention 3: Six in-person, individual sessions of cognitive-behavioral therapy for pain management include relaxation training, pain coping skills training, cognitive therapy for negative and dysfunctional thoughts, and diaries for monitoring relaxation, goals, and negative thinking. intervention 4: Six in-person, individual sessions of temporomandibular joint disorder (TMD) disease management (MGT) that include information about the jaw and good oral habits, diet, sleep, and general stress management.
|
intervention 1: Nortriptyline Oral Capsule intervention 2: Benztropine Oral Product intervention 3: CBT intervention 4: Disease MGT
| 1
|
Baltimore | Maryland | United States | -76.61219 | 39.29038
| 0
|
NCT00066937
|
|
[
3
] | 131
|
RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This study was designed to evaluate and compare the efficacy of two dose schedules of an oral investigational drug for the treatment of advanced or metastatic non-small cell lung cancer.
| null |
Lung Cancer, Non-Small Cell
|
EGFR ErbB1 ErbB2 metastatic lapatinib Her-2/neu protein kinase inhibitor BAC GW572016 Advanced NSCLC
| null | 1
|
arm 1: Randomized, open-label, parallel group, 2-stage study to evaluate and compare 2 dose schedules (1500 mg once daily and 500 mg twice daily) of oral lapatinib.
|
[
5
] | 1
|
[
0
] |
intervention 1: tyrosine kinase inhibitor
|
intervention 1: GW572016 (lapatinib)
| 31
|
Jasper | Alabama | United States | -87.27751 | 33.83122
Greenbrae | California | United States | -122.5247 | 37.94854
La Jolla | California | United States | -117.2742 | 32.84727
Long Beach | California | United States | -118.18923 | 33.76696
Poway | California | United States | -117.03586 | 32.96282
Rancho Mirage | California | United States | -116.41279 | 33.73974
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Gainsville | Florida | United States | N/A | N/A
Elk Grove Village | Illinois | United States | -87.97035 | 42.00392
Houma | Louisiana | United States | -90.71953 | 29.59577
Metairie | Louisiana | United States | -90.15285 | 29.98409
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
Santa Fe | New Mexico | United States | -105.9378 | 35.68698
Nyack | New York | United States | -73.91791 | 41.09065
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Durham | North Carolina | United States | -78.89862 | 35.99403
Cleveland | Ohio | United States | -81.69541 | 41.4995
Portland | Oregon | United States | -122.67621 | 45.52345
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Nashville | Tennessee | United States | -86.78444 | 36.16589
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Houston | Texas | United States | -95.36327 | 29.76328
Calgary | Alberta | Canada | -114.08529 | 51.05011
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Kingston | Ontario | Canada | -76.48098 | 44.22976
Kitchener | Ontario | Canada | -80.5112 | 43.42537
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Toronto | Ontario | Canada | -79.39864 | 43.70643
Greenfield Park | Quebec | Canada | -73.46223 | 45.48649
Lévis | Quebec | Canada | -71.17793 | 46.80326
| 0
|
NCT00073008
|
[
3
] | 45
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Study evaluating SOM230 in patients with metastatic carcinoid tumors
| null |
Carcinoid Tumors
|
SOM230 Sandostatin Carcinoid syndrome
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Open label. Patients received starting dose of 300 µg of study drug subcutaneously (s.c.) twice (total of 600 µg ) daily for three days, which could be increased in 150 µg increments up to 900 µg twice daily (total 1800 µg daily) if control of symptoms was not achieved. Prior sponsor agreement was required for a higher dose. A dose of 2400 µg/day was the maximum allowed. Dose reductions of 300 µg/day were allowed at any time if unacceptable toxicity occurred.
|
intervention 1: Pasireotide (SOM230)
| 4
|
Los Angeles | California | United States | -118.24368 | 34.05223
Tampa | Florida | United States | -82.45843 | 27.94752
Iowa City | Iowa | United States | -91.53017 | 41.66113
New Orleans | Louisiana | United States | -90.07507 | 29.95465
| 0
|
NCT00088595
|
[
4
] | 153
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This study is being conducted to compare the efficacy and safety of LAMICTAL (lamotrigine) extended-release with placebo in the treatment of Primary Generalized Tonic-Clonic (PGTC) seizures. LAMICTAL extended-release is an investigational drug. Placebo tablets look like LAMICTAL extended-release tablets but do not contain active medication. In this study, LAMICTAL extended-release or placebo tablets will be added to current seizure treatments.
| null |
Epilepsy, Tonic-Clonic
|
antiepileptic drugs seizures primary generalized tonic-clonic seizures Epilepsy lamotrigine anticonvulsants LAMICTAL
| null | 2
|
arm 1: None arm 2: None
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: Primary experimental dosage form intervention 2: Placebo control
|
intervention 1: lamotrigine (LAMICTAL) extended-release intervention 2: Placebo
| 146
|
Anniston | Alabama | United States | -85.83163 | 33.65983
Birmingham | Alabama | United States | -86.80249 | 33.52066
Northport | Alabama | United States | -87.57723 | 33.22901
Tuscaloosa | Alabama | United States | -87.56917 | 33.20984
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Newport Beach | California | United States | -117.92895 | 33.61891
Santa Monica | California | United States | -118.49138 | 34.01949
Sepuldeva | California | United States | N/A | N/A
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Hollywood | Florida | United States | -80.14949 | 26.0112
Maitland | Florida | United States | -81.36312 | 28.62778
Ocala | Florida | United States | -82.14009 | 29.1872
Atlanta | Georgia | United States | -84.38798 | 33.749
Augusta | Georgia | United States | -81.97484 | 33.47097
Marietta | Georgia | United States | -84.54993 | 33.9526
Savannah | Georgia | United States | -81.09983 | 32.08354
Suwanee | Georgia | United States | -84.0713 | 34.05149
Chicago | Illinois | United States | -87.65005 | 41.85003
Flossmoor | Illinois | United States | -87.68477 | 41.54281
Springfield | Illinois | United States | -89.64371 | 39.80172
Des Moines | Iowa | United States | -93.60911 | 41.60054
Wichita | Kansas | United States | -97.33754 | 37.69224
Crestview Hills | Kentucky | United States | -84.58494 | 39.02728
Louisville | Kentucky | United States | -85.75941 | 38.25424
Lafayette | Louisiana | United States | -92.01984 | 30.22409
Boston | Massachusetts | United States | -71.05977 | 42.35843
Detroit | Michigan | United States | -83.04575 | 42.33143
Grand Rapids | Michigan | United States | -85.66809 | 42.96336
Traverse City | Michigan | United States | -85.62063 | 44.76306
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Chesterfield | Missouri | United States | -90.57707 | 38.66311
Kansas City | Missouri | United States | -94.57857 | 39.09973
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Edison | New Jersey | United States | -74.4121 | 40.51872
West Orange | New Jersey | United States | -74.23904 | 40.79871
Amherst | New York | United States | -78.79976 | 42.97839
New York | New York | United States | -74.00597 | 40.71427
Asheville | North Carolina | United States | -82.55402 | 35.60095
Greenville | North Carolina | United States | -77.36635 | 35.61266
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Columbus | Ohio | United States | -82.99879 | 39.96118
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Germantown | Tennessee | United States | -89.81009 | 35.08676
Dallas | Texas | United States | -96.80667 | 32.78306
Galveston | Texas | United States | -94.7977 | 29.30135
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Wichita Falls | Texas | United States | -98.49339 | 33.91371
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Burlington | Vermont | United States | -73.21207 | 44.47588
Richmond | Virginia | United States | -77.46026 | 37.55376
Madison | Wisconsin | United States | -89.40123 | 43.07305
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Capital Federal | Buenos Aires | Argentina | N/A | N/A
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Curitiba | Paraná | Brazil | -49.27306 | -25.42778
Campinas | São Paulo | Brazil | -47.06083 | -22.90556
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
Santiago | Región Metro de Santiago | Chile | -70.64827 | -33.45694
Santiago | Región Metro de Santiago | Chile | -70.64827 | -33.45694
Singen | Baden-Wurttemberg | Germany | 8.8403 | 47.75935
Ulm | Baden-Wurttemberg | Germany | 9.99155 | 48.39841
Alzenau in Unterfranken | Bavaria | Germany | 9.06455 | 50.0888
Bamberg | Bavaria | Germany | 10.90067 | 49.89873
Fürth | Bavaria | Germany | 10.98856 | 49.47593
Munich | Bavaria | Germany | 11.57549 | 48.13743
Neuötting | Bavaria | Germany | 12.68998 | 48.24102
Straubing | Bavaria | Germany | 12.57385 | 48.88126
Unterhaching | Bavaria | Germany | 11.61564 | 48.06598
Würzburg | Bavaria | Germany | 9.95121 | 49.79391
Bernau bei Berlin | Brandenburg | Germany | 13.58708 | 52.67982
Ludwigsfelde | Brandenburg | Germany | 13.25405 | 52.30322
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Bad Homburg | Hesse | Germany | 8.61816 | 50.22683
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Bückeburg | Lower Saxony | Germany | 9.04939 | 52.26065
Göttingen | Lower Saxony | Germany | 9.93228 | 51.53443
Osnabrück | Lower Saxony | Germany | 8.0498 | 52.27264
Wismar | Mecklenburg-Vorpommern | Germany | 11.45563 | 53.89218
Wismar | Mecklenburg-Vorpommern | Germany | 11.45563 | 53.89218
Baesweiler | North Rhine-Westphalia | Germany | 6.18874 | 50.90964
Bochum | North Rhine-Westphalia | Germany | 7.21648 | 51.48165
Bochum | North Rhine-Westphalia | Germany | 7.21648 | 51.48165
Cologne | North Rhine-Westphalia | Germany | 6.95 | 50.93333
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Hattingen | North Rhine-Westphalia | Germany | 7.18557 | 51.39894
Mönchengladbach | North Rhine-Westphalia | Germany | 6.44172 | 51.18539
Münster | North Rhine-Westphalia | Germany | 7.62571 | 51.96236
Limburgerhof | Rhineland-Palatinate | Germany | 8.39194 | 49.42444
Flöha | Saxony | Germany | 13.07407 | 50.85613
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Bernburg | Saxony-Anhalt | Germany | 11.7401 | 51.79464
Halle | Saxony-Anhalt | Germany | 11.97947 | 51.48158
Köthen | Saxony-Anhalt | Germany | 11.97093 | 51.75185
Magdeburg | Saxony-Anhalt | Germany | 11.62916 | 52.12773
Magdeburg | Saxony-Anhalt | Germany | 11.62916 | 52.12773
Naumburg | Saxony-Anhalt | Germany | 11.80979 | 51.14987
Kiel | Schleswig-Holstein | Germany | 10.13489 | 54.32133
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Jena | Thuringia | Germany | 11.5899 | 50.92878
Hyderabad, Andhra Pradesh | N/A | India | 78.45636 | 17.38405
Lucknow | N/A | India | 80.92313 | 26.83928
New Delhi | N/A | India | 77.2148 | 28.62137
Kubang Kerian | N/A | Malaysia | 102.27938 | 6.09123
San Germán | Puerto Rico | Puerto Rico | -67.0449 | 18.08163
San Juan | Puerto Rico | Puerto Rico | -66.10572 | 18.46633
San Juan | Puerto Rico | Puerto Rico | -66.10572 | 18.46633
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Samara | N/A | Russia | 50.15 | 53.20007
St'Petersburg | N/A | Russia | N/A | N/A
Yekaterinburg | N/A | Russia | 60.6122 | 56.8519
Daejeon | N/A | South Korea | 127.38493 | 36.34913
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Kharkiv | N/A | Ukraine | 36.25475 | 49.98177
Kyiv | N/A | Ukraine | 30.5238 | 50.45466
Lviv | N/A | Ukraine | 24.02324 | 49.83826
| 0
|
NCT00104416
|
[
4
] | 337
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This 2 arm study will evaluate the efficacy, safety and tolerability of saquinavir/ritonavir or lopinavir/ritonavir in combination with emtricitabine/tenofovir in patients with human immunodeficiency virus type 1 (HIV-1) infection who have received no prior HIV treatment. Patients will be randomized to receive either saquinavir/ritonavir 1000/100mg oral (po) twice daily (bid) + emtricitabine/tenofovir 200/300mg po once daily (qd), or lopinavir/ritonavir 400/100mg po bid + emtricitabine/tenofovir 200/300mg po qd. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
| null |
HIV Infections
| null | 2
|
arm 1: saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks. arm 2: lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
|
[
0,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: 1000 milligram (mg) Oral (po) twice daily (bid) intervention 2: Lopinavir/ritonavir 400/100 mg po bid intervention 3: Emtricitabine/tenofovir disoproxil fumarate 200/300 mg po qd intervention 4: 100 mg po bid
|
intervention 1: saquinavir [Invirase] intervention 2: Lopinavir/ritonavir intervention 3: Emtricitabine/tenofovir disoproxil fumarate intervention 4: Ritonavir
| 44
|
Hobson City | Alabama | United States | -85.84413 | 33.62149
Tucson | Arizona | United States | -110.92648 | 32.22174
Berkeley | California | United States | -122.27275 | 37.87159
Los Angeles | California | United States | -118.24368 | 34.05223
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Jacksonville | Florida | United States | -81.65565 | 30.33218
Miami | Florida | United States | -80.19366 | 25.77427
Orlando | Florida | United States | -81.37924 | 28.53834
Vero Beach | Florida | United States | -80.39727 | 27.63864
Atlanta | Georgia | United States | -84.38798 | 33.749
Macon | Georgia | United States | -83.6324 | 32.84069
Chicago | Illinois | United States | -87.65005 | 41.85003
Ypsilanti | Michigan | United States | -83.61299 | 42.24115
St Louis | Missouri | United States | -90.19789 | 38.62727
Newark | New Jersey | United States | -74.17237 | 40.73566
New York | New York | United States | -74.00597 | 40.71427
Huntersville | North Carolina | United States | -80.84285 | 35.41069
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Houston | Texas | United States | -95.36327 | 29.76328
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Avignon | N/A | France | 4.80892 | 43.94834
Lyon | N/A | France | 4.84671 | 45.74846
Lyon | N/A | France | 4.84671 | 45.74846
Marseille | N/A | France | 5.38107 | 43.29695
Marseille | N/A | France | 5.38107 | 43.29695
Nantes | N/A | France | -1.55336 | 47.21725
Nice | N/A | France | 7.26608 | 43.70313
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Rouen | N/A | France | 1.09932 | 49.44313
Strasbourg | N/A | France | 7.74553 | 48.58392
Suresnes | N/A | France | 2.22929 | 48.87143
Toulouse | N/A | France | 1.44367 | 43.60426
Tourcoing | N/A | France | 3.16117 | 50.72391
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
Bangkok | N/A | Thailand | 100.50144 | 13.75398
| 0
|
NCT00105079
|
|
[
4
] | 230
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| true
|
This study will evaluate the efficacy and safety of administering an angiotensin converting enzyme inhibitor (ACE-I) (enalapril) to infants with a functional single ventricle. The study will also compare the effect of ACE-I therapy to placebo on somatic growth and compare the effect of ACE-I therapy to placebo on signs and symptoms of heart failure, neurodevelopmental and functional status, ventricular geometry, function, and atrioventricular (AV) valve regurgitation. In addition, the study will determine the relationship between genetic polymorphisms linked to ventricular hypertrophy (enlarged heart) and the response to ACE-I therapy and compare the incidence of adverse events in subjects treated with ACE-I with those in subjects treated with placebo.
|
BACKGROUND:
Growth impairment is common in infants and children with congenital heart disease, most often in the presence of congestive heart failure and/or cyanosis. Growth failure is noted in many infants with a single ventricle who manifest both cyanosis and heart failure that commonly persist after palliative surgery. Whether this impairment is related to persistent or progressive abnormalities in cardiac structure and function is not known. ACE-Is are widely used in the treatment of infants with severe congestive heart failure to improve cardiac function and somatic growth. The ability of an ACE-I to improve somatic growth in infants with a single ventricle has not been previously studied.
This study has been approved by the Institutional Review Boards/Research Ethics Boards of all participating clinical centers:
Hospital for Sick Children, Toronto, Canada
Children's Hospital Boston, Boston, MA
Columbia College of Physicians and Surgeons, New York, NY
Children's Hospital of Philadelphia, Philadelphia, PA
Duke University Medical Center, Durham, NC
Brody School of Medicine at East Carolina University, Greenville, NC
Wake Forest Baptist Medical Center, Winston Salem, NC
Medical University of South Carolina, Charleston, SC
Primary Children's Medical Center, Salt Lake City, UT
Children's Hospital of Wisconsin, Milwaukee, WI
Cincinnati Children's Hospital Medical Center, Cincinnati, OH
DESIGN NARRATIVE:
This is a prospective, randomized, double-blind, placebo-controlled trial of ACE-I in infants with a single ventricle. After stratification by ventricular anatomy, neonates will be randomly assigned to receive enalapril or placebo and then followed for 14 months.
|
Heart Defects, Congenital Heart Failure, Congestive
| null | 2
|
arm 1: Enalapril (angiotensin converting enzyme inhibitor) arm 2: Placebo (Ora-Plus and Ora-Sweet)
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Enalapril to target dose of .4mg/kg/day divided to twice per day (BID) intervention 2: Participants will receive placebo
|
intervention 1: Enalapril intervention 2: Placebo
| 9
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
New York | New York | United States | -74.00597 | 40.71427
Durham | North Carolina | United States | -78.89862 | 35.99403
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Charleston | South Carolina | United States | -79.93275 | 32.77632
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Toronto | Ontario | Canada | -79.39864 | 43.70643
| 0
|
NCT00113087
|
|
[
5
] | 302
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
This is a study involving treatment for alcohol dependence (alcoholism). The study will combine motivational enhancement therapy and cognitive behavioral therapy (combined behavioral intervention, or CBI) and tests the benefits of continued/discontinued treatment with naltrexone in a randomized placebo-controlled trial. CBI may have advantages in motivating patients to greater medication adherence and may address psychosocial factors that may limit the effects of naltrexone.
|
Naltrexone has been established as an efficacious medication to treat alcohol dependence but studies thus far have focused mostly on the acute phase of treatment rather than long-term management and have not offered alternative treatment strategies when patients do not respond to an initial course of naltrexone. For these initial non-responders to naltrexone, it is unclear what adjustments to treatment should be made to increase the likelihood of treatment success. We are unaware of previous research focused specifically on naltrexone non-response. Pilot data from ongoing trials at our center, however, suggest that up to a third of patients fail to respond to naltrexone. Moreover, these non-responsive patients go on to have the worst outcomes during the next 6 months of treatment if maintained on the same combination of naltrexone and medication management (MM). We propose to augment medication management with a combination of motivational enhancement therapy and cognitive behavioral therapy (combined behavioral intervention - CBI) and to test the benefits of continued/discontinued treatment with naltrexone in a randomized placebo-controlled trial. Clinical strategies for second line treatments often favor switching treatments rather than augmentation. However, there may be synergies between naltrexone and CBI that were not apparent with medication management. Specifically, CBI may have advantages in motivating patients to greater medication adherence (a leading cause of naltrexone treatment failure) and CBI may address psychosocial factors that limited or attenuated the effects of naltrexone.
|
Alcoholism
|
Alcoholism alcohol abuse therapy drug resistance naltrexone patient care management human subject
| null | 6
|
arm 1: From the start of baseline subjects were randomly assigned to this arm which defined relapse/non-responder as having 5 or heavy drinking days in the first 8 weeks of treatment otherwise the subject was considered a responder. arm 2: From the start of baseline subjects were randomly assigned to this arm which defined relapse/non-responder as having 2 or heavy drinking days in the first 8 weeks of treatment otherwise the subject was considered a responder. arm 3: Phase 2: Naltrexone and telephone counseling for responders. arm 4: Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR). arm 5: Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR) arm 6: Phase 2: Naltrexone and TAU for phase 1 responders.
|
[
0,
0,
0,
0,
2,
0
] | 5
|
[
0,
0,
5,
5,
5
] |
intervention 1: 100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2. intervention 2: placebo comparer for 16 weeks in phase 2. intervention 3: Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2. intervention 4: 45-60 minute sessions with a certified therapist focused on resolving ambivalence and skill building. Number of sessions guided by achievement of goals identified within treatment plan; minimum 9, maximum 20 sessions over 16 weeks. intervention 5: Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
|
intervention 1: Naltrexone intervention 2: placebo intervention 3: Medication Management (MM) intervention 4: Combined Behavioral Intervention (CBI) intervention 5: Telephone Counseling
| 1
|
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
| 0
|
NCT00115037
|
[
4
] | 523
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
This study determined the effectiveness of continuation phase cognitive therapy versus antidepressant medication in preventing relapse of depression in people with recurrent depression.
|
Cognitive therapy (CT) is a short-term talking therapy that focuses on changing negative thinking patterns and helping patients develop coping skills to deal with their experiences. Evidence suggests that CT is effective in treating a number of psychiatric conditions, including anxiety and anger. This study will determine the effectiveness of cognitive therapy versus antidepressant medication or placebo in preventing relapse of depression in people with recurrent depression.
This study lasted approximately 36 months and comprised three phases. For the first 12 weeks, all participants received between 16 and 20 CT sessions. Participants were then randomly assigned to receive additional CT sessions, antidepressants, or placebo for an additional 8 months. Upon completing treatment, participants entered follow-up study visits once every 4 months for the next 24 months. Clinician-rated scales and questionnaires were used to assess depressive symptoms of participants at study start and at the end of each study phase.
|
Depression
|
Cognitive therapy Antidepressants Psychotherapy
| null | 3
|
arm 1: Participants received acute phase and continuation phase cognitive therapy arm 2: Participants received acute phase cognitive therapy and continuation phase pill placebo arm 3: Participants received acute phase cognitive therapy and continuation phase fluoxetine
|
[
0,
2,
1
] | 4
|
[
5,
0,
10,
5
] |
intervention 1: Continuation phase cognitive therapy included 10 sessions over 8 months. intervention 2: The dosage of fluoxetine was increased to 40 mg over 8 months. intervention 3: The dosage of pill placebo was increased to 40 mg over 8 months. intervention 4: For the first 12 weeks, all participants received between 16 and 20 cognitive therapy sessions.
|
intervention 1: Continuation phase cognitive therapy intervention 2: Continuation phase fluoxetine intervention 3: Continuation phase pill placebo intervention 4: Acute phase cognitive therapy
| 2
|
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Dallas | Texas | United States | -96.80667 | 32.78306
| 0
|
NCT00118404
|
[
4
] | 137
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This study is intended to determine whether twice daily weight based dosing with recombinant human insulin-like growth factor (rhIGF-1) will safely and effectively increase the growth of prepubertal children with short stature associated with low IGF-1 levels but who produce sufficient growth hormone (GH). Subjects will be randomized to either an observation arm or to active treatment.
|
Prepubertal growth failure associated with primary IGF-1 deficiency (IGFD). Primary IGFD is a term that has been used to describe patients with intrinsic cellular defects in GH action. In this protocol, primary IGFD is defined as short stature (height standard deviation score\[SDS\]\<-2 below the mean for age and gender), low serum IGF-1 (IGF-1 SDS \<-2 below the mean for age and gender), and levels of growth hormone (GH) that are normal (≥7ng/mL) after a GH stimulation test. Primary IGFD is believed to result from a lower than normal ability to produce IGF-1 when exposed to normal levels of GH, i.e., a type of GH insensitivity or GH resistance.
This trial is one year, randomized, open label, observation-controlled, parallel-dose comparison efficacy and safety study conducted in approximately 40 centers across the United States.
|
Growth Disorders Insulin-Like Growth Factor-1 Deficiency
|
Primary IGF-1 Deficiency
| null | 4
|
arm 1: Observational Group arm 2: Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm. arm 3: Injection of rhIGF-1 80 μg/kg BID arm 4: Injection of rhIGF-1 120 μg/kg BID
|
[
4,
0,
0,
0
] | 1
|
[
0
] |
intervention 1: Twice Daily Injection
|
intervention 1: rhIGF-1 (mecasermin, Tercica, Inc.)
| 1
|
Brisbane | California | United States | -122.39997 | 37.68077
| 0
|
NCT00125164
|
[
3
] | 70
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for sickle cell anemia and sickle ß0-thalassemia. as evaluated by the number of occurrences of sickle cell crises.
|
The primary purpose of this study is to evaluate the effectiveness of oral L-glutamine in the therapy of sickle cell anemia and sickle ß0-thalassemia.
The secondary purpose is to assess the effect of L-glutamine frequency of hospitalizations for sickle cell pain, frequency of emergency room visits for sickle cell pain; energy and appetite levels; narcotics usage.
Methodology:
By site, patients will be randomized to L-glutamine or placebo in a 1:1 ratio after a 4-week screening period. Patients will undergo 48 weeks of treatment with dosing BID orally, with dose calculated according to patient weight. Patient visits will occur every 4 weeks. After 48 weeks of treatment, dose will be tapered to zero within 3 weeks. A final evaluation visit will occur 2 weeks after last dose.
|
Sickle Cell Anemia Thalassemia
|
sickle cell disease sickle cell anemia L-glutamine Sickle Cell Anemia (homozygous) Sickle ß0-Thalassemia
| null | 2
|
arm 1: L-glutamine arm 2: maltodextrin
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams. intervention 2: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
|
intervention 1: L-glutamine intervention 2: Placebo
| 5
|
Bellflower | California | United States | -118.11701 | 33.88168
Torrance | California | United States | -118.34063 | 33.83585
Atlanta | Georgia | United States | -84.38798 | 33.749
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
The Bronx | New York | United States | -73.86641 | 40.84985
| 0
|
NCT00125788
|
[
4
] | 114
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
The purpose of this study is to evaluate the safety and efficacy of everolimus in combination with basiliximab, and steroids with and without cyclosporine microemulsion in de novo kidney transplant recipients.
|
This is a combined analysis using 81 patients randomized and treated in CRAD001A2419 (NCT00154284) with 33 randomized and treated in CRAD001A2423 (NCT00170807). This approach is reflected in the protocol amendments for each study, and the one clinical study report for both.
|
Organ Transplantation, Renal Transplantation
|
Renal transplantation, everolimus, immunosuppressants, basiliximab, cyclosporine microemulsion discontinuation, cyclosporine microemulsion minimization
| null | 2
|
arm 1: Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice. arm 2: Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
|
[
1,
0
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: None intervention 2: None intervention 3: Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice. intervention 4: None
|
intervention 1: Everolimus (Certican) intervention 2: Cyclosporine (Neoral) intervention 3: Steroid intervention 4: Basiliximab (Simulect)
| 0
| null | 0
|
NCT00154284
|
[
2
] | 35
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to determine the dose limiting toxicities, minimum tolerated dose and recommended dose for Phase II studies.
| null |
Solid Malignancies
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Intravenous (IV) Infusion; 10, 20, 30, 35, 40 \& 45 mg/m2, once every 21 days (1 cycle), up to 9 cycles
|
intervention 1: Ixabepilone
| 3
|
Baltimore | Maryland | United States | -76.61219 | 39.29038
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
Cleveland | Ohio | United States | -81.69541 | 41.4995
| 0
|
NCT00162136
|
|
[
5
] | 45
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This is an open-label study with daily doses up to 144 mg/day Strattera (atomoxetine) in the treatment of adults with attention deficit hyperactivity disorder not otherwise specified. The researchers hypothesize ADHD symptomatology in adults with ADHD NOS will be responsive to Strattera treatment and Strattera treatment (in doses of up to 120 mg/day or 1.5 mg/kg/day, whichever is less) in adults with ADHD NOS will be safe and well tolerated.
|
Strattera (atomoxetine) is a non-stimulant specific norepinephrine reuptake inhibitor recently approved by the Food and Drug Administration for the treatment of child, adolescent and adult patients with ADHD. It is possible Strattera could be a viable alternative treatment for ADHD individuals. The purpose of this study is to assess the effectiveness, safety and tolerability of Strattera in adults with ADHD NOS. If this initial study shows promise, we will follow-up with a randomized clinical trial.
The study includes:
1. use of a six-week design to document the response rate,
2. weekly assessments to document the impact of Strattera NOS on functional capacities,
3. careful assessment of safety and tolerability.
Primary outcomes measure symptom reduction.
|
ADHD NOS
|
ADHD NOS Adults Strattera (atomoxetine) Open-Label
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Up to maximum of 1.2mg atomoxetine/kg PO QD, or 120 mg atomoxetine PO QD (whichever is less).
|
intervention 1: Strattera (atomoxetine)
| 1
|
Cambridge | Massachusetts | United States | -71.10561 | 42.3751
| 0
|
NCT00181766
|
[
3,
4
] | 49
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
African Americans receiving a kidney transplant are considered at high risk for early rejection of their transplanted kidney and require more immunosuppression to maintain their kidney transplant function. This increase in immunosuppression puts this group at risk for drug-related toxicities and complications such as post-transplant diabetes.
This study will evaluate:
1. Whether a sirolimus based steroid avoidance regimen in African Americans may decrease the risks of drug-related toxicities,
2. Decreased rates of metabolic complications such as post-transplant diabetes,
3. The effect of Sirolimus plus a reduced dose cyclosporine on renal allograft function.
|
This is an open labeled prospective trial with race matched historical controls. The treatment group (experimental arm) will be African American de novo solitary renal transplant recipients. The control arm will consist of race matched solitary renal transplant recipients who received a Cyclosporine (CsA) -based immunosuppressive regimen. The subjects will be matched for organ source (living donor vs. cadaveric). The experimental treatment arm will have an immunosuppression regimen consisting of Sirolimus, Reduced dose cyclosporine, Thymoglobulin, and only 3 doses of steroids.
|
End Stage Renal Disease Kidney Transplantation
| null | 1
|
arm 1: Thymoglobulin induction, sirolimus and no maintenance corticosteroid.
|
[
0
] | 1
|
[
0
] |
intervention 1: Thymoglobulin induction, sirolimus and no maintenance corticosteroid
|
intervention 1: Sirolimus
| 1
|
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
| 0
|
NCT00189202
|
|
[
5
] | 160
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This is an open-label, randomized, comparative, multicenter, 48-week study designed to evaluate the efficacy and safety of combination treatment with pegylated interferon and ribavirin in adult subjects with a diagnosis of compensated chronic hepatitis C (hepatitis C virus (HCV)-ribonucleic acid (RNA) positive) (Genotype 1). All subjects will complete 24 weeks of treatment, termed the Pilot Treatment Program, after which all eligible subjects will be randomly assigned to one of two study groups. One group will be followed for an additional 48 weeks without study medication, while the other will be continuously treated for an additional 24 weeks and then followed for another 24 weeks without study medication. Sustained virologic response, defined as undetectable HCV-RNA in serum at the end of the follow-up period, will be measured along with other outcomes.
|
This is an open-label, randomized, comparative, multicenter study for evaluation of PegIntron/Ribavirin therapy in the efficacy and safety in adult subjects with a diagnosis of compensated chronic hepatitis C (HCV-RNA+) (Genotype 1). This is a 48-week study, for which all subjects should participate in the Pilot Treatment Program and complete 24 weeks treatment. To avoid a treatment gap, subjects who will be screened and eligible subjects will sign informed consent prior to the end of the Pilot Treatment Program. After completion of the Pilot Treatment Program, all eligible subjects will be randomly assigned to either study group. Subjects in the 24-Week Treatment arm will be followed-up without study medication for 48 weeks; subjects in the 48-Week Treatment arm will be continuously treated for another 24 weeks and all subjects in the 48-Week Treatment arm will be followed for another 24 weeks after completion of the treatment period. Subjects in both arms will be evaluated at screening, randomization, 4, 8, 12, 16, 20, 24, 28, 36 and 48 weeks after randomization.
|
Hepatitis C, Chronic
| null | 2
|
arm 1: Genotype 1 hepatitis C virus \[HCV\] subjects treated for a total of 24 weeks, during the pilot treatment program (immediately before randomization) arm 2: Genotype 1 HCV subjects treated for a total of 48 weeks: 24 weeks during the pilot treatment program (immediately before randomization) plus 24 weeks during the extended treatment program (immediately after randomization)
|
[
0,
1
] | 4
|
[
2,
2,
0,
0
] |
intervention 1: Powder for injection in vial (120 microgram strength), subcutaneous, dose of 1.5 micrograms/kg weekly for 24 weeks during the pilot treatment program intervention 2: Powder for injection in vial (120 microgram strength), subcutaneous, dose of 1.5 micrograms/kg weekly for 24 weeks during the pilot treatment program followed by 1.2 to 1.5 microgram/kg weekly for 24 weeks during the extended treatment program intervention 3: 200 mg capsules, oral, weight-based dose of 1000 or 1200 mg, daily for for 24 weeks during the pilot treatment program intervention 4: 200 mg capsules, oral, weight-based dose of 1000 or 1200 mg, daily for for 24 weeks during the pilot treatment program and for 24 weeks during the extended treatment program
|
intervention 1: PegIntron (peginterferon alfa-2b; SCH 54031) intervention 2: PegIntron (peginterferon alfa-2b; SCH 54031) intervention 3: Ribavirin intervention 4: Ribavirin
| 0
| null | 0
|
NCT00202839
|
|
[
3
] | 27
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The study is designed to assess the efficacy of treatment with divalproex sodium (DS) vs. placebo in childhood/adolescent autism fulfilling DSM-IV and Autism Diagnostic Interview (ADI) criteria. Currently, there are no FDA-approved treatments for this disorder, although behavioral and educational therapies and a variety of medications may play a role in the management of some autistic symptoms.
|
This study compares divalproex sodium and placebo in the treatment of autistic disorder. Twenty six child or adolescent outpatients, with age ranges from 5-17, will be randomized into a 12-week double-blind, placebo-controlled parallel treatment study. During the 12 weeks, patients will be monitored by the treating psychiatrist and assessed by an independent evaluator (IE). The IE will perform study assessments while remaining blind to medication regimens (including possible tapering) as well as any side effects. Study assessments will be administered at designated time points
|
Autism
|
autism aggression irritability divalproex sodium
| null | 2
|
arm 1: Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium. arm 2: Subjects will receive the study drug, divalproex sodium.
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: Study drug. intervention 2: Placebo comparator.
|
intervention 1: Divalproex sodium intervention 2: Placebo
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00211757
|
[
5
] | 25
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The goals of this pilot study are as follows:
1\) To disseminate and examine the effectiveness of a manualized, individual, cognitive-behavioral psychotherapy (CBT) for adults with Generalized Anxiety Disorder(GAD), 2) to test the effectiveness of augmentation (the addition of) antidepressant therapy in participants who do not fully respond to CBT, and 3) to examine individual and clinical predictors of non-response to CBT and predictors of response to augmentation antidepressant therapy. A related goal is to examine the maintenance of treatment gains obtained from CBT alone and CBT with augmentation antidepressant therapy, over a twenty-four month follow-up period. This study will serve as a pilot investigation in preparation for a larger federally funded study using this treatment approach. We hypothesize that CBT will result in remission (no longer having GAD) and/or high endstate functioning (clinically meaningful improvement) in approximately 40-50% of participants. Further, we hypothesize that augmentation antidepressant therapy in participants who do not fully respond to CBT will result in further clinically significant improvement.
|
This pilot investigation will examine the effectiveness of augmenting cognitive behavioral therapy (CBT) with antidepressant pharmacotherapy (escitalopram\[Lexapro\]) in adults with generalized anxiety disorder (GAD) who do not fully respond to a temporally primary trial of CBT. A secondary aim of this study is to assess the maintenance of treatment gains made by patients in response to CBT, and to CBT with antidepressant augmentation therapy, over a two-year follow-up period.
CBT is an empirically supported psychotherapy that has been found to be effective in treating GAD in approximately 50 percent of patients enrolled in controlled clinical trials. However, a substantial proportion (nearly half) of individuals with GAD do not achieve full remission or clinically significant improvement at the cessation of CBT. Escitalopram (Lexapro)is a selective serotonin reuptake inhibitor (SSRI) antidepressant, which has been shown to be effective in treating GAD in several large-scale controlled clinical trials. The Food and Drug Administration has approved ecitalopram for the treatment of GAD.
The proposed research plan encompasses the conduct of an open clinical trial (No randomized placebo control) of 14 sessions of manualized individual CBT for persons meeting DSM-IV-TR diagnostic criteria for GAD. This study will use a treatment manual developed by Dr. Thomas Borkovec and colleagues at the Pennsylvania State University. Participants who meet high endstate functioning criteria and/or achieve remission following CBT will be evaluated periodically during a twenty-four month follow-up phase. Participants who do not meet high endstate functioning criteria and/or achieve remission following completion of CBT will be offered entry into a twelve-week, open-label, flexible-dose trial of escitalopram therapy. Participants receiving escitalopram therapy will be evaluated periodically during a twenty-four month follow-up phase, as well. It is anticipated that patients who do not fully respond to CBT will show a significant increment in improvement in GAD symptoms, over and above their CBT posttreatment level, following pharmacotherapy with escitalopram.
At present, no studies with GAD populations have examined the additive or sequenced effects of psychosocial therapy and SSRI antidepressant pharmacotherapy. The proposed research is a first step in this direction and may provide evidence supporting the use of combined treatment modalities in CBT partial and non-responders.
|
Generalized Anxiety Disorder
|
Anxiety Disorders Anxiety Neuroses Behavior Therapy, Cognitive Escitalopram
| null | 1
|
arm 1: 12 weeks of open label escitalopram, 10-20 mg/day (after 14 weeks of cognitive behavioral therapy
|
[
0
] | 2
|
[
5,
0
] |
intervention 1: 14 weekly sessions of individualized CBT intervention 2: 10-20 mg per day for 12 weeks
|
intervention 1: Cognitive Behavioral Therapy intervention 2: escitalopram
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00219349
|
[
3
] | 39
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This is a single institution Phase II study for patients with unresectable Stage IIIA and IIIB non-small cell lung cancer. The treatment started with 2 cycles of gemcitabine and carboplatin followed by concurrent chemotherapy with radiation. The chemoradiation included using paclitaxel and carboplatin with daily thoracic radiation to a total dose of 74 Gy. Response rate was determined following the chemotherapy with gemcitabine and carboplatin and evaluated again after the chemoradiation. Treatment toxicities were also assessed.
|
In this trial we adopted the approach of using both induction and concurrent chemotherapy together with Thoracic Radiation Therapy (TRT) planned conformally to a tumor dose of 74 Gy. Substitution of gemcitabine for paclitaxel in the induction chemotherapy allowed us to evaluate the impact of RRM1 expression on the activity of this agent. The expression of Ribonucleotide Reductase, M1 Subunit (RRM1) was evaluated prior to initiation of therapy, following induction chemotherapy but prior to concurrent chemoradiation, and following completion of all therapy by CT-guided core needle biopsies. This is a single institution phase II clinical trial, of induction treatment with gemcitabine and carboplatin followed by concurrent chemoradiation using paclitaxel and carboplatin and daily thoracic radiation to a total dose of 74 Gy for patients with unresectable Stage IIIA and IIIB NSCLC. The specific clinical objectives of this study are as follows: To determine the response rate (both CT scan and PET scan assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin; To determine the response rate (both CT scan and PET scan assessment) to concurrent thoracic radiation and weekly paclitaxel and carboplatin; To evaluate the patterns of local and distant failure for patients treated with induction chemotherapy followed by concurrent chemoradiation according to this regimen; To estimate the median, 1 year, and overall survival; To assess acute and long term toxicities of treatment.
|
Lung Cancer
|
non-small cell lung cancer carcinoma unresectable Stage IIIA Stage IIIB thoracic radiation
| null | 1
|
arm 1: In this trial we adopted the approach of using both induction and concurrent chemotherapy together with TRT planned conformally to a tumor dose of 74 Gy.
|
[
0
] | 4
|
[
0,
0,
0,
3
] |
intervention 1: Induction Chemotherapy. intervention 2: Induction Chemotherapy. Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy. intervention 3: Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy. intervention 4: Radiation Therapy will begin on day 57 if there has been adequate hematologic recovery from Induction Chemotherapy.
|
intervention 1: Gemcitabine intervention 2: Carboplatin intervention 3: Paclitaxel intervention 4: Radiation
| 1
|
Tampa | Florida | United States | -82.45843 | 27.94752
| 0
|
NCT00226590
|
[
0
] | 6
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The aim of this project is to evaluate the effects of the anticonvulsant drug lamotrigine (trade name Lamictal) on neuropathic facial pain or neuralgia using functional magnetic resonance imaging (fMRI).
|
Currently there are no pharmacological agents that can control neuropathic pain akin to the efficacy of antibiotics for bacterial infection. All current neuropathic pain drugs have approximately the same efficacy of less than 30% in controlled trials, and many of these drugs do not have known mechanisms of action. fMRI studies may provide insight into how brain circuitry is altered by chronic pain, and how these drugs act on altered circuitry. The trigeminal system in particular offers unique advantages for studying such alterations, including a large central representation and high degree of somatotopy. The administration of lamotrigine to neuropathic pain patients in conjunction with fMRI will allow us to compare subjective ratings of pain with objective measures of neural activity during increased conditions of allodynia/hyperalgesia.
|
Facial Neuropathy
|
pain neuropathic face trigeminal
| null | 2
|
arm 1: The drug lamotrigine will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout, placebo (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for placebo will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit. arm 2: The placebo will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout, the drug lamotrigine (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for drug will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit.
|
[
1,
1
] | 2
|
[
0,
0
] |
intervention 1: : 25mg and 50mg tablets intervention 2: Sugar pill manufactured to mimic Lamotrigine tablets
|
intervention 1: Lamotrigine intervention 2: Placebo (for Lamotrigine)
| 1
|
Belmont | Massachusetts | United States | -71.17867 | 42.39593
| 0
|
NCT00243152
|
[
3,
4
] | 27
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
The purpose of this study is to determine the effectiveness and tolerability of atomoxetine (Strattera) in adult patients with generalized social anxiety disorder (an anxiety disorder characterized by a fear of interpersonal interactions).
|
Controlled studies show that approximately 50% of patients with generalized social anxiety disorder(GSAD)will respond to treatment with available pharmacotherapeutic agents such as SSRI's. This still leaves 50% that respond partially or not at all. Those who do respond, often experience adverse events (e.g., sexual dysfunction), which leads them to discontinue treatment. Thus, there is a strong rational for identifying alternatives to SSRI's that are effective with fewer side effects (or with a different side-effect profile, that features less sexual dysfunction)for the treatment of GSAD. Available data demonstrate that sustained-release venlafaxine, a dual reuptake inhibitor, is also effective for GSAD.(Stein et al., 2005). It is unclear from these studies whether serotonin reuptake is integral to efficacy for social anxiety disorder, or whether norepinephrine reuptake will convey similar efficacy. Atomoxetine (Strattera)an inhibitor of the presynaptic norepinephrine transporter, is an ideal candidate to address both these issues.
|
Generalized Social Phobia
| null | 2
|
arm 1: Atomoxetine arm 2: Placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Flexible dose, up to 50 mg per day intervention 2: placebo (matching to atomoxetine)
|
intervention 1: atomoxetine intervention 2: placebo
| 0
| null | 0
|
NCT00260533
|
|
[
4
] | 664
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| true
| 0ALL
| false
|
The purpose of this study was to compare the safety and tolerability of the to-be-marketed lopinavir/ritonavir (LPV/r) tablet formulation with the marketed soft gel capsule (SGC) formulation and to compare the safety, tolerability, and antiviral activity of once daily (QD) and twice daily (BID) dosing of the LPV/r tablet formulation in combination with select nucleoside reverse transcriptase inhibitors (NRTIs) in patients who have not previously received antiretroviral treatment.
| null |
Human Immunodeficiency Virus Infections
|
Human Immunodeficiency Virus Infections
| null | 4
|
arm 1: None arm 2: None arm 3: None arm 4: None
|
[
0,
0,
1,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: LPV/r 800/200 mg once daily (QD) tablet + emtricitabine (FTC) 200 mg QD + tenofovir disoproxil fumarate (TDF) 300 mg QD intervention 2: LPV/r 800/200 mg QD soft gel capsule (SGC) + FTC 200 mg QD + TDF 300 mg QD (8 weeks) followed by LPV/r 800/200 mg QD Tablet + FTC 200 mg QD + TDF 300 mg QD intervention 3: LPV/r 400/100 mg twice daily (BID) tablet + FTC 200 mg QD + TDF 300 mg QD intervention 4: LPV/r 400/100 mg BID SGC + FTC 200 mg QD + TDF 300 mg QD (8 weeks) followed by LPV/r 400/100 mg BID Tablet + FTC 200 mg QD + TDF 300 mg QD
|
intervention 1: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs) intervention 2: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs) intervention 3: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs) intervention 4: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
| 129
|
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Beverly Hills | California | United States | -118.40036 | 34.07362
Fountain Valley | California | United States | -117.95367 | 33.70918
Long Beach | California | United States | -118.18923 | 33.76696
Newport Beach | California | United States | -117.92895 | 33.61891
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Atlantis | Florida | United States | -80.10088 | 26.5909
Fort Lauderdale | Florida | United States | -80.14338 | 26.12231
Miami | Florida | United States | -80.19366 | 25.77427
Orlando | Florida | United States | -81.37924 | 28.53834
Orlando | Florida | United States | -81.37924 | 28.53834
Plantation | Florida | United States | -80.23184 | 26.13421
Port Saint Lucie | Florida | United States | -80.35033 | 27.29393
Safety Harbor | Florida | United States | -82.69316 | 27.99085
Sarasota | Florida | United States | -82.53065 | 27.33643
Tampa | Florida | United States | -82.45843 | 27.94752
Atlanta | Georgia | United States | -84.38798 | 33.749
Macon | Georgia | United States | -83.6324 | 32.84069
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Wichita | Kansas | United States | -97.33754 | 37.69224
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
St Louis | Missouri | United States | -90.19789 | 38.62727
Rochester | New York | United States | -77.61556 | 43.15478
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
Hampton | Virginia | United States | -76.34522 | 37.02987
Darlinghurst | N/A | Australia | 151.21925 | -33.87939
Melbourne | N/A | Australia | 144.96332 | -37.814
South Yarra | N/A | Australia | 144.99149 | -37.83834
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Leuven | N/A | Belgium | 4.70093 | 50.87959
Liège | N/A | Belgium | 5.56749 | 50.63373
Calgary | N/A | Canada | -114.08529 | 51.05011
Hamilton | N/A | Canada | -79.84963 | 43.25011
Montreal | N/A | Canada | -73.58781 | 45.50884
Montreal | N/A | Canada | -73.58781 | 45.50884
Montreal | N/A | Canada | -73.58781 | 45.50884
Ottawa | N/A | Canada | -75.69812 | 45.41117
Ottawa | N/A | Canada | -75.69812 | 45.41117
Ste-Foy | N/A | Canada | N/A | N/A
Toronto | N/A | Canada | -79.39864 | 43.70643
Toronto | N/A | Canada | -79.39864 | 43.70643
Toronto | N/A | Canada | -79.39864 | 43.70643
Vancouver | N/A | Canada | -123.11934 | 49.24966
Vancouver | N/A | Canada | -123.11934 | 49.24966
Brno | N/A | Czechia | 16.60796 | 49.19522
Pilsen | N/A | Czechia | 13.37759 | 49.74747
Aix-en-Provence | N/A | France | 5.44973 | 43.5283
Besançon | N/A | France | 6.01815 | 47.24878
Lyon | N/A | France | 4.84671 | 45.74846
Montpellier | N/A | France | 3.87635 | 43.61093
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Rennes | N/A | France | -1.67429 | 48.11198
Vandœuvre-lès-Nancy | N/A | France | 6.17114 | 48.66115
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Bochum | N/A | Germany | 7.21648 | 51.48165
Bonn | N/A | Germany | 7.09549 | 50.73438
Cologne | N/A | Germany | 6.95 | 50.93333
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Fürth | N/A | Germany | 7.23919 | 49.42335
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hanover | N/A | Germany | 9.73322 | 52.37052
Athens | N/A | Greece | 23.72784 | 37.98376
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Brescia | N/A | Italy | 10.21472 | 45.53558
Florence | N/A | Italy | 11.24626 | 43.77925
Genoa | N/A | Italy | 8.94439 | 44.40478
Milan | N/A | Italy | 9.18951 | 45.46427
Milan | N/A | Italy | 9.18951 | 45.46427
Pavia | N/A | Italy | 9.15917 | 45.19205
Rome | N/A | Italy | 12.51133 | 41.89193
Rome | N/A | Italy | 12.51133 | 41.89193
Rome | N/A | Italy | 12.51133 | 41.89193
Turin | N/A | Italy | 7.68682 | 45.07049
Zwolle | N/A | Netherlands | 6.09444 | 52.5125
Chorzów | N/A | Poland | 18.9742 | 50.30582
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
San Juan | N/A | Puerto Rico | -66.10572 | 18.46633
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Singapore | N/A | Singapore | 103.85007 | 1.28967
A Coruña | N/A | Spain | -8.396 | 43.37135
Alicante | N/A | Spain | -0.48149 | 38.34517
Barakaldo | N/A | Spain | -2.98813 | 43.29639
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Santander | N/A | Spain | -3.80444 | 43.46472
Santiago de Compostela | N/A | Spain | -8.54569 | 42.88052
Seville | N/A | Spain | -5.97317 | 37.38283
Valencia | N/A | Spain | -0.37966 | 39.47391
Basel | N/A | Switzerland | 7.57327 | 47.55839
Geneva | N/A | Switzerland | 6.14569 | 46.20222
Lausanne | N/A | Switzerland | 6.63282 | 46.516
Sankt Gallen | N/A | Switzerland | 9.37477 | 47.42391
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Brighton | N/A | United Kingdom | -0.13947 | 50.82838
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
| 0
|
NCT00262522
|
[
5
] | 541
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The objective of the study is to compare the safety of innohep® and Unfractionated Heparin (UFH) in terms of clinically relevant bleedings in elderly patients with impaired renal function for initial treatment of acute Deep Venous Thrombosis (DVT).
The primary response criterion is the percentage of patients with clinically relevant bleeding events prior to day 90 +/- 5.
| null |
Deep Vein Thrombosis
|
Acute, symptomatic and objectively confirmed DVT
| null | 2
|
arm 1: innohep® 175 anti-Xa IU/kg once daily arm 2: Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: 175 anti-Xa IU/kg administered subcutaneously (SC) once daily intervention 2: Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily.
|
intervention 1: innohep® intervention 2: Heparin
| 9
|
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Zagreb | N/A | Croatia | 15.97798 | 45.81444
Prague | N/A | Czechia | 14.42076 | 50.08804
Brest | N/A | France | -4.48628 | 48.39029
Darmstadt | N/A | Germany | 8.65027 | 49.87167
Szczecin | N/A | Poland | 14.55302 | 53.42894
Bucharest | N/A | Romania | 26.10626 | 44.43225
Belgrade | N/A | Serbia | 20.46513 | 44.80401
Madrid | N/A | Spain | -3.70256 | 40.4165
| 0
|
NCT00277394
|
[
3
] | 98
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA).
Primary objective:
* To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA.
Secondary objective:
* To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population
* To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®).
This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation.
In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.
|
The study included :
* A screening phase up to 21 days followed by registration
* Treatment initiation within 5 working days of registration
* A treatment phase with 14-day study treatment cycles until a study withdrawal criterion was met or up to the clinical database cut-off date (18 July 2008)
* A follow-up phase - up to 60 days after end of treatment
Withdrawal criteria that led to treatment discontinuation were:
* The participant or their legally authorized representative requested to withdraw
* In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
* A specific request by the Sponsor
* Participant had intercurrent illness that prevented further administration of study treatment
* Participant had more than 2 aflibercept dose reductions
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
* Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
* Participant was lost to follow-up
After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.
|
Pulmonary Diseases Neoplasms, Lung
|
lung cancer non-small-cell lung cancer metastatic carcinoma lung neoplasm lung diseases angiogenesis anti-angiogenesis anti-angiogenesis inhibitors cancer and other neoplasms respiratory tract (lung and bronchial) diseases
| null | 1
|
arm 1: Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept every 2 weeks until a study withdrawal criterion was met.
|
[
0
] | 1
|
[
0
] |
intervention 1: Aflibercept 4.0 mg/kg administered intravenously (IV) over a period of at least 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level (to 3.0 mg/kg) or 2 dose levels (to 2.0 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
|
intervention 1: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
| 3
|
Bridgewater | New Jersey | United States | -74.64815 | 40.60079
Laval | N/A | Canada | -73.692 | 45.56995
Paris | N/A | France | 2.3488 | 48.85341
| 0
|
NCT00284141
|
[
3
] | 5
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The purpose of this study is to test the feasibility of using topiramate to reduce binge eating and drinking episodes in alcohol dependent individuals with comorbid binge eating disorder.
|
Research has shown an alarming coincidence of binge eaters also reporting serious alcohol abuse. Evidence has shown this population to have higher rates of psychiatric comorbidity, higher caloric intakes during meals, higher rates of tobacco use, more frequent binge episodes, and an earlier age of onset for binge eating and alcohol abuse. It is believed that topiramate may reduce binge eating and has been found helpful in reducing the cravings associated with alcohol consumption.
This study is to test the feasibility of administering topiramate to individuals with alcohol dependence and binge eating disorder. This will involve determining the adequacy of the amount of assessment and scheduled visits.
|
Alcohol Dependence Binge Eating
|
drinking eating obesity alcohol binge eating
| null | 1
|
arm 1: Drug: Topiramate Other Name for Topiramate: Topamax
|
[
0
] | 1
|
[
0
] |
intervention 1: Topiramate up to 300 mg per day.
|
intervention 1: Topiramate
| 2
|
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Richmond | Virginia | United States | -77.46026 | 37.55376
| 0
|
NCT00300742
|
[
4
] | 67
|
RANDOMIZED
|
FACTORIAL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this multi-center international trial is to evaluate the safety and effectiveness of adding iloprost or placebo (an inactive substance that contains no active study drug) to sildenafil therapy for pulmonary arterial hypertension (PAH). The study will also examine whether patients on sildenafil can reduce the number of iloprost inhalations from the approved 6 doses per day to 4 doses per day.
| null |
Pulmonary Hypertension
|
PAH Pulmonary Arterial Hypertension
| null | 5
|
arm 1: inhaled iloprost (5 μg) 6 times per day (6×/day) plus sildenafil with or without bosentan during the double blind period arm 2: Inhaled iloprost (5 μg) 4×/day plus inhaled placebo 2x/day plus sildenafil with or without bosentan during the double blind period arm 3: Inhaled placebo 6×/day plus sildenafil with or without bosentan during the double blind period arm 4: Inhaled iloprost (5 μg) 6 times per day (6×/day) plus sildenafil with or without bosentan during the Open-Label treatment period arm 5: Inhaled iloprost (5 μg) 4 times per day (4×/day) plus sildenafil with or without bosentan during the Open-Label treatment period
|
[
0,
0,
2,
0,
0
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: iloprost inhalation solution (Ventavis) (5 μg) intervention 2: inhaled placebo intervention 3: oral sildenafil (dosage between 60 and 300 mg/day) intervention 4: oral bosentan (dosage between 62.5 and 125 mg BID)
|
intervention 1: Inhaled Iloprost (5 μg) intervention 2: Inhaled Placebo intervention 3: Sildenafil intervention 4: Bosentan
| 0
| null | 0
|
NCT00302211
|
[
4
] | 155
|
RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
Trial 42603ATT3004 is an open-label extension study to clinical trial 42603ATT3002 (NCT00246220). In trial 42603ATT3002 the efficacy and safety of OROS methylphenidate was assessed in adult subjects with Attention Deficit Hyperactivity Disease (ADHD). ADHD is a developmental disorder beginning in childhood and characterized by developmentally inappropriate inattention, hyperactivity and impulsiveness. Data on the number of adult patients with ADHD is limited, but it is estimated that approximately 50% of children with ADHD will have symptoms also in adhulthood. The drug tested in this trial is OROS methylphenidate. The active ingredient is methylphenidate and the tablet is designed to release the active ingredient gradually to ensure an effect, which lasts up to 12 hours. Trial 42603ATT3002 consisted of a 5-week period, where subjects were assigned to either receive placebo (empty drug) or one out of three different dosages of OROS methylphenidate. This 5-week period was followed by a 7-week period, where patients received OROS methylphenidate at their optimal dose. In study 42603ATT3004, subjects who complete 42603ATT3002 are followed for a period of at least 52 weeks to evaluate safety and tolerability of OROS methylphenidate in patients who are treated with OROS methylphenidate over a long period of time.
Amendment: At the end of the open-label period of the present study 42603ATT3004, patients are enrolled into a double-blind placebo-controlled period, which lasts an additional 4 weeks. The purpose of this double-blind placebo-controlled period is to evaluate the maintenance of effect under continued treatment with OROS methlyphenidate in comparison to treatment cessation in those patients, who are randomized into the placebo-group.
|
This is an open label, multicentre extension study to trial 42603ATT3002. Patients, who were enrolled to trial 42603ATT3002 must have had a diagnosis of ADHD with some symptoms already present at the age of 7 and continuing in adulthood. The patients must have had at least mild to moderate symptoms of ADHD. In trial 42603ATT3002 the efficacy and safety of three fixed dosages of the study drug OROS methlyphenidate (MPH) was compared with placebo in adult subjects with ADHD in a double-blind phase. This double-blind phase was followed by an open-label phase, which was designed to assess the safety and tolerabiltiy of the study drug OROS methylphenidate in these subjects, when they got a dose, which was optimal to control their symptoms. In trial 42603ATT3004 patients are enrolled who completed the open-label phase of trial 42603ATT3002. Trial 42603ATT3004 is designed to assess the long-term safety and tolerabilty of OROS methylphenidate over a period of 52 weeks at a dose, which is optimal to control the symptoms. Patients may enter the extension study 42603ATT3004 at Visit 8 (End-of-Phase Visit, Open Label) of the 42603ATT3002 study as long as the patient has given informed consent prior to the visit being performed. Visit 8 data may then serve as baseline data for the extension study. These patients should continue treatment at the same optimal dosage of PR OROS methylphenidate as was attained during the open label phase of protocol 42603ATT3002. Patients who complete the 42603ATT3002 study, including post-study visit, may enter the extensions study up to 30 calendar days from the last dosing of open label trial medication of the 42603ATT3002 study. Patients should be titrated accordingly to their optimal dose attained in study 42603ATT3002. Patients will be assessed at regular intervals for at least 52 weeks.
Amendment: At completion of the open-label phase, patients can participate in a double-blind placebo-controlled phase, provided that they are giving written informed consent. At inclusion to the double-blind placebo-controlled phase, patients are assigned to one of two treatment arms by chance. One treatment arm will continue taking the same treatment at the same daily dose as during the open-label period. The other treatment arm will receive placebo treatment. As placebo, an inactive formulation or an empty treatment will be used. During the double-blind placebo-controlled phase, patients are asked to return to their doctor's office every other week. During these visits, physical examinations will be made, efficacy measures will be taken by means of questionnaires, that need to be completed either by the treating physician or the patient and any unwanted side effect will be recorded and treated if needed. One week after the end of the double-blind, placebo-controlled phase, patients have to return one more time to their doctor's office for the so called post-study visit, during which an additional physical examination will be performed and additional safety and efficacy parameters will be assessed.Patients will be assessed at regular intervals for at least 52 weeks. Daily oral dosages of 18, 36, 54, 72 and 90mg will be available and may be increased or decreased by 18mg increments based on clinical observations of response and tolerability for at least 52 weeks. Amendment: During the double-blind, placebo-controlled phase, patients will receive either active treatment at the previously assessed optimal dose or placebo tablets for a total of 4 weeks. Both treatments (active or placebo) are taken by mouth once per day in the morning.
|
Attention Deficit Disorder With Hyperactivity
|
Attention Deficit Hyperactivity Disorder Adult Long term safety Efficacy Quality of life
| null | 3
|
arm 1: open label PR OROS methylphenidate Flexible dosage MPH (18 to 90 mg/day) for 72 weeks (108 weeks for Germany) arm 2: double blind PR OROS methylphenidate 18 36 54 72 or 90 mg/day once daily for 4 weeks arm 3: double blind placebo matching placebo tablets once daily for 4 weeks
|
[
0,
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: matching placebo tablets once daily for 4 weeks intervention 2: 18, 36, 54,72 or 90 mg/day once daily for 4 weeks intervention 3: Flexible dosage MPH (18 to 90 mg/day) for 72 weeks (108 weeks for Germany)
|
intervention 1: double blind placebo intervention 2: double blind PR OROS methylphenidate intervention 3: open label PR OROS methylphenidate
| 21
|
Paris | N/A | France | 2.3488 | 48.85341
Ahrensburg | N/A | Germany | 10.22593 | 53.67515
Aschaffenburg | N/A | Germany | 9.15214 | 49.97704
Berlin | N/A | Germany | 13.41053 | 52.52437
Cologne | N/A | Germany | 6.95 | 50.93333
Essen | N/A | Germany | 7.01228 | 51.45657
Freiburg I. Br. | N/A | Germany | N/A | N/A
Homburg | N/A | Germany | 7.33867 | 49.32637
Mannheim | N/A | Germany | 8.46694 | 49.4891
Ottobrunn bei München | N/A | Germany | 11.66327 | 48.06489
Saarbrücken | N/A | Germany | 7.00982 | 49.23262
Würzburg | N/A | Germany | 9.95121 | 49.79391
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Drammen | N/A | Norway | 10.20449 | 59.74389
Ottestad | N/A | Norway | 11.1366 | 60.74743
Cascais | N/A | Portugal | -9.42147 | 38.69681
Porto | N/A | Portugal | -8.61099 | 41.14961
Barcelona | N/A | Spain | 2.15899 | 41.38879
Basel Bs | N/A | Switzerland | N/A | N/A
Zurich | N/A | Switzerland | 8.55 | 47.36667
| 0
|
NCT00307684
|
[
3
] | 961
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The purpose of this study is to determine whether treatment with esomeprazole for 6 months will improve asthma in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease.
| null |
Asthma GERD
|
Moderate to severe Asthma Gastroesophageal Reflux Disease esomeprazole GERD
| null | 3
|
arm 1: None arm 2: None arm 3: None
|
[
0,
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: Esomeprazole 40 mg twice daily intervention 2: Esomeprazole 40 mg once daily intervention 3: Placebo twice daily
|
intervention 1: Esomeprazole intervention 2: Esomeprazole intervention 3: Placebo
| 130
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Fountain Valley | California | United States | -117.95367 | 33.70918
Miami | Florida | United States | -80.19366 | 25.77427
Atlanta | Georgia | United States | -84.38798 | 33.749
Stockbridge | Georgia | United States | -84.23381 | 33.54428
Normal | Illinois | United States | -88.99063 | 40.5142
Overland Park | Kansas | United States | -94.67079 | 38.98223
Wichita | Kansas | United States | -97.33754 | 37.69224
Mandeville | Louisiana | United States | -90.06563 | 30.35825
Wheaton | Maryland | United States | -77.05526 | 39.03983
St Louis | Missouri | United States | -90.19789 | 38.62727
Papillion | Nebraska | United States | -96.04224 | 41.15444
Asheville | North Carolina | United States | -82.55402 | 35.60095
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Sylvania | Ohio | United States | -83.71299 | 41.71894
Medford | Oregon | United States | -122.87559 | 42.32652
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Upland | Pennsylvania | United States | -75.38269 | 39.85261
Charleston | South Carolina | United States | -79.93275 | 32.77632
Austin | Texas | United States | -97.74306 | 30.26715
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Kirkland | Washington | United States | -122.20874 | 47.68149
Seattle | Washington | United States | -122.33207 | 47.60621
Greenfield | Wisconsin | United States | -88.01259 | 42.9614
Ciudad de Buenos Aires | Argentina | Argentina | N/A | N/A
Monte Grande | Buenos Aires | Argentina | -58.46592 | -34.8194
Quilmes | Buenos Aires | Argentina | -58.25454 | -34.72065
Córdoba | Córdoba Province | Argentina | -64.18853 | -31.40648
Córdoba | Córdoba, Argentina | Argentina | -64.18853 | -31.40648
Rosario | Santa Fe Province | Argentina | -60.63932 | -32.94682
Rosario | Santa Fe, Argentina | Argentina | -60.63932 | -32.94682
San Miguel de Tucumán | Tucumán, Argentina | Argentina | -65.21051 | -26.81601
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Pleven | N/A | Bulgaria | 24.61667 | 43.41667
Plovdiv | N/A | Bulgaria | 24.75 | 42.15
Rousse | N/A | Bulgaria | 25.9534 | 43.84872
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Calgary | Alberta | Canada | -114.08529 | 51.05011
Bay Roberts | Newfoundland and Labrador | Canada | -53.26478 | 47.59989
Holyrood | Newfoundland and Labrador | Canada | -53.13137 | 47.38319
Brampton | Ontario | Canada | -79.76633 | 43.68341
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Toronto | Ontario | Canada | -79.39864 | 43.70643
Woodstock | Ontario | Canada | -80.7497 | 43.13339
La Malbaie | Quebec | Canada | -70.15268 | 47.654
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Benesov U Prahy | N/A | Czechia | N/A | N/A
Beroun | N/A | Czechia | 14.072 | 49.96382
Cvikov | N/A | Czechia | 14.63298 | 50.77668
Kladno | N/A | Czechia | 14.10285 | 50.14734
Kolín | N/A | Czechia | 15.1998 | 50.02806
Liberec | N/A | Czechia | 15.05619 | 50.76711
Prague | N/A | Czechia | 14.42076 | 50.08804
Rokycany | N/A | Czechia | 13.59459 | 49.7427
Tábor | N/A | Czechia | 14.6578 | 49.41441
Brest | N/A | France | -4.48628 | 48.39029
Férolles-Attilly | N/A | France | 2.63088 | 48.73184
Grasse | N/A | France | 6.92537 | 43.65783
Grenoble | N/A | France | 5.71479 | 45.17869
Marseille | N/A | France | 5.38107 | 43.29695
Montpellier | N/A | France | 3.87635 | 43.61093
Paris | N/A | France | 2.3488 | 48.85341
Saint-Laurent-du-Var | N/A | France | 7.19 | 43.67323
Villejuif | N/A | France | 2.35992 | 48.7939
Bad Wörishofen | N/A | Germany | 10.59666 | 48.00674
Berlin | N/A | Germany | 13.41053 | 52.52437
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Freising | N/A | Germany | 11.74876 | 48.40351
Gelnhausen | N/A | Germany | 9.18742 | 50.20164
Gelsenkirchen | N/A | Germany | 7.09654 | 51.50508
Hamburg | N/A | Germany | 9.99302 | 53.55073
Landsberg | N/A | Germany | 12.16076 | 51.52698
Marburg | N/A | Germany | 8.77069 | 50.80904
Nuremberg | N/A | Germany | 11.07752 | 49.45421
Potsdam | N/A | Germany | 13.06566 | 52.39886
Rodgau-dudenhofen | N/A | Germany | N/A | N/A
Wolmirstedt | N/A | Germany | 11.62945 | 52.24856
Budapest | N/A | Hungary | 19.04045 | 47.49835
Füzesabony | N/A | Hungary | 20.41667 | 47.75
Gyöngyös | N/A | Hungary | 19.928 | 47.78257
Győr | N/A | Hungary | 17.63512 | 47.68333
Hódmezővásárhely | N/A | Hungary | 20.33333 | 46.41667
Kaposvár | N/A | Hungary | 17.8 | 46.36667
Mosonmagyaróvár | N/A | Hungary | 17.26994 | 47.86789
Százhalombatta | N/A | Hungary | 18.93878 | 47.32949
Szombathely | N/A | Hungary | 16.62155 | 47.23088
Cagliari | CA | Italy | 9.11917 | 39.23054
Crema | CR | Italy | 9.68176 | 45.36264
Florence | FI | Italy | 11.24626 | 43.77925
Arenzano | GE | Italy | 8.68315 | 44.40521
Palermo | PA | Italy | 13.3636 | 38.1166
Pisa | PI | Italy | 10.4036 | 43.70853
Prato | PO | Italy | 11.09699 | 43.8805
Roma | Roma | Italy | 11.10642 | 44.99364
Bussolengo | VR | Italy | 10.85371 | 45.46903
Verona | VR | Italy | 10.9938 | 45.43854
Napoli | N/A | Italy | 14.5195 | 40.87618
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Zapopan | Jalisco | Mexico | -103.38742 | 20.72111
Morelia | Michoacán | Mexico | -101.18443 | 19.70078
Villahermosa | Tabasco | Mexico | -92.93928 | 17.98625
Mexico | N/A | Mexico | -98.43784 | 18.88011
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Gdynia | N/A | Poland | 18.53188 | 54.51889
Iława | N/A | Poland | 19.56849 | 53.59601
Krakow | N/A | Poland | 19.93658 | 50.06143
Lodz | N/A | Poland | 19.47395 | 51.77058
Piekary Śląskie | N/A | Poland | 18.92653 | 50.38017
Skarżysko-Kamienna | N/A | Poland | 20.87162 | 51.11311
Strzelce Opolskie | N/A | Poland | 18.30056 | 50.5107
Tarnów | N/A | Poland | 20.98698 | 50.01381
Zabrze | N/A | Poland | 18.78576 | 50.32492
Amadora | N/A | Portugal | -9.23083 | 38.75382
Covilha | N/A | Portugal | -7.50504 | 40.28106
Porto | N/A | Portugal | -8.61099 | 41.14961
Vila Nova de Gaia | N/A | Portugal | -8.61241 | 41.12401
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Nové Zámky | N/A | Slovakia | 18.16195 | 47.98544
Považská Bystrica | N/A | Slovakia | 18.42169 | 49.12153
Prievidza | N/A | Slovakia | 18.6275 | 48.77446
Rimavská Sobota | N/A | Slovakia | 20.02239 | 48.38284
Trenčín | N/A | Slovakia | 18.04436 | 48.89452
Basel | Canton of Basel-City | Switzerland | 7.57327 | 47.55839
| 0
|
NCT00317044
|
[
3
] | 15
|
NON_RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This phase II trial is studying how well sorafenib works in treating patients with soft tissue sarcoma. Sorafenib may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and blocking some of the enzymes needed for tumor cell growth
|
PRIMARY OBJECTIVES:
I. To determine if the combined vascular endothelial growth factor receptor 2 (VEGF-R2)/platelet-derived growth factor receptor (PDGFR)-beta inhibitor BAY 43-9006/ sorafenib can decrease interstitial fluid pressure (IFP) in soft tissue sarcomas.
II. To investigate the effects of BAY 43-9006/sorafenib on tumor blood flow, circulating endothelial cells, vascular density and pericyte coverage.
III. To characterize the pharmacokinetics of BAY 43-9006/sorafenib in sarcoma patients.
SECONDARY OBJECTIVES:
I. To describe any preliminary evidence of anti-tumor activity. II. Assess whether there are any significant relationships between systemic drug exposure and drug-related toxicity or biological effect.
OUTLINE: This is a multicenter study. Patients are assigned to one of two groups (group 1 closed to accrual as of 5/30/07).
GROUP I (SARCOMAS OF THE EXTREMITY) (CLOSED TO ACCRUAL AS OF 5/30/07): Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
GROUP II (METASTATIC OR INOPERABLE SARCOMAS): Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
In both groups, blood samples are drawn periodically for pharmacological studies.
After completion of study therapy, patients are followed monthly until all study-related toxicities are resolved and then at the discretion of the investigator.
|
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Metastatic Osteosarcoma Recurrent Adult Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Osteosarcoma Stage I Adult Soft Tissue Sarcoma Stage II Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma
| null | 2
|
arm 1: Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery. arm 2: Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
|
[
0,
0
] | 6
|
[
0,
3,
10,
10,
3,
3
] |
intervention 1: Given PO intervention 2: Undergo surgery intervention 3: Correlative studies intervention 4: Correlative studies intervention 5: Correlative studies intervention 6: Correlative studies
|
intervention 1: sorafenib tosylate intervention 2: therapeutic conventional surgery intervention 3: laboratory biomarker analysis intervention 4: pharmacological study intervention 5: computed tomography intervention 6: dynamic contrast-enhanced magnetic resonance imaging
| 1
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
| 0
|
NCT00330421
|
|
[
3
] | 18
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The purpose of this study is to explore benefits of duloxetine in enhancing psychological resilience and to understand the relevance of inhibiting of both serotonin (5HT) and norepinephrine (NE)to therapeutic responses.
|
This is an investigator-initiated, single-site study consisting of 8 weeks of open-label, fixed-dose treatment with duloxetine (30mg-60mg/day) in patients with Major Depressive Disorder (MDD).
|
Major Depressive Disorder
|
Depression Pharmacotherapy Duloxetine
| null | 1
|
arm 1: Open label treatment with Duloxetine for 8 weeks with dosing from 30-60 mg.
|
[
1
] | 1
|
[
0
] |
intervention 1: Open label treatment with Duloxetine for 8 wks. Dose 30-60 mg.
|
intervention 1: Duloxetine
| 1
|
Durham | North Carolina | United States | -78.89862 | 35.99403
| 0
|
NCT00331799
|
[
5
] | 54
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This study, conducted at the Phoenix Indian Medical Center, Phoenix, Arizona, will determine whether reducing subclinical inflammation lessens insulin resistance in healthy, obese volunteers. The study findings may lead to new strategies for preventing type 2 diabetes. In diabetes, blood sugar is higher than normal and can result in serious medical problems, such as blindness and kidney failure. People with subclinical inflammation-inflammation that does not produce symptoms, such as fever, pain, or skin redness-are at increased risk for diabetes. Although the reasons for this are not completely understood, it is known that subclinical inflammation exacerbates insulin resistance, which is a cause of diabetes. Insulin is a hormone that helps control blood sugar, and when it does not work properly, the condition is known as insulin resistance.
Normal, healthy volunteers between 18 and 45 years old with a body mass index of at least 30 kg/m2 and who have subclinical inflammation (determined by blood tests) may be eligible for this study. Candidates must be non-smokers and must not have an alcohol or drug problem. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Participants will maintain a standard diet and undergo tests and procedures during a 14-day inpatient stay at the Phoenix Indian Medical Center.
|
In healthy subjects, low-grade inflammation, as measured by serum levels of cytokines or acute phase proteins, is positively associated with adiposity. Recent studies indicate that chronic low-grade inflammation in non-diabetic individuals may cause decline in insulin sensitivity and increases the risk of developing type 2 diabetes. It has been proposed that reduction of low-grade inflammation may reduce the risk of development of type 2 diabetes. In agreement with this hypothesis, the class of anti-inflammatory drugs called salicylates (such as aspirin) that influence a specific anti-inflammatory pathway have been found to decrease plasma glucose levels and increase insulin sensitivity in rodents as well as people with type 2 diabetes.
In the present study, we propose testing whether administration of the anti-inflammatory drug Salsalate improves insulin sensitivity in obese non-diabetic individuals and whether this improvement is related with a decrease in serum markers of inflammation. Subjects will be randomly assigned to two treatment groups: placebo or Salsalate (3g/d). An oral glucose tolerance test and a combined euglycemic/hyperglycemic clamp to assess insulin sensitivity and insulin secretion will be performed before and after seven days of treatment. Results of this study may help to identify novel strategies to prevent type 2 diabetes in high-risk groups.
|
Type 2 Diabetes Diabetes
|
Salsalate Insulin Resistance Diabetes Mellitus Inflammation Diabetes HCV
| null | 2
|
arm 1: Salsalate (3g/day) for 7 days arm 2: Placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: The intervention was salsalate (3g/day) for 7 days. intervention 2: Identical placebo for 7 days.
|
intervention 1: Salsalate intervention 2: Placebo
| 1
|
Phoenix | Arizona | United States | -112.07404 | 33.44838
| 0
|
NCT00339833
|
[
5
] | 54
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction of FTC and Nevirapine. Truvada may be used.
|
Description of study design This is an open-labeled clinical trial evaluating an antiretroviral treatment regimen in which the drugs have demonstrated in vitro activity in both, resting and activated mononuclear cells. These drugs include: FTC 200 mg p.o. qd, and Tenofovir 300 mg p.o. qd, and Nevirapine 200 mg b.i.d.
Eligible patients must be at least 18 years of age, be referred by their primary HIV provider for antiretroviral therapy or if the patient is self referred, have a cluster of differentiation 4 (CD4) cell count of \< 250/mm3 and have a viral load \>5,000c/ml. Eligibility requirement for women is that they must have a CD4 cell count of \<250 at the time of enrollment. This cutoff for women is based on unpublished data that there may be increased hepatotoxicity in women with a CD4 cell count \> 250 cell/mm3. The screening evaluation will take place the day the informed consent is signed. During that screening evaluation, the patient will undergo a history and physical examination, and will have study labs drawn. Within 60 days of the screening evaluation and meeting all eligible criteria, the patient will be placed on the study treatment regimen. Patients will be evaluated at the clinic on Day 0 (therapy initiation), weeks 2, 4, 6, 8, 12, 16, and then every 8 weeks until 48 weeks and thereafter every 12 weeks through week 96. At the end of the study, all patients may continue their current antiretroviral treatment regimen at the discretion of the patient and their primary care provider.
Pharmacokinetic Analysis Sub Study A pharmacokinetic evaluation will be performed in first 7 volunteers to assess the impact of FTC on Nevirapine and vice versa. Pharmacokinetic analysis will be performed at end of week 2 ( day 14) during 200mg qd start up period. Samples will be obtained at baseline and 1, 3, 6, 12 and 24 hours post Nevirapine dosing. Pharmacokinetic analysis will be repeated at the week 8 visit. Samples will be obtained at baseline and 1, 3, 6, 12 and 24 hours post Nevirapine.
Assignment of patients There will be 60 patients involved in this clinical trial. This is an open-labeled study. There are no placebos involved in this study.
Dose and dose selection The dosages of medications are those that are currently used as standard clinical practice: Nevirapine 200 mg b.i.d. (1-200 mg tablet b.i.d.); Emtricitabine (FTC) 200mg po qd.(1-200mg capsule); Tenofovir 300 mg once-a-day (1-300 mg tablet qd).
Justification of study design All study patients require treatment for their HIV infection. All of the drugs used in this study are FDA-Approved. Tenofovir and FTC are approved as a once-a-day treatment medication. Nevirapine (NVP) is approved for BID dosing.
NOTE: That whenever Nevirapine is being prescribed, there will be a lead-in period of 14 days in which Nevirapine will be prescribed as 200 mg once a day followed by 200 mg BID as is the recommended standard of care.
|
HIV
| null | 1
|
arm 1: Open Label Drugs- Nevirapine 200 mg twice a day, FTC 200 mg once a day and Tenofovir 300 mg once a day for 96 weeks.
|
[
0
] | 1
|
[
0
] |
intervention 1: One arm only - Open label using FTC 200 mg p.o. qd, and Tenofovir 300 mg p.o. qd, and Nevirapine 200 mg b.i.d.
|
intervention 1: Nevirapine, FTC, and Tenofovir
| 1
|
Baltimore | Maryland | United States | -76.61219 | 39.29038
| 0
|
NCT00344461
|
|
[
4
] | 13
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this study is to compare the effectiveness of three different treatments for hepatic encephalopathy.
| null |
Hepatic Encephalopathy
|
Encephalopathy, Hepatic Portosystemic Encephalopathy Encephalopathy, Hepatocerebral Encephalopathy, Portal-Systemic Encephalopathy, Portosystemic Hepatic Coma Hepatic Stupor Hepatocerebral Encephalopathy Portal-Systemic Encephalopathy
| null | 3
|
arm 1: None arm 2: None arm 3: None
|
[
0,
0,
1
] | 3
|
[
0,
0,
10
] |
intervention 1: None intervention 2: None intervention 3: None
|
intervention 1: Rifaximin intervention 2: Lactulose intervention 3: Placebo
| 1
|
Miami | Florida | United States | -80.19366 | 25.77427
| 0
|
NCT00364689
|
[
4
] | 197
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The rationale for this Phase III study is to evaluate the 6 month safety and efficacy of eltrombopag in the treatment of previously treated subjects with chronic ITP. The starting dose of eltrombopag, 50 mg, once daily was selected based upon the observed efficacy, safety and pharmacokinetics in a dose-finding Study (TRA100773). This Phase III study is a randomized, double-blind, placebo-controlled, Phase III study, to evaluate efficacy, safety and tolerability of eltrombopag, initially administered as 50 mg oral tablets once daily for six months in adult subjects with previously treated chronic ITP. Subjects will be randomized 2:1, eltrombopag to placebo, and will be stratified based upon splenectomy status, use of ITP medication at baseline and baseline platelet count less than or equal to 15,000/µL. Subjects will receive study medication for 6 months, during which the dose of study medication may be adjusted based upon individual platelet counts. In addition, subjects may taper off concomitant ITP medications and may receive any rescue treatments as dictated by local standard of care. After discontinuation of study medication, subjects will complete follow-up visits at weeks 1, 2, 4 and months 3 and 6.
|
A randomized, double-blind, placebo-controlled phase III study, to evaluate the efficacy, safety and tolerability of eltrombopag olamine (SB-497115-GR), a thrombopoietin receptor agonist, administered for 6 months as oral tablets once daily in adult subjects with previously treated chronic idiopathic thrombocytopenic purpura (ITP).
|
Purpura, Thrombocytopaenic, Idiopathic
|
ITP idiopathic platelets purpura thrombocytopenia Idiopathic Thrombocytopenic Purpura thrombocytopenic
| null | 2
|
arm 1: Subjects will initiate treatment with 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down. arm 2: Subjects will initiate treatment with 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Subjects will initiate treatment with either 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down. intervention 2: Subjects will initiate treatment with either 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down
|
intervention 1: eltrombopag intervention 2: Placebo
| 115
|
Duarte | California | United States | -117.97729 | 34.13945
Los Angeles | California | United States | -118.24368 | 34.05223
San Francisco | California | United States | -122.41942 | 37.77493
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Hollywood | Florida | United States | -80.14949 | 26.0112
Atlanta | Georgia | United States | -84.38798 | 33.749
Savannah | Georgia | United States | -81.09983 | 32.08354
Honolulu | Hawaii | United States | -157.85833 | 21.30694
Boston | Massachusetts | United States | -71.05977 | 42.35843
Worcester | Massachusetts | United States | -71.80229 | 42.26259
St Louis | Missouri | United States | -90.19789 | 38.62727
Buffalo | New York | United States | -78.87837 | 42.88645
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Cleveland | Ohio | United States | -81.69541 | 41.4995
Lawton | Oklahoma | United States | -98.39033 | 34.60869
Portland | Oregon | United States | -122.67621 | 45.52345
Willow Grove | Pennsylvania | United States | -75.11573 | 40.144
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
Lubbock | Texas | United States | -101.85517 | 33.57786
Lubbock | Texas | United States | -101.85517 | 33.57786
Arlington | Virginia | United States | -77.10428 | 38.88101
Seattle | Washington | United States | -122.33207 | 47.60621
Tacoma | Washington | United States | -122.44429 | 47.25288
Vienna | N/A | Austria | 16.37208 | 48.20849
Burnaby | British Columbia | Canada | -122.95263 | 49.26636
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Weston | Ontario | Canada | -79.51513 | 43.70359
Greenfield Park | Quebec | Canada | -73.46223 | 45.48649
Laval | Quebec | Canada | -73.692 | 45.56995
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Jiang Su Province | N/A | China | N/A | N/A
Shanghai | N/A | China | 121.45806 | 31.22222
Tianjin | N/A | China | 117.17667 | 39.14222
Brno | N/A | Czechia | 16.60796 | 49.19522
Hradec Králové | N/A | Czechia | 15.83277 | 50.20923
Olomouc | N/A | Czechia | 17.25175 | 49.59552
Prague | N/A | Czechia | 14.42076 | 50.08804
Odense | N/A | Denmark | 10.38831 | 55.39594
Kuopio | N/A | Finland | 27.67703 | 62.89238
Bobigny | N/A | France | 2.45012 | 48.90982
Caen | N/A | France | -0.35912 | 49.18585
Créteil | N/A | France | 2.46569 | 48.79266
Pessac | N/A | France | -0.6324 | 44.80565
Munich | Bavaria | Germany | 11.57549 | 48.13743
Giessen | Hesse | Germany | 8.67554 | 50.58727
Hanover | Lower Saxony | Germany | 9.73322 | 52.37052
Saarbrücken | Saarland | Germany | 7.00982 | 49.23262
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Heraklion, Crete | N/A | Greece | 25.14341 | 35.32787
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Shatin | N/A | Hong Kong | 114.18333 | 22.38333
Bangalore | N/A | India | 77.59369 | 12.97194
Manipal | N/A | India | 74.78333 | 13.35
Napoli | Campania | Italy | 14.5195 | 40.87618
Bologna | Emilia-Romagna | Italy | 11.33875 | 44.49381
Albano Laziale (Roma) | Lazio | Italy | 12.659 | 41.72748
Milan | Lombardy | Italy | 9.18951 | 45.46427
Padua | Veneto | Italy | 11.88586 | 45.40797
Vicenza | Veneto | Italy | 11.5475 | 45.54672
Amersfoort | N/A | Netherlands | 5.3875 | 52.155
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Zwolle | N/A | Netherlands | 6.09444 | 52.5125
Auckland | N/A | New Zealand | 174.76349 | -36.84853
Auckland | N/A | New Zealand | 174.76349 | -36.84853
Christchurch | N/A | New Zealand | 172.63333 | -43.53333
Grafton | N/A | New Zealand | 174.76566 | -36.86029
Lima | Lima Province | Peru | -77.02824 | -12.04318
Lima | N/A | Peru | -77.02824 | -12.04318
Gdansk | N/A | Poland | 18.64912 | 54.35227
Krakow | N/A | Poland | 19.93658 | 50.06143
Legnica | N/A | Poland | 16.1619 | 51.21006
Opole | N/A | Poland | 17.92533 | 50.67211
Słupsk | N/A | Poland | 17.02872 | 54.46405
Torun | N/A | Poland | 18.59814 | 53.01375
Wroclaw | N/A | Poland | 17.03333 | 51.1
Moscow | N/A | Russia | 37.61556 | 55.75222
Novosibirsk | N/A | Russia | 82.94339 | 55.03442
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Košice | N/A | Slovakia | 21.25808 | 48.71395
Martin | N/A | Slovakia | 18.92399 | 49.06651
Prešov | N/A | Slovakia | 21.23393 | 48.99839
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Sfax | N/A | Tunisia | 10.76028 | 34.74056
Sousse | N/A | Tunisia | 10.63699 | 35.82539
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Dnipropetrovsk | N/A | Ukraine | 35.04066 | 48.46664
Kyiv | N/A | Ukraine | 30.5238 | 50.45466
Kyiv | N/A | Ukraine | 30.5238 | 50.45466
Lviv | N/A | Ukraine | 24.02324 | 49.83826
Odesa | N/A | Ukraine | 30.74383 | 46.48572
Plymouth | Devon | United Kingdom | -4.14305 | 50.37153
Taunton | Somerset | United Kingdom | -3.10293 | 51.01494
Leed | N/A | United Kingdom | N/A | N/A
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Morriston | N/A | United Kingdom | -3.92941 | 51.66995
Reading | N/A | United Kingdom | -0.97113 | 51.45625
Rhyl, Denbighshire | N/A | United Kingdom | -3.49228 | 53.31929
Ho Chi Minh City | N/A | Vietnam | 106.62965 | 10.82302
| 0
|
NCT00370331
|
[
4
] | 504
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 1FEMALE
| null |
The study will evaluate the efficacy and safety of transitioning postmenopausal women on current alendronate therapy to denosumab. Endpoints studied will include bone mineral density, bone turnover markers and bone histology in a subset of subjects.
| null |
Postmenopausal Osteoporosis
|
RANKL RANK denosumab AMG 162 osteoporosis bone turnover bone mineral density clinical trial postmenopausal osteoporosis alendronate total hip bone mineral density
| null | 2
|
arm 1: None arm 2: None
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: 70 mg oral QW intervention 2: 60 mg SC q 6 mos
|
intervention 1: alendronate intervention 2: Denosumab (AMG 162)
| 0
| null | 0
|
NCT00377819
|
[
2
] | 36
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This was a phase I dose escalation trial designed to determine the maximum tolerated dose (MTD) for the combination of romidepsin (depsipeptide) and gemcitabine. The study was originally planned as a Phase I/II; however only Phase I of the study was conducted.
| null |
Pancreatic Cancer
|
Pancreatic cancer advanced solid tumors
| null | 1
|
arm 1: Participants were to receive 7, 10 or 12 mg/m\^2 of romidepsin intravenously on either Days 1, 8 and 15 (Schedule A) or Days 1 and 15 (Schedule B) of each 28-day cycle, followed by 800 or 1000 mg/m\^2 of gemcitabine. Subsequent doses of both drugs were based on treatment-related toxicities. The planned duration of study therapy was 6 cycles or until disease progression occurred. Patients who responded could continue beyond 6 cycles until disease progression or until a withdrawal criterion was met.
|
[
0
] | 2
|
[
0,
0
] |
intervention 1: 7, 10 or 12 mg/m\^2 via intravenous infusion over 4 hours on either Days 1, 8 and 15 or Days 1 and 15 of each 28-day cycle. intervention 2: 800 or 1000 mg/m\^2 via intravenous infusion over 30 minutes on either Days 1,8 and 15 or Days 1 and 15 of each 28 day cycle.
|
intervention 1: Romidepsin intervention 2: Gemcitabine
| 1
|
Nashville | Tennessee | United States | -86.78444 | 36.16589
| 0
|
NCT00379639
|
[
5
] | 100
|
RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
This is a study of a medication, acamprosate, which is an FDA approved medication for alcohol problems. We will be examining whether acamprosate compared to a sugar pill (placebo) is more effective for helping with drinking in a Family Medicine clinic.
|
Acamprosate has been shown to reduce drinking days in alcohol dependent patients and promote abstinence, with few reported side effects. A limitation of these studies, however, has been their lack of generalizability due to restrictive inclusion and exclusion criteria. Furthermore, most of the previous studies of acamprosate have been conducted in Europe, in a different treatment setting from the typical American Family Medicine center, where alcohol dependent patients are most likely to be first identified in the U.S.
The present study is designed to determine the efficacy of acamprosatefor alcohol dependence in a Family Medicine setting using minimal psychotherapeutic interventions-as would also likely occur in a primary care setting. The study will be a 12-week, double-blind, placebo-controlled, randomized trial comparing 666 mg acamprosate t.i.d. to placebo in patients at the UNC Family Medicine Center with alcohol dependence. Subjects will be seen by Family Medicine physicians and receive brief motivational interventions. Primary efficacy will be determined by measuring % days abstinent and secondary outcomes include rates of complete abstinence, % heavy drinking days, CGI and GGT in the acamprosate group compared to the placebo group.
|
Alcohol Dependence
|
Alcohol Dependence Family Medicine Setting University of North Carolina at Chapel Hill
| null | 2
|
arm 1: The study is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive 333 mg t.i.d. oral acamprosate or matching placebo for a 12-week period. Each participant will also receive brief behavioral intervention at each visit. arm 2: The study is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive 333 mg t.i.d. oral acamprosate or matching placebo for a 12-week period. Each participant will also receive brief behavioral intervention at each visit.
|
[
1,
2
] | 1
|
[
0
] |
intervention 1: The study is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive 333 mg t.i.d. oral acamprosate or matching placebo for a 12-week period. Each participant will also receive brief behavioral intervention at each visit.
|
intervention 1: Acamprosate (Campral)
| 2
|
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
| 0
|
NCT00381043
|
[
3
] | 54
|
NA
|
SINGLE_GROUP
| 4SUPPORTIVE_CARE
| 0NONE
| false
| 0ALL
| true
|
RATIONALE: Aprepitant, palonosetron, and dexamethasone may help lessen or prevent nausea and vomiting in patients receiving chemotherapy.
PURPOSE: This phase II trial is studying how well giving aprepitant together with palonosetron and dexamethasone works in preventing nausea and vomiting caused by chemotherapy in patients receiving chemotherapy for metastatic colorectal cancer.
|
OBJECTIVES:
Primary
* Evaluate the efficacy, in terms of nausea and vomiting control, of aprepitant, palonosetron hydrochloride, and dexamethasone, in preventing chemotherapy-induced nausea and vomiting in patients receiving FOLFOX or FOLFIRI chemotherapy for metastatic colorectal cancer.
Secondary
* Assess the percentage of patients with no emesis and no rescue therapy when treated with aprepitant, palonosetron hydrochloride, and dexamethasone during repeated courses of FOLFOX or FOLFIRI chemotherapy.
* Assess the effects of aprepitant on nausea, appetite, taste changes (via visual analogue scale), nutritional intake, and mucositis in these patients.
* Assess the safety of this regimen in these patients.
OUTLINE: This is an open-label, multicenter study.
Beginning 1 hour prior to the initiation of chemotherapy on day 1, patients receive oral aprepitant on days 1-3, oral dexamethasone on days 1-4, and palonosetron hydrochloride IV on day 1.
Nausea is assessed daily for up to 4 courses of chemotherapy.
Quality of life is assessed at baseline.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
|
Colorectal Cancer Nausea and Vomiting
|
nausea and vomiting recurrent colon cancer stage IV colon cancer recurrent rectal cancer stage IV rectal cancer
| null | 1
|
arm 1: None
|
[
0
] | 8
|
[
0,
0,
0,
0,
0,
0,
0,
3
] |
intervention 1: Aprepitant 125 mg by mouth (PO) on day 1 and 80 mg PO on days 2 and 3 of each chemotherapy cycle intervention 2: Dexamethasone 12 mg PO on 1st day of study drug and 8 mg PO on days 2-4 intervention 3: as per institutional standard of care intervention 4: as per institutional standard of care intervention 5: as per institutional standard of care intervention 6: as per institutional standard of care intervention 7: Palonosetron 0.25 mg IV push on day 1 only. intervention 8: baseline
|
intervention 1: aprepitant intervention 2: dexamethasone intervention 3: fluorouracil intervention 4: irinotecan hydrochloride intervention 5: leucovorin calcium intervention 6: oxaliplatin intervention 7: palonosetron hydrochloride intervention 8: quality-of-life assessment
| 6
|
Savannah | Georgia | United States | -81.09983 | 32.08354
Hilo | Hawaii | United States | -155.09073 | 19.72991
Harvey | Illinois | United States | -87.64671 | 41.61003
Kansas City | Missouri | United States | -94.57857 | 39.09973
Portland | Oregon | United States | -122.67621 | 45.52345
Temple | Texas | United States | -97.34278 | 31.09823
| 0
|
NCT00381862
|
[
3
] | 60
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
Trial to determine the safety, efficacy and tolerability of acamprosate for the treatment of cocaine dependence.
|
The primary objective of the trial is to evaluate the safety, tolerability and efficacy of acamprosate for the treatment of 60 treatment seeking cocaine dependent outpatients. The study will be an exploratory, double-blind, placebo-controlled 9-week trial, with a 2-cell design (30 subjects per cell) in which either 1998 mg/day of acamprosate (666 mg TID) or placebo will be given. Study medications will be given by medical practitioners, trained to provide NIAAA's COMBINE Medical Management. In addition, patients will receive weekly individual psychosocial treatment sessions utilizing Cognitive Behavioral Therapy (CBT) at the University of Pennsylvania Treatment Research Center (TRC).
Primary Hypotheses:
1. Efficacy: Acamprosate-treated subjects will demonstrate less cocaine use during the medication/placebo treatment phase, compared to placebo-treated subjects. Cocaine use will be measured by self-report from the TLFB confirmed with urine assay for benzoylecgonine (BE)
2. Safety and Tolerability: Acamprosate-treated subjects and placebo-treated subjects will report similar rates of adverse events, assessed by weekly evaluations, physical exams and laboratory testing.
Secondary Hypotheses:
1. Acamprosate-treated subjects, compared to placebo-treated subjects, will report less craving for cocaine, measured by lower scores on the Brief Substance Craving Scale (BSCS) (Somoza et al, 1995) and Multiple Choice Procedure (MCP) (Griffiths et al., 1993) during the medication treatment phase.
2. Acamprosate-treated subjects, compared to placebo-treated subjects, will report fewer withdrawal symptoms, measured by the Cocaine Selective Severity Assessment (Kampman et al., 1998).
3. Acamprosate-treated subjects, compared to placebo-treated subjects, will report fewer mood and anxiety symptoms, measured by the Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1967), Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1969), and Clinical Global Impression Scale (CGI).
4. Subjects who are highly acamprosate-adherent (\>80% pills taken, verified by combining patient report with blister cards) will have more cocaine non-use days during the medication treatment phase, compared to those who are less acamprosate-adherent (\<80% pills taken).
|
Cocaine Dependence
|
cocaine
| null | 2
|
arm 1: 1998mg/day for 8 weeks arm 2: placebo pills for 8 weeks
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: 1998 mg/dau fpr 8 weeks intervention 2: placebo pills
|
intervention 1: acamprosate intervention 2: placebo
| 1
|
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
| 0
|
NCT00385268
|
[
4
] | 1,732
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.
| null |
Chronic Obstructive Pulmonary Disease
|
chronic obstructive pulmonary disease COPD indacaterol long-acting β2 agonist
| null | 4
|
arm 1: Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. arm 2: Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. arm 3: Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. arm 4: Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
[
0,
0,
1,
2
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI). intervention 2: Formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®). intervention 3: Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI). intervention 4: Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).
|
intervention 1: Indacaterol intervention 2: Formoterol intervention 3: Placebo to indacaterol intervention 4: Placebo to formoterol
| 183
|
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Mendoza | N/A | Argentina | -68.84582 | -32.88946
San Miguel | N/A | Argentina | -58.71229 | -34.54335
Santa Fe | N/A | Argentina | -60.70868 | -31.64881
Rancagua | N/A | Chile | -70.74053 | -34.1691
Santiago | N/A | Chile | -70.64827 | -33.45694
Viña del Mar | N/A | Chile | -71.55183 | -33.02457
Barranquilla | N/A | Colombia | -74.78132 | 10.96854
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Medellín | N/A | Colombia | -75.57151 | 6.245
Cvikov | N/A | Czechia | 14.63298 | 50.77668
Kyjov | N/A | Czechia | 17.12253 | 49.01018
Ostrava Poruba | N/A | Czechia | N/A | N/A
Pardubice | N/A | Czechia | 15.77659 | 50.04075
Prague | N/A | Czechia | 14.42076 | 50.08804
Tábor | N/A | Czechia | 14.6578 | 49.41441
Žatec | N/A | Czechia | 13.54577 | 50.32717
Aarhus | N/A | Denmark | 10.21076 | 56.15674
Copenhagen | N/A | Denmark | 12.56553 | 55.67594
Hellerup | N/A | Denmark | 12.57093 | 55.73204
Hvidovre | N/A | Denmark | 12.47708 | 55.64297
Molleparkvej | N/A | Denmark | N/A | N/A
Odense | N/A | Denmark | 10.38831 | 55.39594
Guayaquil | N/A | Ecuador | -79.88621 | -2.19616
Quito | N/A | Ecuador | -78.52495 | -0.22985
Quito | N/A | Ecuador | -78.52495 | -0.22985
Alexandria | N/A | Egypt | 29.91582 | 31.20176
Asyut | N/A | Egypt | 31.18368 | 27.18096
Cairo | N/A | Egypt | 31.24967 | 30.06263
Cairo | N/A | Egypt | 31.24967 | 30.06263
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Beuvry | N/A | France | 2.68541 | 50.51674
Chamalières | N/A | France | 3.06703 | 45.77364
Férolles-Attilly | N/A | France | 2.63088 | 48.73184
Grasse | N/A | France | 6.92537 | 43.65783
Marseille | N/A | France | 5.38107 | 43.29695
Montpellier | N/A | France | 3.87635 | 43.61093
Nice | N/A | France | 7.26608 | 43.70313
Nîmes | N/A | France | 4.35788 | 43.83665
Paris | N/A | France | 2.3488 | 48.85341
Perpignan | N/A | France | 2.89541 | 42.69764
Pessac | N/A | France | -0.6324 | 44.80565
Strasbourg | N/A | France | 7.74553 | 48.58392
Augsburg | N/A | Germany | 10.89851 | 48.37154
Bad Segeberg | N/A | Germany | 10.30745 | 53.93775
Bad Wörishofen | N/A | Germany | 10.59666 | 48.00674
Berlin | N/A | Germany | 13.41053 | 52.52437
Bielefeld | N/A | Germany | 8.53333 | 52.03333
Bochum | N/A | Germany | 7.21648 | 51.48165
Bonn | N/A | Germany | 7.09549 | 50.73438
Borstel | N/A | Germany | 8.96896 | 52.67034
Darmstadt | N/A | Germany | 8.65027 | 49.87167
Dortmund | N/A | Germany | 7.466 | 51.51494
Erfurt | N/A | Germany | 11.03283 | 50.9787
Forchheim | N/A | Germany | 11.05877 | 49.71754
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Gauting | N/A | Germany | 11.37703 | 48.06919
Geesthacht | N/A | Germany | 10.3779 | 53.43575
Gelsenkirchen | N/A | Germany | 7.09654 | 51.50508
Großhansdorf | N/A | Germany | 10.28333 | 53.66667
Gummersbach | N/A | Germany | 7.56473 | 51.02608
Hagen | N/A | Germany | 7.47168 | 51.36081
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hanover | N/A | Germany | 9.73322 | 52.37052
Ilvesheim | N/A | Germany | 8.5674 | 49.47404
Kassel | N/A | Germany | 9.5 | 51.31667
Kiel | N/A | Germany | 10.13489 | 54.32133
Leipzig | N/A | Germany | 12.37129 | 51.33962
Lübeck | N/A | Germany | 10.68729 | 53.86893
Lüdenscheid | N/A | Germany | 7.6273 | 51.21977
Mainz | N/A | Germany | 8.2791 | 49.98419
Marburg | N/A | Germany | 8.77069 | 50.80904
München | N/A | Germany | 13.31243 | 51.60698
Neumünster | N/A | Germany | 9.98456 | 54.07399
Nuremberg | N/A | Germany | 11.07752 | 49.45421
Oschersleben | N/A | Germany | 11.22898 | 52.03039
Rüdersdorf | N/A | Germany | 13.78631 | 52.46927
Schönefeld | N/A | Germany | 13.50374 | 52.38897
Strausberg | N/A | Germany | 13.88741 | 52.57859
Witten | N/A | Germany | 7.35258 | 51.44362
Wuppertal | N/A | Germany | 7.14816 | 51.25627
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Deszk | N/A | Hungary | 20.24322 | 46.21802
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Mosdós | N/A | Hungary | 17.98853 | 46.35379
Sopron | N/A | Hungary | 16.59049 | 47.68501
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Petah Tikva | N/A | Israel | 34.88747 | 32.08707
Rehovot | N/A | Israel | 34.81199 | 31.89421
Tel Litwinsky | N/A | Israel | 34.84588 | 32.05096
Ancona | N/A | Italy | 13.5103 | 43.60717
Catania | N/A | Italy | 15.07041 | 37.49223
Ferrara | N/A | Italy | 11.62057 | 44.83804
Florence | N/A | Italy | 11.24626 | 43.77925
Foggia | N/A | Italy | 15.55188 | 41.45845
Genova | N/A | Italy | 11.87211 | 45.21604
Milan | N/A | Italy | 12.59836 | 42.78235
Milan | N/A | Italy | 12.59836 | 42.78235
Pisa | N/A | Italy | 10.4036 | 43.70853
Roma | N/A | Italy | 11.10642 | 44.99364
Siena | N/A | Italy | 11.33064 | 43.31822
Daugavpils | N/A | Latvia | 26.53333 | 55.88333
Jēkabpils | N/A | Latvia | 25.85735 | 56.49903
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Alytus | N/A | Lithuania | 24.04142 | 54.39635
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Klaipėda | N/A | Lithuania | 21.13912 | 55.7068
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Almelo | N/A | Netherlands | 6.6625 | 52.35667
Amersfoort | N/A | Netherlands | 5.3875 | 52.155
Arnhem | N/A | Netherlands | 5.91111 | 51.98
Breda | N/A | Netherlands | 4.77596 | 51.58656
Ede | N/A | Netherlands | 5.65833 | 52.03333
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Harderwijk | N/A | Netherlands | 5.62083 | 52.34167
Helmond | N/A | Netherlands | 5.66111 | 51.48167
Hengelo | N/A | Netherlands | 6.79306 | 52.26583
Hoorn | N/A | Netherlands | 5.05972 | 52.6425
Leeuwarden | N/A | Netherlands | 5.80859 | 53.20139
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Sneek | N/A | Netherlands | 5.6589 | 53.03297
Veldhoven | N/A | Netherlands | 5.40278 | 51.41833
Zutphen | N/A | Netherlands | 6.20139 | 52.13833
Lima | N/A | Peru | -77.02824 | -12.04318
Lima | N/A | Peru | -77.02824 | -12.04318
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Iași | N/A | Romania | 27.6 | 47.16667
Timișoara | N/A | Romania | 21.22571 | 45.75372
Kazan' | N/A | Russia | 49.12214 | 55.78874
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Samara | N/A | Russia | 50.15 | 53.20007
Yekaterinburg | N/A | Russia | 60.6122 | 56.8519
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Partizánske | N/A | Slovakia | 18.38455 | 48.62861
Kyunggi | N/A | South Korea | N/A | N/A
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Suwon | N/A | South Korea | 127.00889 | 37.29111
Uijeongbu-si | N/A | South Korea | 127.0474 | 37.7415
Alicante | N/A | Spain | -0.48149 | 38.34517
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Begonte | N/A | Spain | -7.68643 | 43.15121
Cáceres | N/A | Spain | -6.37224 | 39.47649
Madrid | N/A | Spain | -3.70256 | 40.4165
Mataró | N/A | Spain | 2.4445 | 41.54211
Petrel | N/A | Spain | -0.77549 | 38.48289
Ponferrada | N/A | Spain | -6.59619 | 42.54664
Terrassa | N/A | Spain | 2.01667 | 41.56667
Valencia | N/A | Spain | -0.37966 | 39.47391
Aarau | N/A | Switzerland | 8.04422 | 47.39254
Basel | N/A | Switzerland | 7.57327 | 47.55839
Locarno | N/A | Switzerland | 8.79953 | 46.17086
Münchenstein | N/A | Switzerland | 7.60966 | 47.51848
Zurich | N/A | Switzerland | 8.55 | 47.36667
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Bursa | N/A | Turkey (Türkiye) | 29.06013 | 40.19559
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Mersin | N/A | Turkey (Türkiye) | 34.63886 | 36.81196
Yenişehir | N/A | Turkey (Türkiye) | 29.65306 | 40.26444
Belfast | N/A | United Kingdom | -5.92541 | 54.59682
Bexhill-on-Sea | N/A | United Kingdom | 0.47095 | 50.85023
Blackpool | N/A | United Kingdom | -3.05 | 53.81667
Chertsey | N/A | United Kingdom | -0.50782 | 51.38812
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Leicester | N/A | United Kingdom | -1.13169 | 52.6386
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Slough | N/A | United Kingdom | -0.59541 | 51.50949
Swansea | N/A | United Kingdom | -3.94323 | 51.62079
| 0
|
NCT00393458
|
[
3
] | 50
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
This is a study to evaluate the efficacy of the medication gabapentin in treating persons with cannabis dependence.
|
This is a 12-week, double blind, placebo controlled, dose ranging study to evaluate the efficacy of gabapentin in treating outpatients with cannabis dependence. Counseling and research assessments occur weekly throughout the 12-week treatment phase.
|
Cannabis Dependence
|
Cannabis treatment marijuana treatment
| null | 2
|
arm 1: 1200 mg/daily of Gabapentin arm 2: 1200mg/d of Placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Placebo intervention 2: None
|
intervention 1: Placebo intervention 2: Gabapentin
| 1
|
La Jolla | California | United States | -117.2742 | 32.84727
| 0
|
NCT00395044
|
[
3
] | 550
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
SMP-986 is a compound being developed for the treatment of overactive bladder syndrome (OABS). This clinical study is designed to test the hypothesis that SMP-986 at doses of 20mg, 40mg, 80mg or 120mg provides greater symptom relief in OABS compared to placebo. The hypothesis will be tested by measuring the change in mean voids/24 hrs after treatment with SMP-986 compared to placebo, as well comparing the change in: the severity of urgency episodes, mean number of urgency episodes/24 hr, mean number of incontinence episodes/24 hr and the mean void volume/void between SMP-986 and placebo.
|
A multicenter study conducted in patients with OABS comprising a 2-week single blind placebo run-in period followed by an 8-week randomized, double-blind, placebo controlled treatment period with patients randomized to receive 20 mg, 40 mg, 80 mg or 120 mg SMP 986 or placebo in a 1:1:1:1:1 ratio in parallel groups on an outpatient basis with study center visits.
|
Overactive Bladder Syndrome (OABS)
| null | 6
|
arm 1: Placebo run-in phase. 2 week duration. arm 2: To be taken for the 8 week duration, in parallel with alternative arms (doses of 20, 40, 80 or 120mg SMP-986). arm 3: 20mg dose of SMP-986 to be taken once daily for 8 week duration. arm 4: 40mg dose of SMP-986 to be taken for 8 week duration. arm 5: 80mg dose of SMP-986 to be taken for 8 week duration. arm 6: 120mg dose of SMP-986 to be taken for 8 week duration.
|
[
2,
2,
0,
0,
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Placebo, 2 week duration. intervention 2: Taken for the 8 week duration, in parallel with alternative arms (doses of 20, 40, 80 or 120mg SMP-986). intervention 3: Comparison of varying dosages (20, 40, 80 or 120mg) of SMP-986 against placebo. Dosing is to occur once daily, in the morning, for a duration of 8 weeks
|
intervention 1: Placebo intervention 2: Placebo intervention 3: SMP-986
| 69
|
Tuscon | Arizona | United States | N/A | N/A
Atherton | California | United States | -122.19774 | 37.46133
San Bernadino | California | United States | N/A | N/A
San Diego | California | United States | -117.16472 | 32.71571
Aventura | Florida | United States | -80.13921 | 25.95648
Boynton Beach | Florida | United States | -80.06643 | 26.52535
Ocala | Florida | United States | -82.14009 | 29.1872
Tallahassee | Florida | United States | -84.28073 | 30.43826
Alpharetta | Georgia | United States | -84.29409 | 34.07538
Kankakee | Illinois | United States | -87.86115 | 41.12003
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Garden City | New York | United States | -73.6343 | 40.72677
Kingston | New York | United States | -73.99736 | 41.92704
New York | New York | United States | -74.00597 | 40.71427
Poughkeepsie | New York | United States | -73.92097 | 41.70037
Hickory | North Carolina | United States | -81.3412 | 35.73319
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Richmond | Virginia | United States | -77.46026 | 37.55376
Spokane | Washington | United States | -117.42908 | 47.65966
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Toulouse | N/A | France | 1.44367 | 43.60426
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Buchholz | N/A | Germany | 9.56287 | 53.00884
Duisburg | N/A | Germany | 6.76516 | 51.43247
Düsseldorf | N/A | Germany | 6.77616 | 51.22172
Düsseldorf | N/A | Germany | 6.77616 | 51.22172
Hagenow | N/A | Germany | 11.19159 | 53.43134
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hamburg | N/A | Germany | 9.99302 | 53.55073
Leipzig | N/A | Germany | 12.37129 | 51.33962
Mannheim | N/A | Germany | 8.46694 | 49.4891
Markkleeberg | N/A | Germany | 12.36906 | 51.2755
München | N/A | Germany | 13.31243 | 51.60698
München | N/A | Germany | 13.31243 | 51.60698
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Gdansk | N/A | Poland | 18.64912 | 54.35227
Katowice | N/A | Poland | 19.02754 | 50.25841
Kutno | N/A | Poland | 19.36409 | 52.23064
Lodz | N/A | Poland | 19.47395 | 51.77058
Lodz | N/A | Poland | 19.47395 | 51.77058
Lublin | N/A | Poland | 22.56667 | 51.25
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Santa Cruz de Tenerife | Canary Islands | Spain | -16.25462 | 28.46824
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Madrid | N/A | Spain | -3.70256 | 40.4165
Aberdeen | N/A | United Kingdom | -2.09814 | 57.14369
Cambridge | N/A | United Kingdom | 0.11667 | 52.2
Crewe | N/A | United Kingdom | -2.44161 | 53.09787
London | N/A | United Kingdom | -0.12574 | 51.50853
Sheffield | N/A | United Kingdom | -1.4659 | 53.38297
| 0
|
NCT00409539
|
|
[
4
] | 25
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
The primary objective of this study is to evaluate the efficacy of 60mg of MCI-186 via intravenous drip once a day in patients with ALS whose severity is classified as grade III, based on the changes in the revised ALS functional rating scale (ALSFRS-R) scores after 24 weeks administration in double-blind, placebo-controlled manner. And in addition, this study will be performed to examine the safety of MCI-186 to ALS patients who met severity classification III.
| null |
Amyotrophic Lateral Sclerosis (ALS)
|
Amyotrophic lateral sclerosis free radical scavenger
| null | 2
|
arm 1: None arm 2: None
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Two ampoules (60 mg) of MCI-186 injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles). intervention 2: Two ampoules of Placebo injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).
|
intervention 1: MCI-186 intervention 2: Placebo of MCI-186
| 0
| null | 0
|
NCT00415519
|
[
4
] | 743
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The aim of the study is to compare the efficacy of roflumilast to placebo on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of tiotropium. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.
| null |
Chronic Obstructive Pulmonary Disease
|
COPD Roflumilast
| null | 2
|
arm 1: Roflumilast 500 µg
underlying medication: tiotropium 18 µg, once daily, inhaled arm 2: Placebo
underlying medication: tiotropium 18 µg, once daily, inhaled
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: 500 µg, once daily, oral administration in the morning intervention 2: once daily
|
intervention 1: Roflumilast intervention 2: Placebo
| 103
|
Feldbach | N/A | Austria | 15.88833 | 46.95306
Gänserndorf | N/A | Austria | 16.72016 | 48.33925
Hallein | N/A | Austria | 13.1 | 47.68333
Linz | N/A | Austria | 14.28611 | 48.30639
Spittal an der Drau | N/A | Austria | 13.5 | 46.8
Beuvry | N/A | France | 2.68541 | 50.51674
Chauny | N/A | France | 3.21857 | 49.61514
Grasse | N/A | France | 6.92537 | 43.65783
Lyon | N/A | France | 4.84671 | 45.74846
Martigues | N/A | France | 5.05526 | 43.40735
Montigny-lès-Metz | N/A | France | 6.15271 | 49.0956
Nantes | N/A | France | -1.55336 | 47.21725
Nice | N/A | France | 7.26608 | 43.70313
Nîmes | N/A | France | 4.35788 | 43.83665
Nîmes | N/A | France | 4.35788 | 43.83665
Ollioules | N/A | France | 5.84766 | 43.1399
Perpignan | N/A | France | 2.89541 | 42.69764
Saint-Laurent-du-Var | N/A | France | 7.19 | 43.67323
Saint-Quentin | N/A | France | 3.28757 | 49.84889
Toulon | N/A | France | 5.92836 | 43.12442
Bad Homburg | N/A | Germany | 8.61816 | 50.22683
Dortmund | N/A | Germany | 7.466 | 51.51494
Geesthacht | N/A | Germany | 10.3779 | 53.43575
Gelnhausen | N/A | Germany | 9.18742 | 50.20164
Göppingen | N/A | Germany | 9.65209 | 48.70354
Hanover | N/A | Germany | 9.73322 | 52.37052
Koblenz | N/A | Germany | 7.57883 | 50.35357
Landsberg/Lech | N/A | Germany | N/A | N/A
Leonberg | N/A | Germany | 9.01667 | 48.8
Marburg | N/A | Germany | 8.77069 | 50.80904
Saarbrücken | N/A | Germany | 7.00982 | 49.23262
Saarlouis | N/A | Germany | 6.75154 | 49.31366
Schwetzingen | N/A | Germany | 8.5823 | 49.38217
Sinsheim | N/A | Germany | 8.87867 | 49.2529
Weyhe | N/A | Germany | 8.66667 | 52.96667
Witten | N/A | Germany | 7.35258 | 51.44362
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Cegléd | N/A | Hungary | 19.79952 | 47.17266
Csorna | N/A | Hungary | 17.25012 | 47.61155
Érd | N/A | Hungary | 18.91361 | 47.39489
Győr | N/A | Hungary | 17.63512 | 47.68333
Hódmezovásárhely | N/A | Hungary | N/A | N/A
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Nyiregyháza | N/A | Hungary | N/A | N/A
Szentes | N/A | Hungary | 20.2608 | 46.65834
Szolnok | N/A | Hungary | 20.2 | 47.18333
Bassano Del Grappa (VI) | N/A | Italy | 11.72739 | 45.76656
Cisanello (PI) | N/A | Italy | N/A | N/A
Foggia | N/A | Italy | 15.55188 | 41.45845
Genova | N/A | Italy | 11.87211 | 45.21604
Milan | N/A | Italy | 12.59836 | 42.78235
Modena | N/A | Italy | 10.92539 | 44.64783
Pavullo Nel Frignano (MO) | N/A | Italy | 10.83544 | 44.33352
Pordenone | N/A | Italy | 12.66051 | 45.95689
Reggio Emilia | N/A | Italy | 10.63125 | 44.69825
Verona | N/A | Italy | 10.9938 | 45.43854
A Coruña | N/A | Spain | -8.396 | 43.37135
Alicante | N/A | Spain | -0.48149 | 38.34517
Baracaldo (Vizcaya) | N/A | Spain | -2.98813 | 43.29639
Candia | N/A | Spain | -7.5 | 43.35
Escaldes-Engordany | N/A | Spain | N/A | N/A
Galdakao | N/A | Spain | -2.8429 | 43.23073
Guadalajara | N/A | Spain | -3.16185 | 40.62862
Jerez de la Frontera | N/A | Spain | -6.13606 | 36.68645
Lleida | N/A | Spain | 0.62218 | 41.61674
Lugo | N/A | Spain | -7.55602 | 43.00992
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Mostoles Madrid | N/A | Spain | N/A | N/A
Pozuelo de Alarcón | N/A | Spain | -3.81338 | 40.43293
Requena | N/A | Spain | -1.10044 | 39.48834
Sant Cugat del Vallès | N/A | Spain | 2.08611 | 41.47063
Santa Cruz de Tenerife | N/A | Spain | -16.25462 | 28.46824
Seville | N/A | Spain | -5.97317 | 37.38283
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Ashford | N/A | United Kingdom | 0.87376 | 51.14648
Atherstone, Warwick | N/A | United Kingdom | N/A | N/A
Barry | N/A | United Kingdom | -3.2838 | 51.39979
Bexhill-on-Sea, East Sussex | N/A | United Kingdom | 0.47095 | 50.85023
Bolton | N/A | United Kingdom | -2.43333 | 53.58333
Bolton Lancs | N/A | United Kingdom | N/A | N/A
Chesterfield | N/A | United Kingdom | -1.41667 | 53.25
Chesterfield Derbyshire | N/A | United Kingdom | N/A | N/A
Chippenham | N/A | United Kingdom | -2.12472 | 51.46
Co. Antrim | N/A | United Kingdom | N/A | N/A
Darlington, Co. Durham | N/A | United Kingdom | -1.55039 | 54.52429
East Sussex | N/A | United Kingdom | N/A | N/A
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Harrow | N/A | United Kingdom | -0.33208 | 51.57835
Keresely End, Coventry | N/A | United Kingdom | -1.51217 | 52.40656
Plymouth | N/A | United Kingdom | -4.14305 | 50.37153
Sheffield | N/A | United Kingdom | -1.4659 | 53.38297
Solihull | N/A | United Kingdom | -1.78094 | 52.41426
Swindon, Wilts | N/A | United Kingdom | -1.78116 | 51.55797
Trowbridge | N/A | United Kingdom | -2.20861 | 51.31889
Watford | N/A | United Kingdom | -0.39602 | 51.65531
Yaxley | N/A | United Kingdom | -0.25852 | 52.51768
| 0
|
NCT00424268
|
[
3
] | 87
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
Safety and efficacy (measured by spirometry) of UK-432,097 administration will be tested in patients with chronic obstructive pulmonary disease.
| null |
Pulmonary Disease, Chronic Obstructive
|
Dry Powder for Inhalation Chronic Obstructive Pulmonary Disease Lung Function testing
| null | 2
|
arm 1: Active treatment given BID via a double pin monodose capsule inhaler device arm 2: Placebo treatment given BID via a single pin monodose inhaler device
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Formulated as a dry powder, supplied as capsules and administered using an atomizer device. Given as either 150mcg, 450mcg or 1350mcg BID. intervention 2: Capsules containing 100% lactose administered BID using an atomizer device
|
intervention 1: UK-432,097 intervention 2: Placebo
| 22
|
Camperdown | New South Wales | Australia | 151.17642 | -33.88965
Glebe | New South Wales | Australia | 151.18426 | -33.87884
Daw Park | South Australia | Australia | 138.58407 | -34.98975
Nedlands | Western Australia | Australia | 115.8073 | -31.98184
Calgary | Alberta | Canada | -114.08529 | 51.05011
Red Deer | Alberta | Canada | -113.802 | 52.26682
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Québec | Quebec | Canada | -71.21454 | 46.81228
Trois-Rivières | Quebec | Canada | -72.5477 | 46.34515
Almelo | N/A | Netherlands | 6.6625 | 52.35667
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Zuthpen | N/A | Netherlands | N/A | N/A
Bydgoszcz | Poland | Poland | 18.00762 | 53.1235
Gdansk | Poland | Poland | 18.64912 | 54.35227
Warsaw | Poland | Poland | 21.01178 | 52.22977
Lodz | N/A | Poland | 19.47395 | 51.77058
Chertsey | Surrey | United Kingdom | -0.50782 | 51.38812
Leicester | N/A | United Kingdom | -1.13169 | 52.6386
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Southampton | N/A | United Kingdom | -1.40428 | 50.90395
| 0
|
NCT00430300
|
[
5
] | 110
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 1FEMALE
| null |
This study will compare the effects of Zoledronic acid and Raloxifene in reducing bone turnover markers in postmenopausal women with low bone mineral density over 6 months.
| null |
Osteoporosis
|
Osteoporosis Post-menopausal Bone mineral density
| null | 2
|
arm 1: Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group) arm 2: Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
|
[
1,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: None intervention 2: None intervention 3: None intervention 4: None
|
intervention 1: Raloxifene intervention 2: Zoledronic acid intervention 3: Placebo oral pills intervention 4: Placebo intravenous (i.v.) infusion
| 17
|
Phoenix | Arizona | United States | -112.07404 | 33.44838
Buena Park | California | United States | -117.99812 | 33.86751
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Tampa | Florida | United States | -82.45843 | 27.94752
Springfield | Illinois | United States | -89.64371 | 39.80172
St Louis | Missouri | United States | -90.19789 | 38.62727
Omaha | Nebraska | United States | -95.94043 | 41.25626
Pahrump | Nevada | United States | -115.98391 | 36.20829
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
New York | New York | United States | -74.00597 | 40.71427
Burlington | North Carolina | United States | -79.4378 | 36.09569
Portland | Oregon | United States | -122.67621 | 45.52345
Portland | Oregon | United States | -122.67621 | 45.52345
Fort Worth | Texas | United States | -97.32085 | 32.72541
Renton | Washington | United States | -122.21707 | 47.48288
| 0
|
NCT00431444
|
[
5
] | 309
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This is a study designed to characterize the dermal response of DAYTRANA. Subjects will visit the study site over a period of approximately 14 weeks.
|
This is a study designed to characterize the dermal response of DAYTRANA. Subjects will visit the study site over a period of approximately 14 weeks. Subjects will be titrated to an optimum dose of study treatment and assessed for safety and efficacy. Dermal response will be evaluated at each visit by the investigator. Subjects with high dermal response scores or scores that persist at the same application site and have no improvement after up to 4 evaluations (not to exceed a two week period) will be discontinued from the study and referred to a study specific dermatologist for specialized skin sensitivity skin patch testing.
|
Attention Deficit Hyperactivity Disorder
| null | 1
|
arm 1: To characterize the dermal reactions seen with the use of DAYTRANA
|
[
0
] | 1
|
[
0
] |
intervention 1: Methylphenidate Transdermal System (MTS)
|
intervention 1: Daytrana
| 29
|
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Irvine | California | United States | -117.82311 | 33.66946
San Marcos | California | United States | -117.16614 | 33.14337
Spring Valley | California | United States | -116.99892 | 32.74477
Wildomar | California | United States | -117.28004 | 33.59891
Boulder | Colorado | United States | -105.27055 | 40.01499
Gainesville | Florida | United States | -82.32483 | 29.65163
Miami | Florida | United States | -80.19366 | 25.77427
Winter Park | Florida | United States | -81.33924 | 28.6
Libertyville | Illinois | United States | -87.95313 | 42.28308
Northbrook | Illinois | United States | -87.82895 | 42.12753
Overland Park | Kansas | United States | -94.67079 | 38.98223
Bardstown | Kentucky | United States | -85.4669 | 37.80923
Owensboro | Kentucky | United States | -87.11333 | 37.77422
Cambridge | Massachusetts | United States | -71.10561 | 42.3751
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Toms River | New Jersey | United States | -74.19792 | 39.95373
Rochester | New York | United States | -77.61556 | 43.15478
Cleveland | Ohio | United States | -81.69541 | 41.4995
Columbus | Ohio | United States | -82.99879 | 39.96118
Portland | Oregon | United States | -122.67621 | 45.52345
Salem | Oregon | United States | -123.0351 | 44.9429
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Jackson | Tennessee | United States | -88.81395 | 35.61452
Austin | Texas | United States | -97.74306 | 30.26715
Lubbock | Texas | United States | -101.85517 | 33.57786
San Antonio | Texas | United States | -98.49363 | 29.42412
Norfolk | Virginia | United States | -76.28522 | 36.84681
| 0
|
NCT00434213
|
|
[
3
] | 218
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 4QUADRUPLE
| false
| 0ALL
| false
|
The purpose of this study is to see how safe and effective Lacosamide (LCM) is when taken by mouth, twice a day for up to 18 weeks to prevent migraines.
|
This study is for subjects who have been diagnosed with migraine for at least one year and who are currently taking an effective abortive medication(s).
|
Migraine
|
Lacosamide migraine prophylaxis Vimpat
| null | 3
|
arm 1: Placebo arm 2: 100mg lacosamide arm 3: 300mg lacosamide
|
[
2,
0,
0
] | 3
|
[
0,
10,
0
] |
intervention 1: Lacosamide 100mg immediate-release film-coated tablet (white,oval) oral administration twice daily 12 hours apart intervention 2: Immediate-release film coated tablet (white, oval), oral administration twice daily 12 hours apart intervention 3: Lacosamide 300mg, immediate-release film coated tablet (white,oval), oral administration twice daily 12 hours apart.
|
intervention 1: Lacosamide intervention 2: Placebo intervention 3: Lacosamide
| 24
|
Huntsville | Alabama | United States | -86.58594 | 34.7304
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Walnut Creek | California | United States | -122.06496 | 37.90631
Boulder | Colorado | United States | -105.27055 | 40.01499
Palm Beach Gardens | Florida | United States | -80.13865 | 26.82339
South Miami | Florida | United States | -80.29338 | 25.7076
Sunrise | Florida | United States | -80.1131 | 26.13397
Conyers | Georgia | United States | -84.01769 | 33.66761
Evansville | Indiana | United States | -87.55585 | 37.97476
Wellesley Hills | Massachusetts | United States | -71.27867 | 42.30843
Worcester | Massachusetts | United States | -71.80229 | 42.26259
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Springfield | Missouri | United States | -93.29824 | 37.21533
St Louis | Missouri | United States | -90.19789 | 38.62727
Albany | New York | United States | -73.75623 | 42.65258
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Matthews | North Carolina | United States | -80.72368 | 35.11681
Cleveland | Ohio | United States | -81.69541 | 41.4995
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Nashville | Tennessee | United States | -86.78444 | 36.16589
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Alexandria | Virginia | United States | -77.04692 | 38.80484
Seattle | Washington | United States | -122.33207 | 47.60621
| 0
|
NCT00440518
|
[
3
] | 176
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| true
|
This study will evaluate the safety and efficacy of PF 03187207.
| null |
Primary Open Angle Glaucoma Ocular Hypertension Pigmentary Glaucoma Pseudoexfoliative Glaucoma
| null | 2
|
arm 1: One drop of each, once daily in study eye for 28 days arm 2: One drop of each, once daily in study eye for 28 days
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: None intervention 2: None
|
intervention 1: PF-03187207 and Latanoprost Vehicle intervention 2: Latanoprost 0.005% and PF-03187207 Vehicle
| 19
|
Artesia | California | United States | -118.08312 | 33.86585
Newport Beach | California | United States | -117.92895 | 33.61891
Petaluma | California | United States | -122.63665 | 38.23242
Poway | California | United States | -117.03586 | 32.96282
Danbury | Connecticut | United States | -73.45401 | 41.39482
Jacksonville | Florida | United States | -81.65565 | 30.33218
Ormond Beach | Florida | United States | -81.05589 | 29.28581
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Evansville | Indiana | United States | -87.55585 | 37.97476
Louisville | Kentucky | United States | -85.75941 | 38.25424
Rochester | New York | United States | -77.61556 | 43.15478
Charlotte | North Carolina | United States | -80.84313 | 35.22709
High Point | North Carolina | United States | -80.00532 | 35.95569
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Cranberry Township | Pennsylvania | United States | -80.10714 | 40.68496
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Memphis | Tennessee | United States | -90.04898 | 35.14953
Austin | Texas | United States | -97.74306 | 30.26715
| 0
|
NCT00441883
|
|
[
4
] | 140
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The purpose of this research study is to evaluate the safety and effectiveness of injection with DGE Injectable Gel (hyaluronic acid with lidocaine manufactured by Genzyme Biosurgery) as compared to injection with Restylane (a Food and Drug Administration (FDA) approved dermal filler) in patients undergoing cutaneous correction of the nasolabial folds (NLFs).
|
This study included an Initial and a Repeat Treatment period.
The Initial Treatment period was a subject and evaluator-blinded, randomized split face study in which subjects received DGE in one nasolabial fold and Restylane in the other nasolabial fold. Both safety and efficacy were evaluated.
In the Repeat Treatment Period, participants received DGE in both NLFs. Safety was evaluated.
|
Facial Wrinkles at the Nasolabial Folds
|
nasolabial folds facial wrinkles
| null | 2
|
arm 1: Participants received DGE in one nasolabial fold (NLF) of one side of their face (blinded, split-face study design) in the Initial Treatment period. Participants who continued into the Repeat Treatment period were treated with DGE as an open-label treatment. arm 2: Participants received Restylane in one nasolabial fold (NLF) of one side of their face (blinded, split-face study design) in the Initial Treatment period.
|
[
0,
1
] | 3
|
[
1,
1,
0
] |
intervention 1: Dermal Gel Extra (DGE) Injectable Gel contains hyaluronic acid with lidocaine. DGE was administered to nasolabial folds via the intradermal route. The Principal Investigator was instructed to inject a sufficient amount of DGE to ensure full correction of the NLF wrinkles (i.e., to the optimal level of correction achievable). Up to 2 touch-up treatments were allowed in the Initial Treatment period. intervention 2: Restylane was administered to nasolabial folds via the intradermal route. The Principal Investigator was instructed to inject a sufficient amount of Restylane to ensure full correction of the NLF wrinkles (i.e., to the optimal level of correction achievable). Up to 2 touch-up treatments were allowed in the Initial Treatment period. intervention 3: EMLA Cream (Eutectic Mixture of Local Anesthetics) is an FDA-approved topical anesthetic comprised of 2.5% each of lidocaine/prilocaine. EMLA Cream was applied in approximately equal amounts prior to all injections of DGE and Restylane.
|
intervention 1: Dermal Gel Extra (DGE) intervention 2: Restylane intervention 3: EMLA Cream
| 6
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
La Jolla | California | United States | -117.2742 | 32.84727
Miami Beach | Florida | United States | -80.13005 | 25.79065
Westwood | New Jersey | United States | -74.03264 | 40.99121
White Plains | New York | United States | -73.76291 | 41.03399
Nashville | Tennessee | United States | -86.78444 | 36.16589
| 0
|
NCT00444626
|
[
5
] | 244
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
This study will recruit 316 ischemic stroke patients taking aspirin.
They will be randomly assigned into cilostazol group or placebo group. Every patients will take 200mg of cilostazol a day or placebo for 1 month.
The primary outcome variable of this study is rate of biochemical aspirin resistance on the Ultra Rapid Platelet Function Assay-ASA.
|
\[Goal\] To reveal the effect and safety of additional cilostazol for overcoming biochemical aspirin resistance.
\[Trial Design\] Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial
\[Participants\] Ischemic stroke patients taking aspirin
\[Methods\]
* Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial
* Investigational product: Cilostazol 200mg (100mg twice per day)
* Concomitant medication: Aspirin 100 mg per day
* Medication Duration: 1 month
\[Outcome Variables\]
Primary Outcome Variable:
• the proportion of patients with aspirin reaction units (ARUs) values ≥550 on the Ultra Rapid Platelet Function Assay-ASA
Secondary outcome variables:
* the proportion of patients with ARUs values ≥500 on the Ultra Rapid Platelet Function Assay-ASA
* ARUs values
* Bleeding time (BT)
* Fatal or major bleeding complications
* Any bleeding complications
|
Cerebral Infarction
|
Infarction, Cerebral Cilostazol Aspirin Resistance
| null | 2
|
arm 1: 100mg of Cilostazol twice a day arm 2: matching placebo to cilostazol
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: cilostazol 100mg twice a day for 4 weeks intervention 2: placebo 1 tablet twice a day matching for cilostazol
|
intervention 1: Cilostazol intervention 2: placebo
| 4
|
Busan | Busan | South Korea | 129.03004 | 35.10168
Daejeon | N/A | South Korea | 127.38493 | 36.34913
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
| 0
|
NCT00446641
|
[
5
] | 331
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome (RLS) in comparison to placebo.
The key secondary objectives are to assess the effects on clinical global impressions - global improvement (CGI-I) (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (PGI) (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale (VAS)), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life Short Form 36 (SF-36) and on safety (based on adverse events (AE) profile) of pramipexole in comparison to placebo.
| null |
Restless Legs Syndrome
| null | 2
|
arm 1: 4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase or decrease the dose in steps to 0.25 mg, 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. arm 2: 4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: None intervention 2: None
|
intervention 1: Pramipexole intervention 2: Placebo
| 42
|
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Linz | N/A | Austria | 14.28611 | 48.30639
Edegem | N/A | Belgium | 4.44504 | 51.15662
Espoo | N/A | Finland | 24.6522 | 60.2052
Helsinki | N/A | Finland | 24.93545 | 60.16952
Joensuu | N/A | Finland | 29.76316 | 62.60118
Oulu | N/A | Finland | 25.46816 | 65.01236
Tampere | N/A | Finland | 23.78712 | 61.49911
Berlin | N/A | Germany | 13.41053 | 52.52437
Bochum | N/A | Germany | 7.21648 | 51.48165
Ellwangen | N/A | Germany | 10.13173 | 48.96164
Hellersdorf | N/A | Germany | 13.6088 | 52.53319
Herborn | N/A | Germany | 8.30369 | 50.68135
Leipzig | N/A | Germany | 12.37129 | 51.33962
Schwerin | N/A | Germany | 11.41316 | 53.62937
Steglitz | N/A | Germany | 13.332 | 52.45606
Würzburg | N/A | Germany | 9.95121 | 49.79391
Carrigtohill | N/A | Ireland | -8.26333 | 51.90833
Co. Kildare | N/A | Ireland | N/A | N/A
Co. Tipperary | N/A | Ireland | N/A | N/A
Bennebroek | N/A | Netherlands | 4.59861 | 52.32083
Hoogwoud | N/A | Netherlands | 4.93889 | 52.71583
Musselkanaal | N/A | Netherlands | 7.01528 | 52.9325
Oude Pekela | N/A | Netherlands | 7.00972 | 53.10417
Oude Pekela | N/A | Netherlands | 7.00972 | 53.10417
Rijswijk | N/A | Netherlands | 4.32501 | 52.03634
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Brezno | N/A | Slovakia | 19.63631 | 48.80431
Košice | N/A | Slovakia | 21.25808 | 48.71395
Martin | N/A | Slovakia | 18.92399 | 49.06651
Barcelona | N/A | Spain | 2.15899 | 41.38879
Granada | N/A | Spain | -3.60667 | 37.18817
Madrid | N/A | Spain | -3.70256 | 40.4165
San Sebastián | N/A | Spain | -5.9 | 43.56667
Valencia | N/A | Spain | -0.37966 | 39.47391
Chorley | N/A | United Kingdom | -2.61667 | 53.65
Edgbaston, Birmingham | N/A | United Kingdom | N/A | N/A
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Reading | N/A | United Kingdom | -0.97113 | 51.45625
Waterloo, Liverpool | N/A | United Kingdom | N/A | N/A
| 0
|
NCT00472199
|
|
[
0
] | 15
|
NON_RANDOMIZED
|
CROSSOVER
| null | 0NONE
| true
| 0ALL
| false
|
This study will determine whether the protease inhibitor lopinavir/ ritonavir (Kaletra (Trademark)), which is used to treat HIV disease, lowers blood levels of the lipid-regulating drug gemfibrozil (Lopid (Trademark)) in HIV-negative healthy volunteers. Many patients with HIV infection who take protease inhibitors have abnormally high lipids (cholesterol and triglycerides). Gemfibrozil, commonly used to treat high triglycerides, often is not effective in HIV-infected patients taking protease inhibitors, possibly because of an interaction between the two medicines that causes a lowering of gemfibrozil's levels in the blood. Results from this study will give researchers information on whether lopinavir/ ritonavir affects the blood levels of gemfibrozil.
Healthy, normal volunteers between 18 and 65 years old who test negative for HIV may be eligible for this study.
On study day 1, subjects have a blood sample drawn from a catheter inserted into a vein in the arm to determine pre-dosing blood levels of gemfibrozil. They then take a gemfibrozil tablet and are given breakfast 30 minutes after taking the drug. Blood samples are obtained through the catheter at 0, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after dosing to determine gemfibrozil levels at those intervals. At the end of 12 hours, the catheter is removed and the subject is discharged from the clinic. The next morning subjects return to the clinic for another blood sample, collected through a vein in the arm.
Subjects begin taking lopinavir/ ritonavir between 7 and 35 days after their first dose, depending on their schedule and the clinic schedule. On the fourteenth day of dosing subjects come to the clinic and are given a single dose of gemfibrozil, as on study day 1, and have breakfast 30 minutes later. Blood samples are collected to determine gemfibrozil levels just like on study days 1 and 2. An additional sample is collected for routine lab tests.
|
Hyperlipidemia continues to be a common problem in individuals with HIV, particularly those receiving HIV protease inhibitors (PIs) or the nucleoside reverse transcriptase inhibitor, stavudine. PI-treated patients have been noted to have increases in low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol compared to PI-treatment naive individuals. The prevalence of lipid abnormalities in patients receiving PI-containing therapy has been estimated at 27-57 percent; moreover, cardiovascular complications have begun to be revealed. Triglyceride elevations, in particular, are not only an independent risk factor for the development of coronary artery disease, but may also lead to pancreatitis. Despite treatment with fibric acid derivatives, such as gemfibrozil, TGs typically remain elevated above the upper limit of normal in HIV-infected subjects. One possible reason for persistently elevated TGs in these patients is reduced efficacy of their fibric acid therapy, which may result from an unrecognized drug-drug interaction. Fibric acid derivatives are metabolized in the liver via uridine 5'-diphosphate-glucuronosyl transferase enzymes (UGT), which are induced by the HIV PI ritonavir. Indeed, ritonavir significantly lowers plasma concentrations of other drugs metabolized by this enzymatic system by 40-50 percent. As UGT activity is induced, the metabolism of UGT substrates (gemfibrozil) will increase, resulting in a decrease in their plasma concentrations. Preliminary data in non-HIV-infected subjects suggest that reduced plasma concentrations of gemfibrozil are likely to result in reduced efficacy of the drug. Despite the fact that many HIV-infected patients with hypertriglyceridemia are likely to be receiving triglyceride-lowering therapy with a fibric acid derivative while simultaneously receiving antiretroviral therapy that includes ritonavir (i.e. lopinavir + ritonavir \[LPV/r\]), these two drugs have not been studied in combination to determine whether or not they interact. The objective of this study is to characterize the impact of LPV/r on the pharmacokinetic (PK) profile of gemfibrozil, after a single 600 mg oral dose, administered to healthy volunteers. In a longitudinal study design, fifteen subjects will receive a single, 600 mg dose of gemfibrozil before and after 13 days of LPV/r 400/100 mg twice daily. Gemfibrozil pharmacokinetics will be determined on days one and 14 and compared using the student t-test. Results from this study will provide (or refute) the rationale for further studies designed to assess the possibility of dose-adjusting gemfibrozil when it is given in combination with ritonavir in order to maximize the pharmacologic effects of gemfibrozil.
|
Healthy Volunteers
|
Pharmacokinetic HIV Drug-Drug Interaction Lopinavir/Ritonavir Gemfibrozil Healthy Volunteer HV
| null | 2
|
arm 1: Subjects received a single 600 mg dose of gemfibrozil without concurrent lopinavir-ritonavir 400mg/100mg; this is the "control" arm of a crossover study design. arm 2: Single dose (600 mg) Gemfibrozil pharmacokinetics (i.e. plasma concentrations collected over time to calculate area under the concentration vs. time curve) assessed after 14.5 days of lopinavir/ritonavir (400/100 mg twice daily) administration.
|
[
3,
0
] | 2
|
[
0,
0
] |
intervention 1: lopinavir 400 mg + ritonavir 100 mg twice daily for 2 weeks intervention 2: Control arm (no intervention used in this arm)
|
intervention 1: Lopinavir/Ritonavir intervention 2: Gemfibrozil
| 1
|
Bethesda | Maryland | United States | -77.10026 | 38.98067
| 0
|
NCT00474201
|
[
4
] | 990
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The purpose of this study is to evaluate whether tapentadol (CG5503) prolonged-release (PR) tablets at doses of 100-250 mg twice daily provide a better pain relief in patients with moderate to severe chronic pain due to osteoarthritis of the knee than a placebo (a medication without active substance). In addition the tolerability of CG5503 PR will be assessed. One third of the patients will receive CG5503 and one third will receive placebo. For further comparison one third of the patients will receive oxycodone controlled release (CR) at doses of 20-50 mg twice daily which is an active approved pain medication. Please note that tapentadol ER (Extended Release) and tapentadol PR (Prolonged Release) are identical and used interchangeably. This is due to United States of America and European naming conventions.
|
This is a randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows which patient gets which study medication, i.e. CG5503, placebo, oxycodone), placebo and active control study. The primary objective is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) prolonged-release (PR) at doses of 100-250 mg (base) twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study will consist of five periods: screening (to assess eligibility), washout (3-7 days with determination of a baseline pain intensity), titration (of dose over 3 weeks to the optimal individual level), maintenance (investigational drug intake for 12 weeks with adjustments allowed), and follow-up (2 weeks after end of treatment). The study hypothesis is that the study drug will be more effective than placebo in reducing patients' pain intensity. The secondary objectives include the collection of pharmacokinetic (related to how the body absorbs, distributes, changes and excretes the drug) information for dose verification. The efficacy objectives will be assessed by comparing the baseline pain level to the pain level during the maintenance period. This will be done by looking at the patients' pain diary information (electronic diaries).
|
Pain Knee Osteoarthritis
|
Osteoarthritis Knee Pain Assessment CG5503 PR Centrally acting analgesic Placebo Oxycodone Chronic Pain due to knee Osteoarthritis Tapentadol
| null | 3
|
arm 1: The starting dose of placebo was matched with the active treatment arms taken twice daily for the first 3 days. The dose was then increased to match the active treatments for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days as in the active treatment arms. Dose decreases were allowed without time restrictions. arm 2: The starting dose was tapentadol ER 50 mg twice daily for 3 days. The dose was then increased to 100 mg tapentadol ER twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions. arm 3: The starting dose was oxycodone CR 10 mg twice daily for 3 days. The dose was then increased to 20 mg oxycodone CR twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions.
|
[
2,
0,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: 50, 100, 150, 200, 250 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance) intervention 2: Matching Placebo during 15 weeks (3 weeks titration and 12 weeks maintenance) intervention 3: 10, 20, 30, 40, 50 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)
|
intervention 1: Tapentadol ER (100 to 250 mg twice daily) intervention 2: Matching Placebo (twice daily) intervention 3: Oxycodone CR (20 to 50 mg twice daily)
| 100
|
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Mitterdorf | N/A | Austria | 13.35041 | 48.16723
Salzburg | N/A | Austria | 13.04399 | 47.79941
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Wiener Neustadt | N/A | Austria | 16.23196 | 47.80485
Karlovac | N/A | Croatia | 15.55 | 45.49167
Osijek | N/A | Croatia | 18.69389 | 45.55111
Sisak | N/A | Croatia | 16.37833 | 45.46611
Zagreb | N/A | Croatia | 15.97798 | 45.81444
Zagreb | N/A | Croatia | 15.97798 | 45.81444
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Dresden | N/A | Germany | 13.73832 | 51.05089
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Hamburg | N/A | Germany | 9.99302 | 53.55073
Leipzig | N/A | Germany | 12.37129 | 51.33962
Magdeburg | N/A | Germany | 11.62916 | 52.12773
Schwerin | N/A | Germany | 11.41316 | 53.62937
Wiesbaden | N/A | Germany | 8.24932 | 50.08258
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Debrecen | N/A | Hungary | 21.62444 | 47.53167
Kecskemét | N/A | Hungary | 19.69128 | 46.90618
Kecskemét | N/A | Hungary | 19.69128 | 46.90618
Visegrád | N/A | Hungary | 18.9709 | 47.78526
Chieti | N/A | Italy | 14.16494 | 42.34827
Milan | N/A | Italy | 12.59836 | 42.78235
Pavia | N/A | Italy | 9.15917 | 45.19205
Perugia | N/A | Italy | 12.38878 | 43.1122
Bauska | N/A | Latvia | 24.19443 | 56.40794
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Losser | N/A | Netherlands | 7.00417 | 52.26083
Oude Pekela | N/A | Netherlands | 7.00972 | 53.10417
s'Hertogenbosch | N/A | Netherlands | N/A | N/A
Spijkenisse | N/A | Netherlands | 4.32917 | 51.845
Bielsko-Biala | N/A | Poland | 19.04686 | 49.82245
Gmina Końskie | N/A | Poland | 20.40607 | 51.19166
Katowice | N/A | Poland | 19.02754 | 50.25841
Krakow | N/A | Poland | 19.93658 | 50.06143
Lublin | N/A | Poland | 22.56667 | 51.25
Mielec | N/A | Poland | 21.4239 | 50.28709
Piekary Śląskie | N/A | Poland | 18.92653 | 50.38017
Rzeszów | N/A | Poland | 21.99901 | 50.04132
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Wroclaw | N/A | Poland | 17.03333 | 51.1
Coimbra | N/A | Portugal | -8.41955 | 40.20564
Faro | N/A | Portugal | -7.92716 | 37.01869
Funchal | N/A | Portugal | -16.92547 | 32.66568
Guimarães | N/A | Portugal | -8.29619 | 41.44443
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Ponta Delgada | N/A | Portugal | -25.66874 | 37.73952
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Campulung Muscel | N/A | Romania | 25.05 | 45.26667
Craiova | N/A | Romania | 23.8 | 44.31667
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Košice | N/A | Slovakia | 21.25808 | 48.71395
Poprad | N/A | Slovakia | 20.29798 | 49.06144
Prešov | N/A | Slovakia | 21.23393 | 48.99839
Rimavská Sobota | N/A | Slovakia | 20.02239 | 48.38284
Alicante | N/A | Spain | -0.48149 | 38.34517
Benidorm | N/A | Spain | -0.13098 | 38.53816
L'Hospitalet de Llobregat | N/A | Spain | 2.10028 | 41.35967
La Roca del Vallès | N/A | Spain | 2.33333 | 41.58333
Málaga | N/A | Spain | -4.42034 | 36.72016
Móstoles | N/A | Spain | -3.86496 | 40.32234
Oviedo | N/A | Spain | -5.84476 | 43.36029
Oviedo | N/A | Spain | -5.84476 | 43.36029
Seville | N/A | Spain | -5.97317 | 37.38283
Torrelavega | N/A | Spain | -4.04785 | 43.34943
Valencia | N/A | Spain | -0.37966 | 39.47391
Vic | N/A | Spain | 2.25486 | 41.93012
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Blackpool | N/A | United Kingdom | -3.05 | 53.81667
Bradford | N/A | United Kingdom | -1.75206 | 53.79391
Cardiff | N/A | United Kingdom | -3.18 | 51.48
Chesterfield | N/A | United Kingdom | -1.41667 | 53.25
Chorley | N/A | United Kingdom | -2.61667 | 53.65
Ecclesfield | N/A | United Kingdom | -1.4652 | 53.43975
Falkirk | N/A | United Kingdom | -3.78535 | 56.0021
Kenton | N/A | United Kingdom | -3.47151 | 50.63978
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Reading | N/A | United Kingdom | -0.97113 | 51.45625
Solihull | N/A | United Kingdom | -1.78094 | 52.41426
Woolpit | N/A | United Kingdom | 0.88826 | 52.22454
| 0
|
NCT00486811
|
[
3
] | 238
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
This is a study designed to evaluate the efficacy, safety, and tolerability of RGH-188 monotherapy in the treatment of acute mania. This study will be 5 weeks in duration; 3 weeks double-blind treatment and 2-weeks safety follow-up. All patients meeting the eligibility criteria will be randomized to one of two treatment groups: RGH-188 or placebo
| null |
Bipolar Disorder
|
Mania Bipolar I Disorder Acute Mania Associated with Bipolar I Disorder
| null | 2
|
arm 1: Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks. arm 2: Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Cariprazine 3 mg - 12 mg oral administration, once per day. intervention 2: Dose-matched placebo oral administration, once per day.
|
intervention 1: Cariprazine (RGH-188) intervention 2: Placebo
| 1
|
St Louis | Missouri | United States | -90.19789 | 38.62727
| 0
|
NCT00488618
|
[
3
] | 67
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this exploratory study is to assess the efficacy and safety of nesiritide in participants with acute (a quick and severe form of illness in its early stage) heart failure (when the heart inadequately pumps blood through the body) including acute exacerbation of chronic (lasting a long time) heart failure, administered intravenous (into a vein) bolus (a large amount) followed by intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle).
|
This is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), multi-center (when more than 1 hospital or medical school team work on a medical research study), randomized (study medication assigned by chance), stepwise, bolus plus intravenous infusion, fixed-flexible (arbitrary dose titration \[slow increase in drug dosage, guided by participant's responses\]) study. The study consists of 3 periods: Observation period (from the time of obtaining consent to the start of study treatment), Treatment period, and Follow-up period (from 24 hours after the initiation of study treatment \[discontinuation\] to 30 days after the initiation of study treatment). The participants will be randomly assigned to 1 of the following 3 treatment groups: 2+0.005 group, 1+0.01 group and 2+0.01 group. The treatment period consists of treatment with bolus injection (over 1 minute) followed by intravenous infusion (over 24 hours: Period 1 \[fixed-dose period\] of 3 hours and Period 2 \[flexible-dose period\] of 21 hours).The study will be conducted stepwise and hence, initially participants will be randomly assigned to 1 of the following 2 groups: 1+0.01 group and 2+0.005 group. Participants will receive nesiritide at an initial dose of 0.005 or 0.01 microgram per kilogram per minute (mcg/kg/min), and the dose escalation of 0.005 mcg/kg/min per dose will be conducted every 3 hours up to maximum of 0.03 mcg/kg/min in Period 2. Safety data of at least 5 participants will be assessed for each group, and after confirming the safety of 2 groups, the participants will be assigned to third group of nesiritide 2 microgram per kilogram (mcg/kg) +0.01 mcg/kg/min. Then participants will be followed up to a maximum of 30 days after the initiation of study treatment, in follow-up period. Participants will primarily be evaluated for the effect of nesiritide on hemodynamic parameters such as pulmonary capillary wedge pressure (PCWP), or if it is unmeasurable then it will be complemented with pulmonary arterial diastolic pressure (PADP). Participants' safety will also be monitored throughout the study.
|
Heart Failure, Congestive
|
Heart failure, congestive Nesiritide and JNS004
| null | 3
|
arm 1: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 15.4 to 35.2 mcg/kg. arm 2: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 9.2 to 31.7 mcg/kg. arm 3: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 16.4 to 36.2 mcg/kg.
|
[
0,
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 15.4 to 35.2 mcg/kg. intervention 2: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 9.2 to 31.7 mcg/kg. intervention 3: Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 16.4 to 36.2 mcg/kg.
|
intervention 1: Nesiritide (1+0.01) intervention 2: Nesiritide (2+0.005) intervention 3: Nesritide (2+0.01)
| 11
|
Amagasaki | N/A | Japan | 135.41667 | 34.71667
Chikushino-shi | N/A | Japan | 130.5156 | 33.49631
Hiroshima | N/A | Japan | 132.45 | 34.4
Ikoma | N/A | Japan | 135.7 | 34.68333
Komatsushima | N/A | Japan | 140.88696 | 38.28306
Kumamoto | N/A | Japan | 130.69181 | 32.80589
Moriyama | N/A | Japan | 135.98333 | 35.06667
Osaka | N/A | Japan | 135.50107 | 34.69379
Saitama | N/A | Japan | 139.65657 | 35.90807
Tokyo | N/A | Japan | 139.69171 | 35.6895
Yokohama | N/A | Japan | 139.65 | 35.43333
| 0
|
NCT00490724
|
[
5
] | 35
|
NON_RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Chronic hepatitis C virus (HCV) infection is common in dialysis patients. Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. Two meta-analyses evaluating the efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29.6%, respectively. The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis patients showed conflicting results, with a more favorable outcome of patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly tolerated), Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,and have low response rates under the concomitant use of immunosuppressive agents.
Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of treatment.In addition, a recent study including 6 patients with combination of pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%.
Although dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN monotherapy than patients with normal renal function for HCV therapy. More than half of these patients are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with normal renal function by combined pegylated IFN alfa plus ribavirin who fail to response to IFN monotherapy has achieved a SVR rate of 28%. Based on the long-term favorable outcome in dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients who fail to achieve HCV eradication by conventional or pegylated IFN alfa.
|
Chronic hepatitis C virus (HCV) infection is common in dialysis patients, with the reported prevalence varying from 3% to 80% worldwide.(1-3) Although these patients usually have mild symptoms and moderate elevation of alanine transaminase levels, recent international collaborative survey and prospective studies found that anti-HCV seropositivity and positive HCV RNA were risk factors for mortality and hepatocellular carcinoma (HCC).(4-7) Furthermore, progressive hepatic fibrosis, poor patient and graft survival were observer in dialysis patients with HCV infection who undergo renal transplantation (RT), suggesting immunosuppression following RT may worsen the course of hepatic fibrosis and renal graft function.(8-13) These lines of evidence indicate that HCV infection in the dialysis population is an important issue to be tackled.
Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. In dialysis patients, treatment with conventional or pegylated interferon has also received much attention recently. Two meta-analyses evaluating the efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29.6%, respectively.(14,15) The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis patients showed conflicting results, with a more favorable outcome of patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly tolerated),(16-21) which may result from different pharmacokinetic profiles between these two pegylated IFNs. Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,(22,23) and have low response rates under the concomitant use of immunosuppressive agents.(24,25) Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of treatment.(26-28) In addition, a recent study including 6 patients with combination of pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%.(29) Although dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN monotherapy than patients with normal renal function for HCV therapy. More than half of these patients are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with normal renal function by combined pegylated IFN alfa plus ribavirin who fail to response to IFN monotherapy has achieved a SVR rate of 28%.(30) Based on the long-term favorable outcome in dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients who fail to achieve HCV eradication by conventional or pegylated IFN alfa.
|
Chronic Hepatitis C Hemodialysis
|
Chronic hepatitis C hemodialysis interferon ribavirin
| null | 2
|
arm 1: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 48 weeks for HCV genotype 1 arm 2: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 weeks for HCV genotype 2
|
[
0,
0
] | 2
|
[
0,
0
] |
intervention 1: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 48 weeks intervention 2: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 weeks
|
intervention 1: Pegylated interferon alfa-2a and ribavirin intervention 2: Pegylated interferon alfa-2a and ribavirin
| 1
|
Taipei | N/A | Taiwan | 121.52639 | 25.05306
| 0
|
NCT00491179
|
[
3
] | 83
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to see whether a new type of anti-cancer drug, known as BAY 43-9006, can be given safely and with good effect in combination with dacarbazine (DTIC). DTIC is the current standard chemotherapy drug given for melanoma that has spread through the body. Although this drug can be effective on its own and is generally well tolerated, not all patients will benefit, so there is a need to test new drugs and drug combinations for treating melanoma.
|
Issues on "Safety" outcomes are addressed in the Adverse Event section.
|
Melanoma
| null | 1
|
arm 1: Dacarbazine 1000 mg/m\^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)
|
[
0
] | 1
|
[
0
] |
intervention 1: Dacarbazine 1000 mg/m\^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)
|
intervention 1: Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC)
| 12
|
Bordeaux | N/A | France | -0.5805 | 44.84044
Lyon | N/A | France | 4.84671 | 45.74846
Toulouse | N/A | France | 1.44367 | 43.60426
Villejuif | N/A | France | 2.35992 | 48.7939
Cambridge | Cambridgeshire | United Kingdom | 0.11667 | 52.2
Southampton | Hampshire | United Kingdom | -1.40428 | 50.90395
London | London | United Kingdom | -0.12574 | 51.50853
London | London | United Kingdom | -0.12574 | 51.50853
London | London | United Kingdom | -0.12574 | 51.50853
Manchester | Manchester | United Kingdom | -2.23743 | 53.48095
Northwood | Middlesex | United Kingdom | -0.42454 | 51.61162
Sutton | Surrey | United Kingdom | -0.2 | 51.35
| 0
|
NCT00492297
|
|
[
5
] | 16
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This study will last up to 9 weeks. Subjects will visit the clinic up to 14 times. Certain clinic visits will include a physical examination, lung function tests, inflammatory cell analysis from nasal secretions and/or sputum, and blood draws. Subjects will inhale an FDA approved virus through their nose which is known to cause the common cold. All study related medications and medical examinations will be provided at no cost to the subject. The drugs used in this study are approved for the age group under study.
| null |
Asthma
|
Rhinovirus Asthma
| null | 3
|
arm 1: None arm 2: None arm 3: None
|
[
1,
1,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: comparator intervention 2: Comparator intervention 3: Placebo
|
intervention 1: fluticasone propionate/salmeterol intervention 2: fluticasone propionate intervention 3: placebo
| 1
|
Charlottesville | Virginia | United States | -78.47668 | 38.02931
| 0
|
NCT00503009
|
[
3
] | 220
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The current study is designed to test the efficacy, safety and tolerability of LCP-AtorFen, a combination of atorvastatin and fenofibrate.
|
This is a multicenter, randomized, double-blind, 12 week study with a 52-week open-label follow-up to evaluate the safety and efficacy of LCP-AtorFen (the combination of atorvastatin and fenofibrate) in the treatment of hyperlipidemia.
After a wash-out phase, eligible patients will be randomized on a 1:1:1 ratio to either LCP-AtorFen, atorvastatin or fenofibrate for 12 weeks. After the completion of the 12-week phase, all eligible patients will be offered to receive open-label LCP-AtorFen for another 52 weeks.
|
Dyslipidemia
|
LCP-AtorFen Non-HDL cholesterol Triglycerides HDL cholesterol LDL cholesterol Atorvastatin Fenofibrate
| null | 3
|
arm 1: LCP-AtorFen 40/100mg fixed-dose combination tablet of 40mg atorvastatin and 145mg fenofibrate for treatment of mixed dyslipidemia arm 2: atorvastatin 40mg tablet (Lipitor), as an adjunct to diet and exercise for treatment of mixed dyslipidemia arm 3: fenofibrate 145mg tablet (Tricor), as an adjunct to diet and exercise for treatment of mixed dyslipidemia
|
[
0,
1,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: 40mg atorvastatin combined with 100mg fenofibrate in a tablet for once daily treatment of dyslipidemia and mixed dyslipidemia intervention 2: dyslipidemia and mixed dyslipidemia intervention 3: dyslipidemia and mixed dyslipidemia
|
intervention 1: LCP-AtorFen intervention 2: atorvastatin intervention 3: fenofibrate
| 1
|
Chicago | Illinois | United States | -87.65005 | 41.85003
| 0
|
NCT00504829
|
[
3,
4
] | 352
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The purpose of this study is to determine the efficacy and safety of Perampanel in patients with painful diabetic neuropathy.
|
This is a randomized, double-blind, placebo-controlled, parallel-group study. This is a 5-arm, 21-week study comprised of up to a 2-week Screening period, a 15-week Dose-Escalation and Maintenance Phase using 4 doses of E2007 (2 mg, 4 mg, 6 mg, and 8 mg) or placebo, and a 4-week, single-blind placebo Follow-Up Phase. Patients will be randomly assigned to one of the five treatment groups. Those patients assigned to receive either 4 mg, 6 mg, or 8 mg E2007 will be escalated to the appropriate dose according to an escalation schedule. All patients will take four identical-looking tablets on a daily basis for the entire study duration for blinding purposes.
|
Diabetic Neuropathy
|
Diabetic neuropathy
| null | 5
|
arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None
|
[
2,
1,
1,
1,
1
] | 5
|
[
0,
0,
0,
0,
0
] |
intervention 1: Placebo tablets, once daily, for 15 weeks (taken orally). intervention 2: Perampanel, 2 mg once daily, for 15 weeks (taken orally). intervention 3: Perampanel, 2 mg once daily for three weeks, followed by 4 mg, once daily, for 12 weeks (taken orally). intervention 4: Perampanel, 2 mg once daily for three weeks, followed by 4 mg once daily, for three weeks and 6 mg, once daily, for nine weeks (taken orally). intervention 5: Perampanel, 2 mg once daily, for three weeks, followed by 4 mg, once daily for three weeks, 6 mg once daily for three weeks and 8 mg, once daily, for six weeks (taken orally).
|
intervention 1: Placebo intervention 2: E2007 (2 mg) intervention 3: E2007 (4 mg) intervention 4: E2007 (6 mg) intervention 5: E2007 (8 mg)
| 1
|
Chicago | Illinois | United States | -87.65005 | 41.85003
| 0
|
NCT00505284
|
[
5
] | 23
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This trial is conducted in Europe. The purpose of this trial is to investigate if there is any change in the mechanism of energy expenditure (i.e. the way in which energy is used) in patients with type 1 diabetes, whilst taking two different, commercially available insulins for the treatment of their diabetes.
|
The study had been temporarily halted due to an unplanned interim analysis. The Sponsor is now aware that a further interim analysis has been performed by the site and therefore a decision has been made not to recommence the study
|
Diabetes Diabetes Mellitus, Type 1
| null | 2
|
arm 1: Insulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart arm 2: Insulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
|
[
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection intervention 2: Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection intervention 3: Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
|
intervention 1: insulin detemir intervention 2: insulin NPH intervention 3: insulin aspart
| 1
|
Guildford | N/A | United Kingdom | -0.57427 | 51.23536
| 0
|
NCT00509925
|
|
[
5
] | 23
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
The aim of the present study is to investigate whether the effects of salmeterol in combination with fluticasone propionate on blood markers of airway inflammation are maintained after chronic dosing and whether the effect is influenced by the time of allergen challenge relative to the time of dosing.
|
A 12-week, randomised, double-blind, placebo-controlled, three-period, cross-over pilot study comparing the effect of salmeterol/fluticasone propionate, fluticasone propionate and placebo on perpheral blood eosinophils and serum IL-5 in response to allergen challenge in asthma subjects when allergen challenge is administered at 1 hour or 11-12 hours post-dose of the dosing interval
|
Asthma
|
asthma allergen challenge IL-5 eosinophils
| null | 6
|
arm 1: Fluticasone Propionate (FP) 100 micrograms (mcg) twice daily (BID) in the first treatment period: Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID in the second treatment period: Placebo in the third treatment period arm 2: Placebo in the first treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period arm 3: Salmeterol/Fluticasone Propionate 50/100 Combination mcg BID in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Placebo in the third treatment period arm 4: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the first treatment period: Placebo in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period arm 5: Fluticasone Propionate 100 mcg BID in the first treatment period: Placebo in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period arm 6: Placebo in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period
|
[
0,
0,
0,
0,
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Fluticasone Propionate 100 mcg BD intervention 2: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD intervention 3: Matching Placebo
|
intervention 1: FP intervention 2: SFC intervention 3: Placebo
| 2
|
Madison | Wisconsin | United States | -89.40123 | 43.07305
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
| 0
|
NCT00517634
|
[
4
] | 248
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
Anal fissure is a solitary ulcer in the squamous epithelium of the anus causing intense anal pain especially during defecation and for 1 or 2 hours afterwards. There are no approved drugs in the United States (US) for this condition and surgery is often the treatment choice. Strakan is conducting this confirmatory study so the product can be submitted for regulatory approval in the US. Strakan currently markets this product throughout Europe.
The objective of this study is to determine the effect of nitroglycerin ointment 0.4% (Cellegesic) versus placebo on average pain intensity over every 24 hour period for up to 21 days of treatment in 250 patients.
| null |
Fissure in Ano Pain
|
Pain associated with chronic anal fissure
| null | 2
|
arm 1: Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days. arm 2: Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Cellegesic was supplied as an ointment containing 0.4% w/w nitroglycerin. intervention 2: Placebo was supplied as an ointment identical to Cellegesic ointment except that it contained no nitroglycerin.
|
intervention 1: Cellegesic intervention 2: Placebo
| 0
| null | 0
|
NCT00522041
|
[
5
] | 122
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| true
| 0ALL
| true
|
This is a post-market medical device study. This study will compare best medical practice with or without adjunctive VNS Therapy in patients who are 16 years and older with pharmacoresistant partial epilepsy.
|
This is a post-market medical device study. This study will compare best medical practice with or without adjunctive VNS Therapy in patients who are 16 years and older with pharmaco-resistant partial epilepsy. The Sponsor, Cyberonics, provides funding for this study. Patients are followed for 26 months, 24 of those months are following the initiation of treatment. No study sites will be permitted to enroll study subjects until Institutional Review Board (IRB)/Ethics Committee (EC) approval has been received.
|
Epilepsy Partial Epilepsy
|
Epilepsy VNS Therapy
| null | 2
|
arm 1: VNS Therapy + Best Medical Practice arm 2: Best Medical Practice
|
[
0,
1
] | 2
|
[
1,
0
] |
intervention 1: VNS Therapy + Best Medical Practice including anti-epileptic drugs intervention 2: Best Medical Practice including anti-Epileptic Drugs
|
intervention 1: Vagal Nerve Simulation (VNS) Therapy intervention 2: Best Medical Practive
| 48
|
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Calgary | Alberta | Canada | -114.08529 | 51.05011
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Grenoble | N/A | France | 5.71479 | 45.17869
Lille | N/A | France | 3.05858 | 50.63297
Lyon | N/A | France | 4.84671 | 45.74846
Montpellier | N/A | France | 3.87635 | 43.61093
Paris | N/A | France | 2.3488 | 48.85341
Strasbourg | N/A | France | 7.74553 | 48.58392
Tours | N/A | France | 0.70398 | 47.39484
Bonn | N/A | Germany | 7.09549 | 50.73438
Erlangen | N/A | Germany | 11.00783 | 49.59099
Greifswald | N/A | Germany | 13.40244 | 54.08905
Kehl-Kork | N/A | Germany | N/A | N/A
Marburg | N/A | Germany | 8.77069 | 50.80904
Radeberg | N/A | Germany | 13.91199 | 51.11112
Ancona | N/A | Italy | 13.5103 | 43.60717
Bologna | N/A | Italy | 11.33875 | 44.49381
Florence | N/A | Italy | 11.24626 | 43.77925
Milan | N/A | Italy | 12.59836 | 42.78235
Monserrato | N/A | Italy | 9.1444 | 39.25642
Pisa | N/A | Italy | 10.4036 | 43.70853
Pontedera | N/A | Italy | 10.63067 | 43.66141
Reggio Calabria | N/A | Italy | 15.66129 | 38.11047
Roma | N/A | Italy | 11.10642 | 44.99364
Torino | N/A | Italy | 11.99138 | 44.88856
Blaricum | N/A | Netherlands | 5.24167 | 52.2725
Enschede | N/A | Netherlands | 6.89583 | 52.21833
Heemstede | N/A | Netherlands | 4.62301 | 52.34992
Oosterhout | N/A | Netherlands | 4.85972 | 51.645
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Sandvika | N/A | Norway | 13.59125 | 64.46377
Madrid | N/A | Spain | -3.70256 | 40.4165
Santiago de Compostela | N/A | Spain | -8.54569 | 42.88052
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Lund | N/A | Sweden | 13.19321 | 55.70584
Umeå | N/A | Sweden | 20.25972 | 63.82842
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Cambridge | N/A | United Kingdom | 0.11667 | 52.2
Fazakerley | N/A | United Kingdom | -2.92863 | 53.4614
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
| 0
|
NCT00522418
|
[
3
] | 186
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
The purpose of this study is to evaluate if topical ASC-J9 cream is effective in treating acne.
|
Subjects with acne were randomized to one of four treatment groups for twice daily topical dosing to the face for 12 weeks. Assessments of acne status were performed at Baseline, Weeks 2, 4, 8 and 12 and then 4 weeks after the last dose of study drug.
|
Acne Vulgaris
|
acne
| null | 4
|
arm 1: Vehicle control cream applied topically to the face twice daily for 12 weeks arm 2: 0.001% ASC-J9 cream applied topically to the face twice daily for 12 weeks arm 3: 0.005% ASC-J9 cream applied topically to the face twice daily for 12 weeks arm 4: 0.025% ASC-J9 cream applied topically to the face twice daily for 12 weeks
|
[
2,
0,
0,
0
] | 2
|
[
0,
0
] |
intervention 1: Topical application to the face twice daily for 12 weeks. intervention 2: vehicle control applied topically twice daily for 12 weeks
|
intervention 1: ASC-J9 cream intervention 2: placebo
| 10
|
Fremont | California | United States | -121.98857 | 37.54827
San Diego | California | United States | -117.16472 | 32.71571
Boise | Idaho | United States | -116.20345 | 43.6135
Paramus | New Jersey | United States | -74.07542 | 40.94454
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Austin | Texas | United States | -97.74306 | 30.26715
Bryan | Texas | United States | -96.36996 | 30.67436
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Lynchburg | Virginia | United States | -79.14225 | 37.41375
| 0
|
NCT00525499
|
[
3
] | 100
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
Phase 2 study to evaluate three dose levels of SKY0402 compared with 75 mg of bupivacaine HCl.
|
Effective postoperative pain control is a critical element in patient recovery, as the majority of patients may experience significant pain, particularly in the first few days following surgery. Appropriate postoperative pain management contributes to improved healing, faster patient mobilization, shortened hospital stays, and reduced healthcare costs.
|
Postoperative Pain
|
hemorrhoidectomy pain Postoperative analgesia
| null | 4
|
arm 1: SKY0402, single administration arm 2: SKY0402, single administration arm 3: SKY0402, single administration arm 4: Bupivacaine HCl
|
[
0,
0,
0,
1
] | 2
|
[
0,
0
] |
intervention 1: SKY0402 intervention 2: Bupivacaine HCl
|
intervention 1: SKY0402 intervention 2: Bupivacaine HCl
| 7
|
San Clemente | California | United States | -117.61199 | 33.42697
Miami | Florida | United States | -80.19366 | 25.77427
Houston | Texas | United States | -95.36327 | 29.76328
Tacoma | Washington | United States | -122.44429 | 47.25288
Kutaisi | N/A | Georgia | 42.69459 | 42.26791
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
| 0
|
NCT00529126
|
[
4
] | 1,613
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This study is designed to investigate the efficacy, safety and tolerability of aliskiren 300 mg, 150 mg and 75 mg when compared to ramipril 5 mg in patients with essential hypertension.
| null |
Hypertension
|
Hypertension, Aliskiren, Ramipril
| null | 4
|
arm 1: Aliskiren 300 mg once daily arm 2: Aliskiren 150 mg once daily arm 3: Aliskiren 75 mg once daily arm 4: Ramipril 5 mg once daily
|
[
0,
0,
0,
1
] | 2
|
[
0,
0
] |
intervention 1: Aliskiren intervention 2: comparator
|
intervention 1: Aliskiren intervention 2: Ramipril
| 3
|
China | N/A | China | N/A | N/A
India | N/A | India | 75.36261 | 23.01533
Thailand | N/A | Thailand | N/A | N/A
| 0
|
NCT00529451
|
[
5
] | 201
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| null |
The purpose of this study is to evaluate medication satisfaction after at least 4 weeks of paliperidone ER (extended-release), an antipsychotic, treatment in patients with schizophrenia who were previously taking either 4 or 6 mg of risperidone daily by mouth, but who are not satisfied with their treatment.
|
Paliperidone ER has been shown to be effective compared to placebo ("a sugar pill") in the acute treatment and maintenance of patients with schizophrenia. Paliperidone ER combines an active metabolite of another antipsychotic, risperidone, with manufacturing technology allowing more gradual release of the drug and less difference in high and low blood levels of the drug. Side effects to medications are sometimes due to wide differences in these high and low blood levels. Recent research has shown that many patients with schizophrenia discontinue their antipsychotic medication due to "subject-choice". Therefore, it is important that research studies attempt to measure patients' satisfaction with antipsychotic medication, in addition to measuring how they respond on tests of effectiveness. This study has been designed to evaluate antipsychotic medication satisfaction in patients who continue to have symptoms of schizophrenia, and who say they are dissatisfied with their current risperidone treatment. The primary outcome is the change in the Medication Satisfaction Questionnaire (MSQ) score, from baseline to the Week 6 endpoint. These patients are randomized (like flipping a coin) as to when their risperidone (4 mg to 6 mg per day) is switched to paliperidone ER. Because the study is 'blinded', neither the study doctor nor the patient will know when treatment with risperidone is stopped and treatment with paliperidone ER begins. Throughout the study all patients continue to receive antipsychotic medication daily. Patients will continue on the same daily dose of risperidone until their randomly assigned switch to paliperidone ER. All patients will be switched to paliperidone ER over the course of study and once switched continue to take paliperidone ER for the remainder of the study. Paliperidone ER is started at 6 mg/day and can be increased to 9 mg/day or 12 mg/day at the doctor's discretion. Effectiveness and safety will be measured at visits scheduled weekly for the first four weeks and then at the Week 6 endpoint. At each visit, patients will be asked to complete psychiatric tests and questionnaires that will measure effectiveness and patient satisfaction with the medicine. They will also complete tests and evaluations for safety, including electrocardiograms (ECGs, electrical tracings of the heart) and blood samples at the beginning and end of the study. Each patient receives two blinded capsules by mouth once daily in the morning for 6 weeks. Patients taking risperidone receive either a 4-mg or 6-mg capsule plus a placebo capsule. When patients are switched, Paliperidone ER is started at 6 mg/day the day after risperidone is discontinued and can be increased to 9 mg/day or 12 mg/day at the doctor's discretion. Paliperidone 3-mg and 6-mg capsules are combined with placebo to equal the total dose in two capsules.
|
Schizophrenia
|
schizophrenia medication satisfaction, Invega
| null | 2
|
arm 1: Oral Risperidone 4 or 6 mg MG once daily for 0-2 weeks arm 2: Paliperidone ER 6, 9 or 12 MG once daily for 4-6 weeks
|
[
0,
0
] | 2
|
[
0,
0
] |
intervention 1: 4 or 6 mg MG once daily for 0-2 weeks intervention 2: 6, 9 or 12 MG once daily for 4-6 weeks
|
intervention 1: Oral Risperidone intervention 2: Paliperidone ER
| 40
|
Cerritos | California | United States | -118.06479 | 33.85835
Garden Grove | California | United States | -117.94145 | 33.77391
Huntington Beach | California | United States | -117.99923 | 33.6603
Pico Rivera | California | United States | -118.09673 | 33.98307
San Diego | California | United States | -117.16472 | 32.71571
Santa Ana | California | United States | -117.86783 | 33.74557
Torrance | California | United States | -118.34063 | 33.83585
Atlanta | Georgia | United States | -84.38798 | 33.749
Chicago | Illinois | United States | -87.65005 | 41.85003
Flowood | Mississippi | United States | -90.13898 | 32.30959
Clementon | New Jersey | United States | -74.98294 | 39.8115
Brooklyn | New York | United States | -73.94958 | 40.6501
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Austin | Texas | United States | -97.74306 | 30.26715
Irving | Texas | United States | -96.94889 | 32.81402
Miami | FL | Argentina | N/A | N/A
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Ciudad Autonoma de | N/A | Argentina | N/A | N/A
Cordoba Crd | N/A | Argentina | N/A | N/A
Mendoza | N/A | Argentina | -68.84582 | -32.88946
Mendoza Men | N/A | Argentina | N/A | N/A
Rosario | N/A | Argentina | -60.63932 | -32.94682
Barranquilla | N/A | Colombia | -74.78132 | 10.96854
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Bogotá S/N | N/A | Colombia | N/A | N/A
Bucaramanga S/N | N/A | Colombia | N/A | N/A
Pilsen | N/A | Czechia | 13.37759 | 49.74747
Prague | N/A | Czechia | 14.42076 | 50.08804
Sternberk | N/A | Czechia | 17.29889 | 49.73044
Bojnice | N/A | Slovakia | 18.5864 | 48.78511
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Michalovce | N/A | Slovakia | 21.9195 | 48.75434
Rimavská Sobota | N/A | Slovakia | 20.02239 | 48.38284
Žilina | N/A | Slovakia | 18.73941 | 49.22315
Dnipropetrovsk | N/A | Ukraine | 35.04066 | 48.46664
Donetsk | N/A | Ukraine | 37.80224 | 48.023
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Lviv | N/A | Ukraine | 24.02324 | 49.83826
Odesa | N/A | Ukraine | 30.74383 | 46.48572
Village Stepanovka Kherson | N/A | Ukraine | N/A | N/A
| 0
|
NCT00535132
|
[
2
] | 103
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
A study to assess the safety and efficacy of sitagliptin 100mg compared to sitagliptin 200mg in patients with type 2 diabetes.
| null |
Type 2 Diabetes
| null | 3
|
arm 1: sitagliptin 100 mg arm 2: sitagliptin 200 mg arm 3: Placebo
|
[
0,
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: sitagliptin 100 mg tablets q.d. (once daily) for 7 days. intervention 2: sitagliptin 200 mg tablets q.d. (once daily) for 7 days. intervention 3: sitagliptin 100 mg \& 200 mg matching Placebo tablets q.d. (once daily) for 7 days.
|
intervention 1: sitagliptin phosphate intervention 2: sitagliptin phosphate intervention 3: Comparator: Placebo
| 0
| null | 0
|
NCT00541229
|
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