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AUTHOR CONTRIBUTIONS
PMC10632612
CONFLICT OF INTEREST STATEMENT
Andrew H. Talal has received honoraria and funds to his institution from Gilead Sciences and Abbvie Inc. The other authors declare no conflict of interest.
PMC10632612
ETHICS STATEMENT
This study was approved by the University at Buffalo Institutional Review Board (IRB) and by IRBs at each of the sites where the study was conducted. All participants provided written informed consent before study participation.
PMC10632612
ACKNOWLEDGEMENTS
The authors thank the study participants for their participation and the staff at each of the study sites. The authors also acknowledge Darlene Meyer for interviewing assistance, Ravi Krishnan, and Harrison He for assistance with transcript verification. This work was supported by a Patient‐Centred Outcomes Research In...
PMC10632612
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
PMC10632612
REFERENCES
PMC10632612
Background
PONV, Postoperative nausea and vomiting
SIDE EFFECT
Postoperative nausea and vomiting (PONV) is a common side effect associated with general anesthesia. Both ondansetron and aprepitant been effectively used to prevent PONV. However, there is a disagreement of opinions regarding the superiority of these two drugs. This study aims to compare the efficacy of aprepitant wit...
PMC10717277
Methods
PONV
In this double-blinded clinical trial, 80 patients scheduled for orthognathic surgery at Imam Hossein Hospital, Tehran, Iran, were randomly assigned to two groups. A standardized anesthesia protocol was used for all patients. The first group received a placebo capsule administered one hour before the surgical procedure...
PMC10717277
Results
nausea, vomiting
There were no significant differences in demographic data between the two groups. Patients in the aprepitant group had a significantly lower incidence and severity of nausea (2.5% versus 27.5%), vomiting (5% versus 25%), and required fewer rescue medications (7.5% versus 62.5%) compared to the ondansetron group. Additi...
PMC10717277
Conclusion
PONV
According to the findings of this study, aprepitant has demonstrated a greater efficacy in preventing PONV following orthognathic surgery, when compared to ondansetron.
PMC10717277
Trial registration
Iranian Registry of Clinical Trials (IRCT code: IRCT20211205053279N3), date of registration: 16/12/2022.
PMC10717277
Keywords
PMC10717277
Introduction
PONV, emesis, nausea and vomiting, postoperative pain
SIDE EFFECT
Post-operative nausea and vomiting (PONV) is a common side effect of general anesthesia that can significantly decrease patient satisfaction. In fact, many patients find PONV more distressing than postoperative pain [Aprepitant is a highly selective neurokinin-1 (NK1) receptor and substance P antagonist. It is commonly...
PMC10717277
Methods
PMC10717277
Study design ethics, and patient population
PONV, hypersensitivity, abnormal liver or renal function
MOTION SICKNESS, HYPERSENSITIVITY
This study was a double-blinded, randomized clinical trial that was carried out in the oral and maxillofacial surgery department of Imam Hossein Hospital (Tehran-Iran). This study was approved by the Research Ethics Committees of the research institute of Dental sciences-Shahid Beheshti University of medical sciences a...
PMC10717277
Intervention
The first group received a placebo capsule administered one hour before the surgical procedure along with 4 mg (2 ml) of ondansetron intravenously after anesthesia induction. The second group was given 80 mg aprepitant capsules one hour before the surgery, followed by an injection of 2 ml intravenous distilled water af...
PMC10717277
Assessment of outcomes
PONV, nausea, vomiting
The duration of surgery and the total amount of administered narcotics were recorded. All patients were kept in PACU for two hours and while assessing their vital signs (BP, HR, and SPO2), the occurrence and severity of PONV were evaluated and recorded as the primary outcome. In addition, the feeling of nausea, the fre...
PMC10717277
Statics
nausea, vomiting
Based on Gan et al. [The data was analyzed using Statistical Package for Social Sciences (SPSS) software (version 21, SPSS INC., Chicago, IL, USA). Demographic and other patient characteristics were expressed as means ± standard deviations. Values < 0.05 were considered statistically significant. For analyzing patient ...
PMC10717277
Discussion
nausea, postoperative pain, anxiety, cancer, nausea and vomiting, vomiting, pain, hypoxemia, Nausea, PONV, depression, Diemensch
CANCER, ELECTROLYTE DISTURBANCE, COMPLICATIONS, COMPLICATION
Advancements in surgical techniques and the development of new anesthesia drugs have significantly reduced the occurrence of severe, life-threatening side effects. However, despite these improvements, the issue of PONV remains a persistent concern and none of the current antiemetic drugs has been able to resolve this s...
PMC10717277
Limitation
The current study had several limitations. First, the aprepitant was administered 60 min before the induction of anesthesia. Considering that it takes approximately 3 h for the oral aprepitant to reach the maximum blood concentration [
PMC10717277
Conclusion
postoperative nausea and vomiting
According to the findings of this study, aprepitant has demonstrated a greater efficacy in preventing postoperative nausea and vomiting following orthognathic surgery, when compared to ondansetron.
PMC10717277
Acknowledgements
This article derived from Sadaf Nasseri dental doctoral thesis. The authors would like to thank the Research Center of Shahid Beheshti University of Medical Sciences for providing support, and resources to succeed this study. We would like to thank Imam Hossein hospital operative room staffs for their collaboration and...
PMC10717277
Authors’ contributions
MA: substantial contributions to the conception and design of the work; interpretation of data; have drafted the work. AK: substantial contributions to the conception and design of the work; interpretation of data; have drafted the work. AS: the design of the work; analysis, interpretation of data; have drafted the wor...
PMC10717277
Funding
No funding was received in any forms.
PMC10717277
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10717277
Declarations
PMC10717277
Ethics approval and consent to participate
https://irct.ir/16/12/2022
This study was by the Ethics Committee of the research institute 0f Dental sciences-Shahid Beheshti University of medical sciences approved this study. The study registered at the Iranian Registry of Clinical Trials ( https://irct.ir/16/12/2022, IRCT20211205053279N3). All patients signed the informed consent form, and ...
PMC10717277
Consent for publication
Not applicable.
PMC10717277
Competing interests
The authors declare no competing interests.
PMC10717277
References
PMC10717277
Key words
PE, diabetes mellitus, Preeclampsia
SECONDARY, DIABETES MELLITUS, PREECLAMPSIA
Preeclampsia (PE) affects up to five times more women with pre-existing diabetes mellitus (PDM) than women without it. The present study aimed to identify the effect of the DASH diet on PE incidence (primary outcome) and blood pressure, glycated haemoglobin (GH), serum lipids, glutathione peroxidase (GP), C-reactive pr...
PMC10345782
Abbreviation
PMC10345782
Introduction
diabetes mellitus, GHS, hypertensive, Diabetes, weight loss
DIABETES MELLITUS, DIABETES MELLITUS (DM), SECONDARY, SYNDROMES, DIABETES
Gestational hypertensive syndromes (GHS) affect about 14 % of pregnancies worldwide. In Latin America and the Caribbean, they are responsible for 22 % of maternal deathsWomen with pre-existing diabetes mellitus (PDM), either type 1 or type 2, are considered to be at a higher risk of developing PE. With the increased pr...
PMC10345782
Experimental methods
PMC10345782
Design
The study was a randomised, controlled, single-blind, two-arm treatment trial. The women were not told which treatment group they were allotted to. The study protocol was registered on the Brazilian Clinical Trials Registration Platform (Rebec – RBR-4tbgv6).The study was conducted between November 2016 and March 2020 a...
PMC10345782
Participants
The study population consisted of pregnant women diagnosed with PDM before referral, whose diagnosis was confirmed by an endocrinologist at the study site according to the criteria of the Brazilian Society of DiabetesAll the women received prenatal care throughout pregnancy from a multidisciplinary team at MT/UFRJ. Dat...
PMC10345782
Randomisation
Upon enrolment, the women were randomly allocated to either the SDG or the DDG using a random number from a list prepared using Excel® 2007. The women who received an odd number were put in the SDG and the women with an even number were put in the DDG by the nutritionist. The pregnant women did not know which study gro...
PMC10345782
Nutritional intervention
fat-free milk, weight gain
COMPLICATIONS
The nutritional intervention for both groups occurred from enrolment to the end of pregnancy and included a minimum of six individual appointments with the nutritionist when individualised guidance was given according to the occurrence of maternal complications. To improve dietary adherence, the women from the DDG were...
PMC10345782
Standard diet
Diabetes
DIABETES
The standard diet was the diet already recommended in routine prenatal nutritional care at the study site, which is consistent with American Diabetes Association guidelines
PMC10345782
Adapted DASH diet
The DASH diet used in the study was the version translated into Portuguese and adapted to the Brazilian population by Saunders A comparison of the constituents of the standard and DASH diets applied in the present research was published in the study of Fagherazzi
PMC10345782
Anthropometric assessment
Weight measurements (kg) were taken at all the appointments using an electronic platform scale, and height (m) was measured using a stadiometer attached to the scale. Measurements were taken according to standard nursing practice at the study site
PMC10345782
Assessment of food consumption and dietary adherence
weight gain
Food intake was assessed in two 24 h recalls administered during the 3rd (between the 22nd and 24th gestational week) and 5th (between the 29th and 34th gestational week) nutritional appointments. Foods in the 24 h recalls were expressed in household measurements, which were then quantified in grams or millilitres per ...
PMC10345782
Biochemical assessment
Venous blood samples (10 ml) were collected after 8–12 h fasting at baseline and after 12 weeks of intervention at a specialised laboratory. Serum glycated haemoglobin concentration (%) was determined by turbidimetry, and total cholesterol (mg/dl), triglycerides (mg/dl), high-density lipoprotein cholesterol (HDL-c, mg/...
PMC10345782
Diagnosis of PE
hypertension, proteinuria
HYPERTENSION
PE was diagnosed by the medical team based on: the gradual development of hypertension (after the 20th gestational week) and the presence of proteinuria (>0⋅3 g protein excretion in 24 h urine), or chronic hypertension associated with proteinuriaThe risk of developing early PE, up to the 34th gestational week, was esti...
PMC10345782
Sociodemographic, biological and obstetric assessment
THYROID DISORDERS, HYPERTENSION, CHRONIC DISEASES
The characteristics evaluated were: partnership status (partnered/unpartnered), maternal age (years) skin colour (by self-classification – white/black or brown), household income (in multiples of the minimum wage, based on its 2019 value) and educational level (high school non-graduate/high school graduate or higher ed...
PMC10345782
Outcomes
SECONDARY
The primary outcome was the PE incidence (%). The secondary outcomes included systolic and diastolic blood pressure levels (mmHg), changes in glycated haemoglobin (%), total cholesterol (mg/dl), LDL-c (mg/dl), HDL-c (mg/dl), triglycerides (mg/dl), CRP (mg/dl) and glutathione peroxidase (μmol/l). All secondary outcomes ...
PMC10345782
Sample size
HYPERTENSIVE DISORDER
The sample size was calculated based on the primary outcome (prevalence of hypertensive disorders of pregnancy) using G*Power
PMC10345782
Statistical analysis
Data distribution was evaluated by the Shapiro–Wilk test and visual inspection. The sample was described using mean and standard deviation, median and interquartile range, or relative and absolute frequencies. To identify differences in the general characteristics and dietary intake of the groups, the Student's The PE ...
PMC10345782
Ethical issues
All the women in the study signed an informed consent form and the project was approved by the ME/UFRJ research ethics committee on 07/31/15 (CAAE 47335515.0.0000.5275). The study was registered in the Brazilian Clinical Trials Registration Platform (Rebec – RBR-4tbgv6) and was conducted according to the guidelines lai...
PMC10345782
Discussion
T1DM, cardiovascular disease, TohdiniThe, GDM, Diabetes, diabetes
HIGH-RISK PREGNANCIES, CARDIOVASCULAR DISEASE, GDM, DIABETES, HYPERTENSIVE DISORDER, OXIDATIVE STRESS, HYPERTENSION, DIABETES
No differences between the group that received the standard diet and the group that received the adapted DASH diet were observed for the incidence of PE during the intervention. DDG showed an increase in serum concentrations of glutathione peroxidase and both diets contributed to a reduction of glycated haemoglobin. As...
PMC10345782
Acknowledgements
P., preeclampsia
PREECLAMPSIA
Lenita Zajdenverg and Marcus Miranda for their collaboration in the interpretation of the preeclampsia cases, and Joffre Amin Jr and Jorge Rezende Filho for their support throughout the development of the study.This research received financial assistance from the National Council for Scientific and Technological Develo...
PMC10345782
References
PMC10345782
Background
CHOLINE DEFICIENCY, CYSTIC FIBROSIS
Choline deficiency leads to pathologies particularly of the liver, brain and lung. Adequate supply is important for preterm infants and patients with cystic fibrosis. We analysed the assimilation of four different enterally administered deuterium-labelled (D9-) choline supplements in adults.
PMC10195734
Methods
Prospective randomised cross-over study (11/2020–1/2022) in six healthy men, receiving four single doses of 2.7 mg/kg D9-choline equivalent each in the form of D9-choline chloride, D9-phosphorylcholine, D9-alpha-glycerophosphocholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-glycero-3-phosphoryl-choline (D9-POPC), in randomi...
PMC10195734
Results
Maximum D9-choline and D9-betaine concentrations were reached latest after D9-POPC administration versus other components. D9-POPC and D9-phosphorylcholine resulted in lower D9-trimethylamine (D9-TMAO) formation. The AUCs (0-7d) of plasma D9-PC concentration showed highest values after administration of D9-POPC. D9-POP...
PMC10195734
Conclusion
There was a delayed increase in plasma D9-choline and D9-betaine after D9-POPC administration, with no differences in AUC over time. D9-POPC resulted in a higher AUC of D9-PC and virtually absent D9-TMAO levels. D9-POPC is remodelled according to enterocytic fatty acid availability. D9-POPC seems best suited as choline...
PMC10195734
Study registration
This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498.
PMC10195734
Supplementary Information
The online version contains supplementary material available at 10.1007/s00394-023-03121-z.
PMC10195734
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC10195734
Introduction
breast milk
CYSTIC FIBROSIS, CHOLINE DEFICIENCY
Nutritional supply of choline as an essential nutrient is often not sufficient [In preterm infants, plasma levels of choline rapidly fall by 50% after birth, leading to an unphysiological decrease during a time of exponential growth and choline requirements [The liver’s choline homeostasis is important to secrete bile ...
PMC10195734
Methods
This is a randomised cross-over study, carried out at the Department of Neonatology, Tübingen University Hospital, Germany. Six healthy adult men were recruited and studied between November 2020 and January 2022. The Institutional Review Board (project number 322/2019BO1) approved the protocol, and written informed con...
PMC10195734
Inclusion criteria
chronic diseases, acute illness, thyroid diseases, alcohol abuse, diabetes
PANCREAS INSUFFICIENCY, CHRONIC DISEASES, THYROID DISEASES, METABOLIC SYNDROME, DIABETES
Test persons had to be male and at least 18 years old.Exclusion criteria were alcohol abuse, acute illness, chronic diseases (like diabetes, metabolic syndrome, thyroid diseases, pancreas insufficiency), intake of choline containing nutritional supplements or missing consent.
PMC10195734
Supplements
D9-phosphorylcholine chloride
The deuterium-labelled (D9) analogues choline-d9 chloride [N,N,N-trimethyl-d9] (D9-choline chloride), D9-phosphorylcholine chloride, calcium salt (D9-phosphorylcholine), D9-alpha-glycerophosphorylcholine (D9-GPC) and D9-1-palmitoyl-2-oleoyl-glycero-3-phosphorylcholine (D9-POPC) were from EQ Laboratories GmbH (Augsburg,...
PMC10195734
Study schedule
STERILE, BLOOD
Directly prior to use, substances were dissolved/emulsified in 10 ml sterile water and topped up with 250 ml apple spritzer. Test subjects had to ingest in a randomised sequence at least 6 weeks (w) apart D9-choline metabolite for wash out.D9-choline chloride (3.6 mg/kg),D9-phosphorylcholine chloride (6.4 mg/kg),D9-alp...
PMC10195734
Chemical analysis
The analyses of deuterium-labelled choline and its metabolites were performed with electrospray ionisation tandem mass spectrometry (ESI–MS/MS) as previously described [
PMC10195734
D9-choline and its water-soluble downstream metabolites
Figure Plasma kinetics of D9-choline (By contrast, ingestion of D9-POPC resulted in delayed (Similarly, the kinetics and maximum concentrations of D9-betaine were different in response to D9-POPC compared to water-soluble compounds (Fig. Finally, the concentrations of D6-dimethylglycine (D6-DMG), the demethylation prod...
PMC10195734
D9-TMAO
D9-TMAO was absent in response to both D9-POPC and D9-phosphocholine ingestion, but was detected after D9-choline chloride and D9-GPC, with a tendency to a later increase after D9-GPC (Fig. 
PMC10195734
D9-choline-labelled phospholipids in response to different D9-choline compounds
As demonstrated in Fig. Plasma kinetics of the sum of D9-labelled phosphatidylcholine (D9-PC) (
PMC10195734
Differential D9-PC metabolism in response to D9-POPC compared to water-soluble D9-choline supplements
To differentially address the metabolism of fatty acids of PC in response to supplements, D9-PC was differentiated into sub-groups containing different unsaturated fatty acid residues [Plasma concentrations of D9-PC sub-groups in response to deuterium-labelled (D9-) choline supplements. D9-PC molecular species were sub...
PMC10195734
D3-PC from the PEMT pathway
To estimate the use of different D9-choline supplements for their contribution to methyl group metabolism and PC synthesis via PE methylation to form PC via the PEMT pathway, we investigated the plasma concentrations of D3-PC in response to D9-choline supplements. In this pathway, (D9-)betaine from (D9-)choline oxidati...
PMC10195734
Discussion
Choline has been defined as an essential nutrient, with daily adequate intake (AI) values for healthy adult men of 550 mg according to NAM [All water-soluble supplements rapidly and similarly increased D9-choline and D9-betaine plasma levels, with maximum concentrations achieved at 0.5–1 h. This is consistent with the ...
PMC10195734
Plasma D9-PC and D3-PC metabolism in response to D9-choline supplements
PC is the major carrier for the plasma transport of long-chain polyunsaturated fatty acids (LC-PUFA), mainly arachidonic (ARA) and docosahexaenoic acid (DHA) to organs, via lipoproteins [In general, the formation of betaine, and its D9-enrichment correlated with the plasma concentrations of D3-PC (see supplementary Fig...
PMC10195734
Differential kinetics of plasma D9-PC in response to D9-choline supplements
Administration of water-soluble D9-choline compounds resulted in an increase of plasma D9-PC that showed uniform peak concentrations at 24-33 h, and a plasma half-life of 2-3d as previously demonstrated after both enteral and parenteral D9-choline chloride administration [Such fatty acid specificity is consistent with ...
PMC10195734
Impact of different choline supplements on endogenous PC synthesis by PEMT
Our data show that, in response to (D9-PO)PC, the plasma concentrations of free (D9-)choline and (D9-)betaine are decreased but their hepatic use for the synthesis of (D3-)methionine as a methyl donor and (D3-)PC synthesis from PE via the PEMT pathway is not decreased. Hence, hepatic secretion of VLDL, where both PC sy...
PMC10195734
Potential consequences of choline supplementation via PC instead of water-soluble components
MINOR
The assimilation of D9-POPC, via cleavage to D9-lyso-PC, preferential small intestinal re-acylation to D9-PC and chylomicron assembly (see above), contrasted the hepatic D9-choline, -betaine, -PC and -VLDL metabolism as represented by the other D9-choline supplements. Although D9-POPC belongs to the D9-C18:1-PC subgrou...
PMC10195734
Formation of (D9-)TMAO in response to (D9-)choline supplements
In addition to the efficacy of a choline supplement, safety is paramount. Therefore, we also investigated the concentration of D9-TMAO, the hepatic oxidation product of D9-TMA that is a bacterial D9-choline degradation product. TMAO has been described as a cardiovascular risk factor [Differences in absorption may also ...
PMC10195734
Conclusion
There was a retarded increase in plasma D9-choline and D9-betaine as well as higher peak concentrations and AUCs of D9-PC and virtually absent D9-TMAO formation after D9-POPC and D9-phosphocholine administration. The use of (D9-PO)PC as a choline supplement for preferential enterocytic synthesis of polyunsaturated (D9-...
PMC10195734
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (PPTX 195 KB)
PMC10195734
Abbreviations
Adequate intakeCystic fibrosisEthylenediaminetetraacetateEuropean Food Safety AuthorityUS-Food and Drug AdministrationAlpha-glycerophosphocholineGenerally recognised as safeNational Academy of Medicine of the USAPhosphatidylcholine(D9-)1-palmitoyl-2-oleoyl-PC(D9-choline labelled)PC containing an oleic acid residue(D9-c...
PMC10195734
Authors’ contributions
MM, ARF
ARF
WB and AF conceptualised the study. KB, WB and AF drafted the manuscript. MM and KB coordinated and supervised the study, contributed to sample collection and assessment of clinical data and approved the final manuscript as submitted. WB developed the analytical techniques, supervised the analyses, contributed to sampl...
PMC10195734
Funding
Open Access funding enabled and organized by Projekt DEAL. This investigator-initiated trial was partly funded by a research grant from HiPP-Werk Georg Hipp OHG, a manufacturer of infant formula and partly funded by a research grant from the Ministry of Economy of the State of Baden-Württemberg (AsphyxDx, Az. 35-4223.1...
PMC10195734
Declarations
PMC10195734
Conflict of interest
The authors declare that they have no conflict of interest to disclose. Trial Registration: This trial was registered at
PMC10195734
Ethical standards
The study has been approved by the institutional ethics committee and performed in accordance with the ethical standards laid down in the 64th WMA General Assembly, Fortalezza, Brazil, October 2013. Test persons gave their written informed consent prior to inclusion in the study.
PMC10195734
References
PMC10195734
ABSTRACT
headaches, mild/moderate, hypoparathyroidism, PaTHway, hypocalcemia
HYPOCALCEMIA, SECONDARY, HYPOPARATHYROIDISM, ADVERSE EVENTS
Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double‐blind, placebo‐controlled, 26‐week, phase ...
PMC10099823
Introduction
hypoparathyroidism, endocrine disease, Hypoparathyroidism
HYPOCALCEMIA, HYPOPARATHYROIDISM, ENDOCRINE DISEASE, HYPOPARATHYROIDISM
Hypoparathyroidism is an endocrine disease caused by insufficient or absent production of parathyroid hormone (PTH) with multiorgan involvement. Under normal physiological conditions, PTH and its downstream hormone calcitriol are the primary regulators of calcium and phosphate and act on the bone, kidney, and intestine...
PMC10099823
Materials and Methods
PMC10099823
Trial design
PaTHway
HYPOPARATHYROIDISM
PaTHway is a phase 3, multicenter (North America and Europe), randomized, double‐blind, placebo‐controlled, parallel‐group, 26‐week trial with an open‐label extension of 156 weeks that evaluated the efficacy, safety, and tolerability of once‐daily TransCon PTH as PTH replacement therapy in individuals with hypoparathyr...
PMC10099823
Participants
μg/d, hypoparathyroidism, idiopathic etiologies
HYPOPARATHYROIDISM
Eligible participants included men and nonpregnant women (≥18 years of age) with chronic hypoparathyroidism of postsurgical, autoimmune, genetic, or idiopathic etiologies for a duration of at least 26 weeks. Participants must have been treated with calcitriol ≥0.5 μg/d or alfacalcidol ≥1.0 μg/d in addition to elemental...
PMC10099823
Trial protocol
hypoparathyroidism
HYPOPARATHYROIDISM
Once enrolled, participants were randomized 3:1 into two treatment groups: TransCon PTH 18 μg PTH(1‐34)/d or placebo (excipient solution) mimicking 18 μg/d, both co‐administered with conventional therapy (active vitamin D and elemental calcium). Randomization was stratified by etiology of hypoparathyroidism (postsurgic...
PMC10099823
Efficacy assessments
The composite primary efficacy outcome of the PaTHway trial was the proportion of participants at week 26 who achieved albumin‐adjusted serum calcium in the normal range (8.3–10.6 mg/dL [2.07–2.64 mmol/L]), independence from active vitamin D, and independence from therapeutic doses of elemental calcium (>600 mg/d) with...
PMC10099823
Patient‐reported outcomes
pain, disability, Hypoparathyroidism
HYPOPARATHYROIDISM
At baseline and weeks 10, 20, and 26, participants completed the Hypoparathyroidism Patient Experience Scale (HPES), a psychometrically validated, disease‐specific questionnaire that includes both symptom and impact measures.Participants also completed the 36‐Item Short‐Form Health Survey (SF‐36, version 2), a 36‐item ...
PMC10099823
Safety assessments
TEAEs, hypercalcemia
ADVERSE EVENTS, EVENTS, HYPERCALCEMIA
At prespecified intervals throughout the trial, information on the use of concomitant medications was collected. Serum chemistries, hematology, and 25‐hydroxyvitamin D levels, as well as antibodies against PTH, TransCon PTH, and polyethylene glycol (PEG) were measured. Twenty‐four‐hour urine calcium excretion was also ...
PMC10099823
Statistical analysis
hypoparathyroidism
SECONDARY, HYPOPARATHYROIDISM
Sample size calculations assuming a 70% response rate for TransCon PTH and 15% for placebo for the primary composite endpoint indicated that 68 participants randomized 3:1 to active TransCon PTH versus placebo would have 99% statistical power at Data from clinical assessments were summarized using descriptive statistic...
PMC10099823
Results
PMC10099823
Participant disposition and baseline demographics
cardiac arrest
DISEASE, CARDIAC ARREST, BREAST CANCER
A total of 106 participants were screened for eligibility, and 84 were randomized to treatment (Patient disposition. A total of 106 participants were screened, and 84 met eligibility criteria, were enrolled in the trial, and randomized to treatment. Two participants randomized to TransCon PTH discontinued the trial bef...
PMC10099823
Efficacy
hypoparathyroidism, normocalcemia
HYPOPARATHYROIDISM
After 26 weeks of blinded treatment, 79% (48/61) of participants receiving TransCon PTH versus 5% (1/21) receiving placebo achieved the primary composite endpoint of independence from conventional therapy, with maintenance of normocalcemia without an increase in study drug dose in the final 4 weeks of the blinded perio...
PMC10099823
Patient‐reported outcomes
hypoparathyroidism
HYPOPARATHYROID, SECONDARY, HYPOPARATHYROIDISM
Both HPES and SF‐36 scores improved through week 26 in the TransCon PTH group. The disease‐specific HPES showed improvements in hypoparathyroidism‐related symptoms, functioning, and well‐being for participants treated with TransCon PTH. Treatment with TransCon PTH demonstrated a statistically significant improvement co...
PMC10099823
Safety
toxicity, cardiac arrest
ADVERSE EVENT, ADVERSE EVENT, CARDIAC ARREST
Mean 24‐hour urine calcium levels decreased from 392 mg/24 h at baseline to 220 mg/24 h in participants treated with TransCon PTH compared with 329 mg/24 h at baseline to 292 mg/24 h with placebo (Fig. Twenty four‐hour urine calcium with TransCon PTH treatment. Box plot of 24‐hour urine calcium. Within each box, horizo...
PMC10099823