title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Conflicts of Interest | The authors declare no conflict of interest. | PMC10001681 | ||
References | TG | Body weight (kg). Significantly different pre-vs. post-intervention at ** Body fat (%). Significantly different pre-vs. post-intervention at ** TC (mg/dL). TC, Total cholesterol; ** TG (mg/dL). TG, Triglyceride; ** LDL (mg/dL). LDL, Low-density lipoprotein; * HDL (mg/dL). HDL, High-density lipoprotein.Adiponectin. Sign... | PMC10001681 | |
Supplementary Information | Risdiplam | Risdiplam is an oral, survival of motor neuron 2 (The online version contains supplementary material available at 10.1007/s00415-023-11560-1. | PMC9897618 | |
Keywords | PMC9897618 | |||
Introduction | PMC9897618 | |||
Overview of SMA and the natural history of types 2 and 3 SMA | SMA, autosomal recessive neuromuscular disorder | SPINAL MUSCULAR ATROPHY 4 | Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by reduced levels of survival of motor neuron (SMN) protein due to homozygous deletions or loss-of-function mutations in the Patients with type 2 SMA develop symptoms between 6 and 18 months of age, achieve the ability to sit independ... | PMC9897618 |
Risdiplam overview | Risdiplam | Risdiplam (Evrysdi® [F. Hoffmann La-Roche Ltd/Genentech Inc.]) is an orally administered small molecule indicated for the treatment of patients in the USA [Risdiplam modifies | PMC9897618 | |
Overview of the SUNFISH study | risdiplam | SUNFISH (NCT02908685) [Part 1 was a dose-finding study in patients with type 2 or type 3 SMA (ambulant and non‑ambulant) to inform the dose for Part 2. In Part 1, risdiplam treatment led to a sustained increase in SMN protein in the blood, and exploratory efficacy analyses showed improvement or stabilization in motor f... | PMC9897618 | |
Methods | PMC9897618 | |||
Study oversight | ADVERSE EVENTS | This trial was approved by an ethics committee at each study site and was conducted in accordance with Good Clinical Practice guidelines and the World Medical Association Declaration of Helsinki. Written informed consent was provided by the patient or by parents/caregivers. The sponsor, F. Hoffmann-La Roche Ltd, provid... | PMC9897618 | |
Patients and study procedures | non-ambulant | Eligible patients were non-ambulant and aged 2–25 years, with a genetically confirmed diagnosis of 5q-autosomal recessive SMA and clinical symptoms attributable to type 2 or type 3 SMA. Patients were excluded from the study if they had received treatment with an | PMC9897618 | |
Study design and outcomes | risdiplam | Patients were stratified by age (2–5, 6–11, 12–17, and 18–25 years) and randomized 2:1 with concealed allocation to receive either risdiplam or placebo daily for 12 months. The risdiplam dose was 0.25 mg/kg for patients weighing < 20 kg, and 5 mg for patients weighing ≥ 20 kg [The 24-month exploratory objectives and ou... | PMC9897618 | |
Statistical methods | non-ambulant, risdiplam, scoliosis | REGRESSION, DISEASE CHARACTERISTIC, SCOLIOSIS | Exploratory efficacy analyses were conducted based on the all-exposure-to-risdiplam treatment period (the treatment period after receiving the first dose of risdiplam). Randomized patients who did not receive risdiplam treatment were not included in the exploratory efficacy analyses; this condition applied to one patie... | PMC9897618 |
Results | PMC9897618 | |||
Patients | risdiplam | A total of 180 patients were enrolled in SUNFISH Part 2 and were randomized to receive risdiplam (After month 12, all patients received risdiplam. A total of 176 patients entered the open-label treatment period (defined as months 12–24 in the study). Motor function scores from the 59 patients who switched from placebo ... | PMC9897618 | |
Motor function | PMC9897618 | |||
RULM | risdiplam | At month 24, the mean change from baseline (95% CI) in RULM total score was 2.8 (1.9–3.6) (Table Change in RULM and HFMSE total score from baseline in patients receiving risdiplam for up to 24 months and those who previously received placebo up to study month 12. | PMC9897618 | |
HFMSE | At month 24, the mean change from baseline (95% CI) in HFMSE total score was 2.2 (1.1–3.2) (Table | PMC9897618 | ||
Respiratory function | PMC9897618 | |||
FVC | risdiplam | FVC was assessed in patients aged 6–25 years at screening. In patients who received risdiplam for 24 months, the mean change from baseline in the best percentage-predicted FVC (95% CI) was – 7.8% (– 11.6 to – 3.9%) after 24 months of risdiplam treatment (Table | PMC9897618 | |
Caregiver- and patient-reported independence | PMC9897618 | |||
SMAIS-ULM | risdiplam | In patients who received risdiplam for 24 months, the mean change from baseline (95% CI) in the caregiver-reported SMAIS-ULM total score was 2.7 (1.7–3.7) at month 24 (Table Change in caregiver- and patient-reported SMAIS upper limb total score from baseline in patients receiving risdiplam for up to 24 months and those... | PMC9897618 | |
Discussion | DISEASE | The natural history of types 2 and 3 SMA involves progression of disease and continued loss of function [ | PMC9897618 | |
Motor function and independence | Risdiplam, non-ambulant, risdiplam, prolonged disease, later-onset SMA | DISEASE | Risdiplam treatment in a clinically heterogeneous population of children, teenagers, and adults with later-onset SMA and varying disease duration resulted in continued stabilization or improvement in motor function. Although analyses are exploratory, overall, the gains in motor function after 12 months of risdiplam tre... | PMC9897618 |
Respiratory function | BEST | Best percentage-predicted FVC in this population declined at a rate consistent with natural history findings [ | PMC9897618 | |
Safety | toxicity, pneumonia, risdiplam, retinal toxicity | PNEUMONIA, EYE DISORDERS | The safety profile after 24 months of treatment was consistent with the safety results after 12 months of treatment (Table Initial observations in the double-blind period showed a slightly higher incidence of serious pneumonia in patients in the risdiplam arm (8%) compared with the placebo arm (2%). However, the incide... | PMC9897618 |
Conclusion | risdiplam, Risdiplam, later-onset SMA, upper limb motor function | DISEASE | Risdiplam treatment in a broad and clinically heterogeneous patient population of children, teenagers, and adults with later-onset SMA and varying disease duration resulted in continued clinically relevant gains in motor function. This was demonstrated by improvements (32% of patients) and stabilization (58% of patient... | PMC9897618 |
Supplementary Information | SPINAL MUSCULAR ATROPHY 1 | Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 49 kb)The authors would like to thank all individuals enrolled in the risdiplam studies, their families, and the site staff involved. The authors would also like to thank the Spinal Muscular Atrophy Foundation and PTC Therapeutics for ... | PMC9897618 | |
Author contributions | CM | CV, KG, HK, CM, WYY, and PF contributed to the study conception and design. Data were collected by MO, ND, ESM, AN, KS, CV, GB, NG, JK, AK-P, LS, and EM. Analysis was performed by ND, AN, KG, TM, WYY, and PF. Interpretation was performed by all authors. All authors reviewed and edited drafts of the manuscript and appro... | PMC9897618 | |
Funding | This study is sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Medical writing and editing support were funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland in accordance with Good Publication Practice (GPP3) guidelines ( | PMC9897618 | ||
Data availability | For eligible studies, qualified researchers may request access to individual patient level clinical data through a data request platform. At the time of writing this request platform is Vivli. | PMC9897618 | ||
Declarations | PMC9897618 | |||
Conflicts of interest | CM, AveXis/Novartis | MO reports grants from F. Hoffmann-La Roche Ltd during the conduct of the study and has received grants as a clinical trial investigator from Biogen. JWD has received fees for serving on scientific advisory boards from Biogen, Novartis, Sarepta Therapeutics, and Avidity; has received consulting fees from Affinia Therap... | PMC9897618 | |
Ethical approval | This trial was approved by an ethics committee at each study site and was conducted in accordance with Good Clinical Practice guidelines and with the World Medical Association Declaration of Helsinki. | PMC9897618 | ||
Informed consent | Written informed consent was provided by the patient or by the patients’ legally authorized representative before participating in the study. | PMC9897618 | ||
References | PMC9897618 | |||
Subject terms | stress | AIDS | Tobacco use is the leading cause of preventable mortality worldwide. Since current smoking cessation aids show only modest efficacy, new interventions are needed. Given the evidence that stress is a potent trigger for smoking, the present randomized clinical trial tested whether stress could augment the effects of a me... | PMC9750979 |
Introduction | death, smoking behaviors, anxiety | DISORDERS | Tobacco use is the primary cause of preventable death worldwide [A fundamental feature of smoking is the learned associations between smoking behaviors and cigarette-related cues [In the past two decades, memory reconsolidation blockade interventions have shown promise as treatments for stress and anxiety related disor... | PMC9750979 |
Methods | PMC9750979 | |||
Participants | Non-treatment seeking smokers were recruited through online advertisements, flyers posted around Montreal, and word-of-mouth. Study eligibility was determined from telephone interviews using the Fagerström Test for Cigarette Dependence (FTCD) [ | PMC9750979 | ||
Procedures | This randomized clinical trial took place between February 2019 and January 2020. The study comprised five in-person visits, including baseline, intervention, and three test sessions given 24 h, two weeks and six weeks post-intervention (Fig. | PMC9750979 | ||
Experimental design and timeline. | During the initial assessment and test sessions 1, 2 and 3, a novel smoking-related video was shown to participants. Physiological measures (heart rate (HR) and skin conductance (SC)) were collected prior to and during the last minute of each video presentation. During these same visits, blood pressure (BP) and self-re... | PMC9750979 | ||
Baseline | During the first study visit, participants provided demographic information, including age, sex, ethnicity, level of education, employment status, and history of cigarette use. They completed the Contemplation Ladder [ | PMC9750979 | ||
Intervention | Prior to the baseline session, participants were randomized to one of four conditions (phase 1) using a 2 × 2 factorial design: (1) stress task and smoking cue, (2) stress task and neutral cue, (3) control task and smoking cue, or (4) control task and neutral cue. The stress task was the Montreal Imaging Stress Test (M... | PMC9750979 | ||
Test sessions 1, 2 and 3 | Participants returned to the laboratory for cue reactivity test sessions 24 h, two weeks, and six weeks following the intervention. During each of these sessions, SC, HR and BP were measured, and the CWS-21, Contemplation Ladder, FTCD (for tests 2 and 3), TCQ-SF and QSU-Brief were administered. Participants then viewed... | PMC9750979 | ||
Statistical analyses | SPSS 26.0.0.1 (Chicago, IL) was used for all statistical analyses. Preliminary analyses indicated less than 1% missing data on all variables. Multiple imputation was used to impute missing scores. Chi square tests and analyses of variance (ANOVAs) were used to examine group differences in study characteristics at basel... | PMC9750979 | ||
Results | PMC9750979 | |||
Participant characteristics | Seventy-six volunteers were deemed eligible for the study (Fig. | PMC9750979 | ||
Experimental manipulation check | Since this was the first time stress and smoking cues were combined in a memory updating procedure, we initially examined whether they elicited their expected effects during phase 1 of the intervention session. As hypothesized, the stress task yielded the predicted effects within the smoking cue groups ( | PMC9750979 | ||
Responses during the intervention | PMC9750979 | |||
Phase 1 | When comparing scores obtained immediately pre- and post-phase 1, there were main effects of time reflecting anticipated decreases in HR ( | PMC9750979 | ||
The stress task-induced psychophysiological and craving responses during the behavioral intervention. | During phase 1 ( | PMC9750979 | ||
Phase 2 | Across groups, the extinction procedure significantly increased SC ( | PMC9750979 | ||
Cue reactivity assessments | PMC9750979 | |||
Baseline | As expected, exposure to a smoking-related video led to a main effect of time revealing significant increases in craving (QSU-Brief: | PMC9750979 | ||
Tests 1, 2 and 3 | Across groups, at each test session, exposure to a new smoking-related video led to increased SC response (all | PMC9750979 | ||
Across sessions | Across sessions, physiological responses to the video cues became less pronounced as shown by decreases in SC (( | PMC9750979 | ||
Smoking behavior | Over the period of the study, participants decreased their cigarette use as reflected by a significant main effect of session ( | PMC9750979 | ||
Predictors of decreased cigarette use | When participants from all groups were combined, higher systolic BP values following phase 1 of the intervention predicted larger decreases in cigarette use at test session 3 ( | PMC9750979 | ||
Discussion | The present study tested whether a laboratory stressor could augment the ability of a memory updating procedure to decrease cigarette use. While our predictions for the cue-based intervention were not supported, two hypotheses about the stressor were. First, during phase 1 of the intervention, greater craving and physi... | PMC9750979 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41386-022-01455-6. | PMC9750979 | ||
Acknowledgements | The authors would like to thank Rhonda Amsel for valuable statistical advice and Elena Pérez Gómez for assembling and editing the smoking and neutral video cues. We are also grateful to the large team of undergraduate students who assisted with screening and administrative tasks. | PMC9750979 | ||
Author contributions | AB, KG and ML had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: AB, KG, KN, ML. Acquisition, analysis, or interpretation of data: All authors. Statistical analysis: AB, KG, ML. Drafting of the manuscript... | PMC9750979 | ||
Funding | JP | This research was funded by a James McGill Professor Research Award to KN and Canadian Institutes of Health Research operating funds to KN and ML (MOP-211696) and JP and KN (PJT-148728). The funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; prep... | PMC9750979 | |
Competing interests | The authors declare no competing interests. | PMC9750979 | ||
References | PMC9750979 | |||
Abstract | PMC10240182 | |||
Background | hair loss, FAGA | HAIR LOSS, ANDROGENIC ALOPECIA, TELOGEN EFFLUVIUM | Oral supplementation with some amino acids (like methionine, taurine, and cysteine) could be useful in subjects with hair loss conditions such as androgenic alopecia (AGA or FAGA) or telogen effluvium (TE). Hydrolysed collagen (HC) oral supplementation has demonstrated to have beneficial effects on nail and skin health... | PMC10240182 |
Study aims | hair loss | HAIR LOSS | To evaluate and compare the efficacy and tolerability of an oral supplementation based on HC and amino acids in subjects with hair loss due to AGA/FAGA or chronic TE in combination with drug treatments in comparison with drug treatments alone. | PMC10240182 |
Methods and subjects | ±, hair loss | HAIR LOSS, LUDWIG | In a prospective, 12‐week, randomized, assessor‐blinded controlled trial 83 subjects (mean age 41 ± 16 years; 26 men and 57 women) were enrolled in the study. Fifty‐nine subjects suffered from AGA/FAGA (Hamilton I‐VA, Ludwig I‐1, II‐2) and 24 from chronic TE. Subjects were randomized to oral supplementation (1 tablet d... | PMC10240182 |
Results | ± | GROUP B | Seventy‐six participants (91.6%) completed the 12‐week study period. The GAS score at week 6 was 0.5 ± 0.2 in group A and 0.0 ± 0.1 in Group B ( | PMC10240182 |
Conclusion | An oral supplement containing hydrolysed fish‐origin collagen, taurine, cysteine, methionine, iron, and selenium has demonstrated to improve the clinical efficacy of specific anti‐hair loss treatments in subjects with AGA/FAGA or chronic TE.
| PMC10240182 | ||
INTRODUCTION | hair loss, alopecia, FAGA | HAIR LOSS, ALOPECIA, TELOGEN EFFLUVIUM, HAIR LOSS | Hair loss can be classified in several forms including male‐ or female‐androgenetic alopecia (AGA and FAGA, respectively), and telogen effluvium (TE). AGA is one of the most frequent hair loss causes, | PMC10240182 |
STUDY AIM | hair loss | HAIR LOSS | The aim of this study was to evaluate the efficacy and tolerability of an oral supplementation (based on HC, amino acids, and micronutrients) in combination with drug treatments (e.g., minoxidil or finasteride) in subjects with hair loss due to AGA/FAGA or TE in comparison with drug treatments alone. | PMC10240182 |
SUBJECTS AND METHODS | PMC10240182 | |||
Population and study design | mycosis, alopecia areata, ±, psoriasis, Hair loss, allergies, FAGA | HAIR THINNING, MYCOSIS, ALOPECIA AREATA, PSORIASIS, MAY, THINNING HAIR, IRON DEFICIENCY, HAIR LOSS, ALLERGIES, SEBORRHEIC DERMATITIS, LUDWIG | Between May 2022 and November 2022, 83 subjects with AGA, FAGA or chronic TE were assessed and screened for inclusion in the trial. Hair loss condition was confirmed by physical examination performed by a dermatologist that assigned a clinical diagnosis of AGA or chronic TE. AGA was diagnosed using the Hamilton or Ludw... | PMC10240182 |
Study outcomes | The primary efficacy endpoint was evaluated in an assessor‐blinded fashion after 6 (facultative visit) and 12 weeks by a panel of six dermatologist (GFM‐O‐Trial Investigator Group) through the global assessment score (GAS), a 7‐point score from −3 (severe worsening) to +3 (excellent improvement) performed using standar... | PMC10240182 | ||
Statistical analysis and sample size calculation | A total of 83 participants were enrolled and randomized in two groups. Sample size calculation was performed considering the data of Panchaprateep and Lueangarun, | PMC10240182 | ||
RESULTS | hair loss, FAGA | MAY, HAIR LOSS | Between May 2022 and November 2022, 83 subjects with AGA, FAGA or chronic TE were assessed and screened for inclusion in the trial. Demographics and baseline characteristic were similar between groups (Table Demographics and baseline characteristics.Seventy‐six participants completed the trial (91.6%), and seven subjec... | PMC10240182 |
Primary endpoint | ± | The GAS was evaluated in an assessor blinded fashion after 6 (facultative visit) and 12 weeks by the investigators using a 7‐point score from −3 (severe worsening) to +3 (excellent improvement). After 6 weeks, the mean GAS increased only in Group A (0.5 ± 0.2 in Group A and 0.0 ± 0.1 in group B). After 12 weeks both th... | PMC10240182 | |
Secondary endpoints | ±, hair loss, gastro‐intestinal adverse | HAIR LOSS | Global clinical efficacy was evaluated in an open fashion both by investigators and patients trough questionnaires converted in a 5‐point score scale. The mean global clinical efficacy was higher in group A both for investigators (differences between means 0.33 ± 0.14, 95% CI: 0.05–0.62) and patients (differences betwe... | PMC10240182 |
DISCUSSION | anti‐hair loss | BLIND, HAIR LOSS | Hair loss is a common problem that affects up to 50 percent of men and women.Some limitations should be considered in evaluating our results. First, the two arms of the study were slightly unbalanced (48 subjects in group A and 35 subjects in group B). This could be explained by the randomization conducted using a bloc... | PMC10240182 |
CONCLUSIONS | hair loss disorders | This clinical trial demonstrated that the tested oral supplement, containing hydrolysed fish‐origin collagen, taurine, cysteine, methionine, iron and selenium was able to improve the clinical efficacy of specific anti‐hair loss treatments in subjects with hair loss disorders such as AGA/FAGA or TE. | PMC10240182 | |
CONFLICT OF INTEREST STATEMENT | MM | MM and FC are employees of Difa Cooper Catabria Labs that commercialized the food supplement. The authors report no other conflict of interest in this work. | PMC10240182 | |
ETHICS STATEMENT | All participants provided written informed consent and a photo consent statement before starting the study. | PMC10240182 | ||
DATA AVAILABILITY STATEMENT | SAID | The author has provided the required Data Availability Statement, and if applicable, included functional and accurate links to said data therein. | PMC10240182 | |
REFERENCES | PMC10240182 | |||
Subject terms | neurodevelopmental disorder, Rett syndrome | RETT SYNDROME | Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine–proline–glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study (Results from the LAVENDER... | PMC10287558 |
Main | seizures, hand stereotypies, loss of verbal communication, neurodevelopmental disorder, Rett syndrome, RTT | RETT SYNDROME | Rett syndrome (RTT) is a rare, genetic neurodevelopmental disorder characterized by loss of verbal communication with limited nonverbal skills, loss of fine and gross motor function (including purposeful hand use), behavioral issues, seizures, hand stereotypies and gastrointestinal problemsRTT primarily affects females... | PMC10287558 |
Results | PMC10287558 | |||
Demographic and baseline characteristics | Enrollment occurred between 29 October 2019 and 28 October 2021, with 208 participants screened and 187 participants randomized to trofinetide ( | PMC10287558 | ||
Primary efficacy outcomes | The mean (s.e.m.) change from baseline to week 12 in the RSBQ total score was −5.1 (0.99) and −1.7 (0.98) in the trofinetide and placebo groups, respectively. Based on the mixed-effect model for repeated measure (MMRM) analysis, the LSM (s.e.m.) change from baseline to week 12 in the RSBQ total score was statistically ... | PMC10287558 | ||
Key secondary efficacy outcome | The mean (s.e.m.) change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant–Toddler Checklist (CSBS-DP-IT) Social Composite score was −0.1 (0.28) and −1.1 (0.28) in the trofinetide and placebo groups, respectively. MMRM analysis showed a statistically significant dif... | PMC10287558 | ||
Secondary efficacy outcomes | SECONDARY | Results for the other secondary endpoints are shown in Extended Data Table | PMC10287558 | |
Post hoc efficacy analyses | diarrhea | The results for the coprimary endpoints were comparable irrespective of diarrhea TEAE status (Extended Data Table | PMC10287558 | |
Discussion | diarrhea, antiseizure, TEAEs, vomiting, constipation, neurodevelopmental disorders, RTT | SECONDARY, RARE DISEASE, SYNDROME, PATHOPHYSIOLOGY | In this phase 3 study in a large cohort of girls and women 5–20 years of age with RTT, trofinetide demonstrated a statistically significant improvement over placebo for both the coprimary and key secondary efficacy endpoints. Treatment with trofinetide improved key symptoms of the syndrome from the perspective of both ... | PMC10287558 |
Methods | PMC10287558 | |||
Study design | The study design and methods have been published previouslyA single dose level of trofinetide was tested using weight-based dosing to achieve the target exposure identified based on the results of the previous phase 2 studyThe study included a screening period of ≤3 weeks, a 12-week double-blind treatment period and a ... | PMC10287558 | ||
Study population | RTT | Girls and women 5–20 years of age with RTT, a score of 10–36 on the RTT Clinical Severity Scale | PMC10287558 | |
Intervention | Trofinetide (200 mg ml | PMC10287558 |
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