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International Journal of Medical... 2023B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide... (Randomized Controlled Trial)
Randomized Controlled Trial
A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial.
B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide energy, each B vitamin acts as a cofactor in energy metabolism processes. Based on the evidence presented above, we hypothesized that a 28-day supplementation of vitamin B would enhance physical performance and reduce physical fatigue. The objective of this study was to evaluate the anti-fatigue effect of vitamin B supplementation, specifically vitamin B1, B2, B6, and B12, and its potential to improve exercise performance. We employed a randomized double-blind crossover design with a 28-day supplementation period. Sixteen male and sixteen female subjects, aged 20-30 years, were divided into two groups: the placebo group (n=16, equal gender distribution) and the Ex PLUS group (n=16, equal gender distribution). The participants received either placebo or Ex PLUS (one tablet per day) for 28 consecutive days. Following the intervention, there was a 14-day wash-out period during which the subjects did not receive any further interventions. After supplementation with Ex PLUS, we found a significant increase in the running time by 1.26-fold ( 0.05) to exhaustion compared to that before supplementation and that in the placebo group. In addition, the Ex PLUS supplementation group presented significantly reduced blood lactate and blood ammonia concentrations during exercise and at rest after exercise compared with placebo ( < 0.05). In conclusion, 28 consecutive days of vitamin B complex (Ex PLUS) supplementation significantly improved exercise endurance performance and reduced exercise fatigue biochemical metabolites in not athletes. In addition, it does not cause adverse effects in humans when taken at appropriate doses.
Topics: Humans; Male; Female; Vitamin B Complex; Dietary Supplements; Folic Acid; Health Status; Fatigue; Double-Blind Method
PubMed: 37786445
DOI: 10.7150/ijms.86738 -
Clinical Gastroenterology and... Jul 2023GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC).
METHODS
GLIMMER was a Phase 2b, multicenter, randomized, parallel-group study in adults with PBC and moderate-to-severe pruritus (≥4 on 0-10 numerical rating scale [NRS]). After 4 weeks of single-blind placebo, patients with NRS ≥3 were randomized (3:1) to double-blind linerixibat/placebo for 12 weeks (to week 16), followed by single-blind placebo (to week 20). The primary objective was to investigate dose-related changes in mean worst daily itch (MWDI) score.
RESULTS
One hundred forty-seven patients received placebo (n = 36) or linerixibat (once daily: 20 mg, n = 16; 90 mg, n = 23; 180 mg, n = 27; twice daily: 40 mg, n = 23; 90 mg, n = 22). Linerixibat groups exhibited ≥2-point mean reductions in MWDI from baseline at week 16; however, differences from placebo were not significant. Post hoc analysis of change from baseline in monthly itch score over the treatment period (Phase 3 endpoint) showed significant differences between placebo and linerixibat 180 mg once daily (P = .0424), 40 mg twice daily (P = .0105), and 90 mg twice daily (P = .0370). A significant relationship between total daily dose and response was observed post hoc in the per protocol population (P = .0542). Consistent with mechanism of action, diarrhea was the most frequent adverse event, and incidence increased with dose.
CONCLUSIONS
Linerixibat effect on itch was not significantly different versus placebo in the primary intent-to-treat analysis but was associated with a significant dose-dependent reduction in itch in the per protocol population. A well-tolerated dose was identified for Phase 3 investigation for cholestatic pruritus in PBC.
CLINICALTRIALS
gov ID: NCT02966834.
Topics: Adult; Humans; Liver Cirrhosis, Biliary; Single-Blind Method; Treatment Outcome; Pruritus; Double-Blind Method
PubMed: 36343847
DOI: 10.1016/j.cgh.2022.10.032 -
Veterinary Anaesthesia and Analgesia Sep 2023Bedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to...
A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody.
OBJECTIVE
Bedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to support registration in the USA.
STUDY DESIGN
Randomized, double-blind, placebo-controlled, multicenter, parallel-group study.
ANIMALS
General practice client-owned dogs with osteoarthritis (n = 272).
METHODS
Dogs were block randomized 1:1 to placebo (saline, n = 137) or bedinvetmab (n = 135; 0.5-1.0 mg kg) administered subcutaneously, once monthly. The primary end point, day 28 Canine Brief Pain Inventory (CBPI) treatment success (TS), required pain severity score (PSS; 0-10) decrease ≥1 and pain interference score (PIS; 0-10) decrease ≥ 2. CBPI TS rates [and number needed to treat (NNT)], change in scores [and standardized effect size (ES)], change in quality of life (QoL) and bedinvetmab half-life were calculated.
RESULTS
Significant (p < 0.05) improvement with bedinvetmab over placebo occurred (days 28, 42, 56, 84) for CBPI TS. Of cases evaluable for day 28 CBPI TS (placebo, n = 131; bedinvetmab, n = 128), success rates were 36.6% and 47.4%, respectively (p = 0.0410) (NNT, 9.3; PSS and PIS ES, 0.3). CBPI TS increased after the second dose in both groups, plateaued for bedinvetmab at day 42 and decreased for placebo beginning day 84. Day 84 NNT (4.3), PSS (0.4) and PIS (0.5) showed continued improvement with monthly dosing. After the first dose, mean (± standard deviation) bedinvetmab half-life was 19.1 (8.3) days. Adverse events were similar between groups and not considered treatment-related. There was a significant effect of bedinvetmab versus placebo on all CBPI components (PIS, PSS, QoL).
CONCLUSIONS AND CLINICAL RELEVANCE
These results corroborated those previously reported and provide further support of safety and effectiveness of bedinvetmab (0.5-1.0 mg kg) administered subcutaneously at monthly intervals to dogs for control of osteoarthritis-related pain.
Topics: Dogs; Animals; Quality of Life; Prospective Studies; Dog Diseases; Osteoarthritis; Pain; Antibodies, Monoclonal; Double-Blind Method
PubMed: 37541934
DOI: 10.1016/j.vaa.2023.06.003 -
BMJ Open Respiratory Research Aug 2023IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550,... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in a phase II study in patients with IPF. This study design describes the subsequent pivotal phase III study of BI 1015550 in patients with IPF (FIBRONEER-IPF).
METHODS AND ANALYSIS
In this placebo-controlled, double-blind, phase III trial, patients are being randomised in a 1:1:1 ratio to receive 9 mg or 18 mg of BI 1015550 or placebo two times per day over at least 52 weeks, stratified by use of background antifibrotics (nintedanib/pirfenidone vs neither). The primary endpoint is the absolute change in FVC at week 52. The key secondary endpoint is a composite of time to first acute IPF exacerbation, hospitalisation due to respiratory cause or death over the duration of the trial.
ETHICS AND DISSEMINATION
The trial is being carried out in compliance with the ethical principles of the Declaration of Helsinki, in accordance with the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The results of the study will be disseminated at scientific congresses and in peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT05321069.
Topics: Humans; Double-Blind Method; Hospitalization; Idiopathic Pulmonary Fibrosis; Patients
PubMed: 37597969
DOI: 10.1136/bmjresp-2022-001563 -
BMJ Open Respiratory Research Sep 2023Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF).... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).
METHODS AND ANALYSIS
In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, stratified by background nintedanib use. Patients must be diagnosed with pulmonary fibrosis other than IPF that is progressive, based on predefined criteria. Patients must have forced vital capacity (FVC) ≥45% predicted and haemoglobin-corrected diffusing capacity of the lung for carbon monoxide ≥25% predicted. Patients must be receiving nintedanib for at least 12 weeks, or not receiving nintedanib for at least 8 weeks, prior to screening. Patients on stable treatment with permitted immunosuppressives (eg, methotrexate, azathioprine) may continue their treatment throughout the trial. Patients with clinically significant airway obstruction or other pulmonary abnormalities, and those using immunosuppressives that may confound FVC results (cyclophosphamide, tocilizumab, mycophenolate, rituximab) or high-dose steroids will be excluded. The primary endpoint is absolute change from baseline in FVC (mL) at week 52. The key secondary endpoint is time to the first occurrence of any acute ILD exacerbation, hospitalisation for respiratory cause or death, over the duration of the trial.
ETHICS AND DISSEMINATION
The trial is being carried out in accordance with the ethical principles of the Declaration of Helsinki, the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The study results will be disseminated at scientific congresses and in peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT05321082.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Double-Blind Method; Immunosuppressive Agents; Patients
PubMed: 37709661
DOI: 10.1136/bmjresp-2022-001580 -
Psychiatry Research Sep 2023PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD.
METHODS
A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks.
RESULTS
133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC.
CONCLUSION
This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial.
TRIAL REGISTRATION
ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.
Topics: Adult; Humans; Acetylcysteine; Stress Disorders, Post-Traumatic; Double-Blind Method; Treatment Outcome
PubMed: 37540942
DOI: 10.1016/j.psychres.2023.115398 -
Advances in Therapy Jan 2024Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study.
INTRODUCTION
Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with poor quality of life, and high socioeconomic impact. The treatments for sleep disturbances include melatonin and over-the-counter medicines like diphenhydramine and doxylamine, all of which have negative side effects. Valerian (Valeriana officinalis L.) is a traditional herb and the most preferred alternate sleep solution to manage sleep complaints.
METHODS
Eighty adult subjects with sleep complaints were randomized in 1:1 ratio to receive either V. officinalis extract (VE) or placebo for 8 weeks in a double-blind, placebo-controlled, parallel, clinical study. Primary efficacy endpoints included the Pittsburgh Sleep Quality Index (PSQI) and sleep latency using wrist actigraphy (WA), as well as a number of secondary endpoints, including sleep parameters such as actual sleep time and sleep efficiency using WA, the Epworth Sleepiness Scale (ESS), the Beck Anxiety Inventory (BAI), the Visual Analogue Scale (VAS) for the feeling of waking up refreshed, and a tertiary endpoint of sleep parameters using polysomnography (PSG) in a subset of 20 subjects per group. Safety parameters included physical examination, vital sign measurements, hematology, and clinical chemistry tests. Adverse events and serious adverse events were monitored throughout the study period.
RESULTS
Seventy-two subjects (35 and 37 subjects in the placebo and VE groups, respectively) completed the study and were included in the efficacy assessments. On Days 14, 28, and 56, the PSQI Total Score in the VE group decreased significantly (p < 0.05) compared to the placebo group. Further, the VE group showed significant improvements (p < 0.05) in sleep latency and actual sleep time on Days 3, 14, 28, and 56, and sleep efficiency on Days 14, 28, and 56, as evaluated by WA. There was a decrease (p < 0.05) in anxiety (BAI) on Days 14, 28, and 56, daytime drowsiness (ESS) on Days 28 and 56, and an increased feeling of waking up refreshed (VAS) on Days 28 and 56 compared to placebo. PSG results carried out in subset of subjects revealed significant improvements (p < 0.05) in total sleep time, sleep latency, and sleep efficiency on Day 56 in the VE group compared to the placebo group. No safety concerns were observed throughout the study.
CONCLUSION
VE supplementation significantly improved various subjective and objective parameters of sleep in young subjects with mild insomnia symptoms, such as overall sleep quality, sleep latency, sleep efficiency, and total sleep time. We also observed decreased anxiety and daytime sleepiness, and improved feeling of being refreshed after waking up with VE supplementation. VE was found to be safe and well tolerated throughout the study.
TRIAL REGISTRATION
Clinical Trials Registry of India: CTRI/2022/05/042818.
Topics: Adult; Humans; Valerian; Sleep Quality; Quality of Life; Sleep; Sleep Initiation and Maintenance Disorders; Plant Extracts; Research Subjects; Double-Blind Method; Treatment Outcome
PubMed: 37899385
DOI: 10.1007/s12325-023-02708-6 -
Nature Communications Oct 2023Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled,... (Randomized Controlled Trial)
Randomized Controlled Trial
Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.
Topics: Humans; Diarrhea; Double-Blind Method; Non-alcoholic Fatty Liver Disease; Treatment Outcome
PubMed: 37828034
DOI: 10.1038/s41467-023-42162-0 -
Nutrients Jul 2023Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether... (Randomized Controlled Trial)
Randomized Controlled Trial
Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether ingesting a liposomal multivitamin and mineral supplement (MVM) differentially affects the appearance and/or clearance of vitamins and minerals in the blood compared to a non-liposomal MVM supplement. In a double-blind, randomized, and counterbalanced manner, 34 healthy men and women fasted for 12 h. Then, they ingested a non-liposomal (NL) or liposomal (L) MVM supplement and a standardized snack. Venous blood samples were obtained at 0, 2, 4, and 6 h after MVM ingestion and analyzed for a panel of vitamins and minerals. Plasma levels of vitamins and minerals and mean changes from baseline with 95% confidence intervals (CIs) were analyzed using general linear model statistics with repeated measures. The observed values were also entered into pharmacokinetic analysis software and analyzed through univariate analysis of variance with repeated measure contrasts. The results revealed an overall treatment x time interaction effect among the vitamins and minerals evaluated ( = 0.051, ηp2 = 0.054, moderate effect). Differences between treatments were also observed in volume distribution area (vitamin E, iron), median residence time (vitamin E, iron), volume distribution area (iron), volume of distribution steady state (vitamin A, E, iron), clearance rates (vitamin A, E), elimination phase half-life (vitamin E, iron), distribution/absorption phase intercept (vitamin A), and distribution/absorption phase slope and rate (vitamin C, calcium). Vitamin volume distribution was lower with liposomal MVM ingestion than non-liposomal MVM sources, suggesting greater clearance and absorption since similar amounts of vitamins and minerals were ingested. These findings indicate that coating a MVM with liposomes affects individual nutrient pharmacokinetic profiles. Additional research should evaluate how long-term supplementation of liposomal MVM supplements may affect vitamin and mineral status, nutrient function, and/or health outcomes.
Topics: Female; Humans; Male; Dietary Supplements; Iron; Liposomes; Minerals; Vitamin A; Vitamin E; Vitamin K; Vitamins; Double-Blind Method
PubMed: 37447400
DOI: 10.3390/nu15133073 -
Nutrients Dec 2023The purpose of this study was to assess the effects of protein and carbohydrate supplementation, with and without creatine, on occupational performance in firefighters. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The purpose of this study was to assess the effects of protein and carbohydrate supplementation, with and without creatine, on occupational performance in firefighters.
METHODS
Using a randomized, double-blind approach, thirty male firefighters (age: 34.4 ± 8.4 yrs., height: 1.82 ± 0.07 m; weight: 88.6 ± 12.5 kg; BF%: 17.2 ± 5.8%) were randomized to receive either (A.) 25 g of whey protein isolate + 25 g of carbohydrate powder (ProCarb group); or (B.) ProCarb + 5 g of creatine (Creatine group) in a double-blind fashion over a period of 21-26 days (depending on shift rotations) to evaluate the impact of supplementation on occupation-specific performance. At baseline and following supplementation, firefighters completed a battery of tests. These tests included an aerobic speed test on an air-braked cycle ergometer followed by the hose carry, body drag, stair climb, and Keiser sled hammer for time.
RESULTS
No significant differences in measures of performance were observed at baseline ( > 0.05). There was a significant main effect for time observed for rescue, stair climb, total time to completion, and time trial performance ( < 0.05). There was a significant group × time ( < 0.05) interaction for rescue and forcible entry. Independent sample -tests indicated that the Creatine group experienced a greater reduction (from baseline) in completion time for the rescue (1.78 ± 0.57 s, 95% CI: 0.61, 2.95 s, = 0.004) and forcible entry (2.66 ± 0.97 s, 95% CI: 0.68, 4.65 s, = 0.01) tests compared to the ProCarb group. No significant group × time interactions were observed for the hose line advance, stair climb, total time to completion, and time trial performance ( > 0.05).
CONCLUSIONS
The addition of supplemental creatine to a protein and carbohydrate supplement to the diet of career firefighters throughout a three week period improves occupational performance in firefighters in specific areas of high-intensity, repetitive actions.
Topics: Male; Humans; Adult; Creatine; Firefighters; Dietary Supplements; Carbohydrates; Double-Blind Method
PubMed: 38140393
DOI: 10.3390/nu15245134