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Frontiers in Pharmacology 2024Mefunidone is a novel synthetic compound and is better when compared to pirfenidone for the anti-fibrotic treatment of renal fibrosis in end-stage renal disease. We...
BACKGROUND
Mefunidone is a novel synthetic compound and is better when compared to pirfenidone for the anti-fibrotic treatment of renal fibrosis in end-stage renal disease. We conducted this first-in-human, phase I clinical trial to determine the safety, tolerability, and pharmacokinetic (PK) (including food effect) profiles of mefunidone administered orally as single and multiple ascending doses in healthy subjects.
METHODS
Part A assessed single ascending doses of mefunidone from 25 mg to 800 mg or placebo once daily in the fasting state. Part A also assessed the effect of food on tolerability and PK in the 100 mg cohort. Part B consisted of three treatment groups who received 100 mg, 200 mg, or 400 mg of mefunidone or placebo twice daily (BID, ) on days 1-6 and once in the morning on day 7.
RESULTS
Single oral doses of mefunidone up to 800 mg and multiple doses of mefunidone up to 400 mg BID were all well-tolerated. Mefunidone behaved with ideal dose proportionality within the single-dose range of 50 mg-600 mg and the multiple-dose range of 100 mg BID to 400 mg BID by day 7. High-fat fed conditions led to a delay in T by approximately 1 h and a slight reduction of approximately 20% in C compared to that in fasting conditions, but it did not significantly affect systemic exposure.
CONCLUSION
Mefunidone exhibited favorable pharmacokinetics and safety profiles. The present study informed and supported further developmental clinical studies of mefunidone.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov, identifier CXHL1900206.
PubMed: 38933669
DOI: 10.3389/fphar.2024.1414066 -
BMJ Open Sport & Exercise Medicine 2024No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity...
No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor performance, as well as the range of motion of Paralympic athletes. The study will be a triple-blinded, randomised controlled trial. Twenty-four athletes aged 18-45 in T35-T38 groups of the International Paralympic Committee classification will be included in the study. Twelve participants will receive dry needling of the quadriceps and gastrocnemius muscles, and 12 will receive placebo treatment with sham needles at similar points. We will assess the spasticity of the quadriceps and gastrocnemius muscles using the Modified Ashworth Scale, evaluate motor function using the Selective Control Assessment of the Lower Extremity Scale and measure ankle range of motion (ROM) with a goniometer. Considering our hypothesis, the athletes who will undergo the dry needling are supposed to achieve better improvements in spasticity, ROM and motor performance. This study can provide useful information to help better decide on managing complications in Paralympics and its long-term outcomes, to cover the current lack in the literature.
PubMed: 38933371
DOI: 10.1136/bmjsem-2024-002096 -
Journal of Diabetes and Metabolic... Jun 2024This study was carried out to evaluate the effects of probiotics administration on clinical status and metabolic profiles in diabetic retinopathy (DR) patients.
PURPOSE
This study was carried out to evaluate the effects of probiotics administration on clinical status and metabolic profiles in diabetic retinopathy (DR) patients.
METHODS
This randomized, double-blind, placebo-controlled trial was conducted among 72 DR patients. Subjects received probiotics including , , , daily (2 × 10 CFU/each strain) ( = 36) or placebo (starch) ( = 36) and were instructed to take one capsule daily for 12 weeks. Finally, 55 participants [probiotic group ( = 30) and placebo group ( = 25)] completed the study. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles. To determine the effects of probiotic supplementation on clinical symptoms and biochemical variables, we used one-way repeated measures analysis of variance.
RESULTS
After the 12-week intervention, compared with the placebo, probiotic supplementation significantly decreased means serum insulin concentrations (Probiotic group: -4.9 ± 6.5vs. Placebo group: 3.0 ± 7.7 µIU/mL, P<0.001), homeostatic model assessment for insulin resistance (Probiotic group: -2.5 ± 3.8 vs. Placebo group: 1.1 ± 2.7, P<0.001) and hemoglobin A1c (HbA1C) (Probiotic group: -0.4 ± 0.7 vs. Placebo group: -0.02 ± 0.2%, P=0.01), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (Probiotic group: 0.02 ± 0.03 vs. Placebo group: -0.03 ± 0.04, P<0.001). There was no significant effect of probiotic administration on other metabolic profiles and clinical symptoms.
CONCLUSIONS
Overall, probiotic supplementation after 12 weeks in DR patients had beneficial effects on few metabolic profiles. This study was registered under the Iranian website for clinical trials as http://www.irct.ir: IRCT20130211012438N29.
PubMed: 38932908
DOI: 10.1007/s40200-024-01399-2 -
Journal of Diabetes and Metabolic... Jun 2024Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed...
The dietary supplements effect on metabolic markers in non-pharmacologically managed gestational diabetes mellitus patients: a systematic review and meta-analysis and meta-regression of randomized controlled trials.
BACKGROUND
Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed gestational diabetes mellitus patients (GDM), a rigorous meta-analytic compendium lacks in the context. Therefore, this study aims to address this evidence gap.
METHOD
Eligible trials retrieved from searches in the PubMed, Embase, and Scopus databases were appraised using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The weighted mean differences (WMD) between dietary supplements and placebo were estimated using random-effect meta-analysis models for plasma glycemic and lipid markers. Meta-regression analysis ensued for effect modifier identification. The statistical significance estimation happened at < 0.05 (95% confidence interval).
RESULTS
This review included 19 trials (mostly Iranian and of low risk of bias primarily) of > 8000 GDM patients. Meta-analysis showed favorable effects of dietary supplementation on fasting plasma glucose (WMD: -5.42 mg/dL, p < 0.001), homeostasis model assessment indexes- insulin resistance (HOMA-IR; WMD: -1.02, p < 0.001), quantitative insulin sensitivity check index (WMD: 0.01, p < 0.001), total cholesterol (TC; WMD: -7.70 mg/dL, = 0.006), triglycerides (WMD: -10.23 mg/dL, = 0.0083), TC/high-density lipoprotein (WMD: -0.31 mg/dL, < 0.001), low-density lipoprotein (WMD: -5.79 mg/dL; < 0.001) and very-low-density lipoprotein (WMD: -5.67 mg/dL, < 0.001) levels. However, the HOMA- ß-cell function didn't increase (WMD: -17.91, < 0.001). Baseline maternal age ( = 0.28, = 0.014) and GDM diagnostic criteria ( = 0.90, = 0.012) were effect moderators of HOMA-IR and body mass index (BMI) ( = 6.07, = 0.022) and supplement type (solo versus combined) ( = 14.99, = 0.006) were effect moderators of triglyceride levels.
CONCLUSION
Altogether, antenatal dietary supplements achieved control over plasma glycemic and lipid profiles in non-pharmacologically treated GDM patients. Maternal age and GDM diagnostic criteria moderated HOMA-IR levels. BMI and supplement-type moderated triglyceride levels.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01369-0.
PubMed: 38932907
DOI: 10.1007/s40200-023-01369-0 -
Journal of Diabetes and Metabolic... Jun 2024Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this...
PURPOSE
Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this double-blind randomized clinical trial study investigated the impact of probiotics supplementation on anthropometric and biochemical parameters in obese adults.
METHODS
In this study, 66 obese patients with BMI in the range of 30-40 kg/m2, were enrolled and randomly assigned to either the probiotic or placebo group. They all received advice to maintain a reduction in daily caloric intake and for 3 months received two unlabeled placebo or probiotic (, , ) capsules per day. For each participant demographic and medical history questionnaire, semi-quantitative food frequency questionnaire (FFQ), and modifiable activity questionnaire (MAQ) were completed at the beginning of the study and anthropometric and biochemical measurements were done before and after intervention.
RESULTS
At the end of the trial 25 subjects in the probiotic group and 26 subjects in the placebo group were analyzed. After the intervention, in the probiotic group, the level of fasting insulin was reduced significantly ( < 0.05). Weight, body mass index, waist circumference, and hip circumference decreased within both groups. This reduction amount's mean was higher in the probiotic group. Also, total cholesterol, triglycerides, and LDL levels were decreased, but not statistically significant.
CONCLUSION
This study may suggest the potential of this combined probiotic supplement for treating obesity and related metabolic disorders. However, further researches are warranted for a definitive determination of its properties.
PubMed: 38932862
DOI: 10.1007/s40200-024-01400-y -
Journal of Diabetes and Metabolic... Jun 2024The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence... (Review)
Review
Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis.
PURPOSE
The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients.
METHODS
PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785).
SUMMARY
This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01309-y.
PubMed: 38932855
DOI: 10.1007/s40200-023-01309-y -
Journal of Diabetes and Metabolic... Jun 2024Sodium glucose co-transporter2 (SGLT2) inhibitors have exhibited cardioprotective properties in diabetes patients. The aim of this study was to investigate the effect of...
Empagliflozin improves left ventricular ejection fraction and end systolic volume in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD trial.
BACKGROUND
Sodium glucose co-transporter2 (SGLT2) inhibitors have exhibited cardioprotective properties in diabetes patients. The aim of this study was to investigate the effect of Empagliflozin on changes in echocardiographic parameters.
METHODS
This was a post hoc analysis of the EMPA-CARD trial which was a multicenter, triple-blind randomized controlled trial. Type 2 diabetes mellitus patients with concomitant history of coronary artery disease were randomized on a 1:1 ratio into two groups receiving either 10 mg/day Empagliflozin or placebo. Patients with a history of heart failure (NYHA class 3-4) and ejection fraction (EF) < 40% were excluded. Trans-thoracic echocardiography was performed at baseline and at 26 weeks of intervention.
RESULTS
A total of 69 (Empagliflozin = 39 and placebo = 30) patients underwent echocardiography. Significant changes were observed for left ventricular ejection fraction [standard error (SE) = 0.76; beta (95% correlation interval (CrI)] = -5.558 (-7.25; -4.18) and left ventricular end-systolic volume (SE = 1.38; beta (95% CrI) = 3.915 (1.2; 0.66). Other echocardiographic parameters relating to right ventricular or atrial function did not change significantly.
CONCLUSION
Empagliflozin can have cardioprotective benefits in subjects without HF. Further studies are required to determine the effect of Empagliflozin in non-HF patients.
TRIAL REGISTRATION
The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.
PubMed: 38932825
DOI: 10.1007/s40200-024-01393-8 -
Obesity (Silver Spring, Md.) Jul 2024The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials.
METHODS
The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo.
RESULTS
Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups.
CONCLUSIONS
The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability.
Topics: Humans; Glucagon-Like Peptides; Male; Female; Adult; Middle Aged; Obesity; Treatment Outcome; Weight Loss; Injections, Subcutaneous; Double-Blind Method; Glucagon-Like Peptide-1 Receptor; White People; Hispanic or Latino; Anti-Obesity Agents; Ethnicity; Hypoglycemic Agents
PubMed: 38932728
DOI: 10.1002/oby.24042 -
Vaccines Jun 2024Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically...
Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut , as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.
PubMed: 38932337
DOI: 10.3390/vaccines12060608 -
Pharmaceuticals (Basel, Switzerland) May 2024Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly... (Review)
Review
Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
PubMed: 38931356
DOI: 10.3390/ph17060689