Clinical Trials in Degenerative Diseases

Sacubitril/valsartan improves ejection fraction in heart failure with reduced ejection fraction: A retrospective study Walid Ibrahim, Ahmed S Yassin, Ahmed Subahi, Hassan Mohamed, Ayman Khaddam, Muhammad Bajwa, Ashraf Abugroun, Amir Kaki, Mahir Elder, Tamam Mohamad Clinical Trials in Degenerative Diseases 2018 3(4):119-122 Background and objectives: The discovery and introduction of Neprilysin inhibitor in treating chronic heart failure (New York Heart Association class II–IV) with reduced ejection fraction (HFrEF) is a remarkable landmark in therapy. The clinical outcome of reducing the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure was demonstrated at the large randomized, double blind, “Angiotensin-Neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF trial).” We studied a total of 228 patients with HFrEF who was recently started on sacubitril/valsartan (EntrestoTM; previously known as LCZ696) testing the hypothesis of improving ejection fraction with sacubitril/valsartan, defined as an increase of ejection fraction from the baseline before treatment by 10–15%. Methods: This is a single-center, retrospective, descriptive study. The data was collected from the charts of patients followed up for a mean of 4.7 weeks after initiation of treatment with sacubitril/valsartan. A total of 228 patients with heart failure were prescribed 200 mg of sacubitril/valsartan twice daily, an improvement in ejection fraction by 10–15% was considered a successful response. Results: Out of the 228 patients, 51.3% showed a successful response. Most of the patients 97.9% and 58.0% were taking beta-blockers and aspirin respectively. The absolute number of black patients who improved was higher than others ethnic groups. However, the higher percentage of ejection fraction improvement 71% was reported among other ethnicities (not blacks or Caucasians). Patients without episodes of hospitalization showed better improvement than those with one or more episodes. Conclusion: In a predominantly black population with HFrEF, sacubitril/valsartan has shown improvement in ejection fraction effect. This finding was independent of other risk factors and concomitant heart failure treatment; however, further studies are recommended to validate this result. Ethics: Ethical approval of this study was obtained from the Research Committee, DMC/Wayne State University (IRB# 015618MP4X) on February 14, 2018.

Efficacy and safety of Vidangadi Yoga (ayurvedic polyherbal medicine) in type 2 diabetes mellitus: A randomized controlled clinical study Shailesh Vinayak Deshpande, Krutika Subhash Jadhav Clinical Trials in Degenerative Diseases 2018 3(4):123-129 Background and objectives: Incidence of diabetes mellitus is increasing due to genetic predisposition, high body fat, and insulin resistance. Though multiple oral hypoglycaemic agents and insulin are available, these are associated with side effects, primary and secondary failure. Hence, evaluation of antidiabetic potential of medicines described in traditional health sciences such as Ayurveda (Indian system of medicine) is also important. This study aimed to assess the efficacy and safety of Vidangadi Yoga (ayurvedic polyherbal medicine) and metformin in the management of type 2 diabetes mellitus (T2DM) based on biochemical parameters and adverse events. Methods: In this prospective, randomized, open-label, active-controlled, two-arm study, 61 patients with T2DM were included and randomly divided two groups. Patients in the Vidangadi Yoga group received Vidangadi Yoga tablet 500 mg thrice daily before food with water, while patients in the metformin group received metformin 500 mg after food twice daily for 90 days. Subjects were asked to undergo follow-up at the interval of 15 days until the completion of 90 days. Assessment was done on changes observed in fasting and postprandial blood glucose, glycosylated haemoglobin, lipid profile, haemogram, hepatic, renal profile, and clinical symptoms. Results: After 90 days of medication, fasting and postprandial blood glucose levels in both groups were significantly decreased when compared with baseline (P < 0.001). There were no significant differences in fasting and postprandial blood glucose levels between both groups. After 90 days of medication, haemogram, and hepatic and renal profiles (safety parameters) in the two groups were not significantly different from baseline. No adverse events were related with the use of the studied medicine. Conclusion: Vidangadi Yoga exhibits equivalent efficacy to metformin and is safe in lowering fasting and postprandial blood glucose levels. Ethics and trial registration: This study was approved by the institutional ethics committee of PDEA’s College of Ayurved and Research Centre, Pune, Maharashtra, India (approval number 6833) on March 22, 2014 and was registered with Clinical Trials Registry- India (CTRI) (No. CTRI/2015/04/005719) on April 25, 2015.

Effects of a heel raise program on central hemodynamics and cognitive performance in chronic stroke: Study protocol for a randomized, controlled, crossover trial Andrew Mitchelmore, Danielle Lambrick, Simon Jobson, Lee Stoner, James Faulkner Clinical Trials in Degenerative Diseases 2018 3(4):130-134 Background and objectives: As survival rates after incident stroke increase, the burden caused by secondary stroke and pressure placed on rehabilitation centers also rises. Lifestyle interventions have the potential to drive secondary-prevention treatments. Low-intensity interventions, such as heel raises, may offer a simple method of improving cardiovascular health and cognitive ability in chronic stroke. Here we present a protocol which attempts to determine whether a heel raise training program can improve markers of vascular health and cognitive function. Design: A randomized, controlled, crossover trial. Methods: Fifteen participants (> 3 months post-stroke diagnosis) will be randomly assigned to an intervention-first group (n = 8) or a control-first group (n = 7). In the intervention period, participants will complete 170 heel raises per day for 10 weeks. Heel raises will be completed in sets of ten, within a period of 170 minutes, from a seated position. In the control period, participants will go about their normal lives for 10 weeks. On completion of each program, participants will have a 4-week washout before commencing the alterative arm. Outcome measures: The primary outcomes (pre- and post-measures of peripheral and central blood pressure and pulse wave velocity) will be recorded, as these variables are strongly linked to vascular health after stroke. Secondary outcomes (cognitive function and maximal voluntary contractions) will be assessed using the Stroop task and electromyography respectively. A mixed-model analysis of variance will identify whether a heel raise intervention has a significant effect on the proposed primary and secondary outcome variables. Discussion: The potential improvements in vascular health may demonstrate that lower-limb heel raise exercise is a beneficial exercise stimulus for this population group. Ethics and dissemination: The protocol received ethical approval from the University of Winchester Ethics Committee (approval No. BLS/17/11) on November 30, 2017 and will be conducted in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be obtained from all participants. Recruitment began in June 2018. Analysis of the primary and secondary outcome measures will be completed in January 2019, and the study will finish in February 2019. Trial registration: The study was registered with ClinicalTrials.gov (NCT03423433) on February 6, 2018.