scholarly journals Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4481
Author(s):  
Catherine McFarlane ◽  
Rathika Krishnasamy ◽  
Tony Stanton ◽  
Emma Savill ◽  
Matthew Snelson ◽  
...  
Keyword(s):  
Kidney Function ◽  
Controlled Trial ◽  
Retention Rates ◽  
Double Blind ◽  
Creatinine Concentration ◽  
Adult Participants ◽  
Synbiotic Supplementation ◽  
And Function ◽  
Stool Microbiota

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

scholarly journals Impacts of treatments on recurrence and 28-year survival of ischemic stroke patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Ann Wang ◽  
Tzy-Haw Wu ◽  
Shin-Liang Pan ◽  
Hsiu-Hsi Chen ◽  
Sherry Yueh-Hsia Chiu
Keyword(s):  
Ischemic Stroke ◽  
Cerebrovascular Disease ◽  
Cox Regression ◽  
Controlled Trial ◽  
Stroke Recurrence ◽  
Long Term Effects ◽  
Stroke Patients ◽  
Double Blind ◽  
Term Survival

AbstractAspirin and nicametate are well-established therapies for preventing recurrence and mortality from stroke in patients diagnosed as ischemic stroke. However, their respective effects on the recurrence, making allowance for the duration of recurrence and death without the occurrence of recurrence, and long-term survival have not been well elucidated. We aimed to evaluate long-term effect of two kinds of treatment on cerebrovascular death among ischemic stroke patients with or without the recurrence of stroke. Data used in this study were derived from the cohort based on a multicenter randomized double-blind controlled trial during 1992 to 1995 with the enrollment of a total of 466 patients with first-time non-cardioembolic ischemic stroke who were randomly allocated to receive aspirin (n = 222) or nicametate (n = 244). The trial cohort was followed up over time to ascertain the date of recurrence within trial period and death until Sep of 2019. The time-dependent Cox regression model was used to estimate the long-term effects of two treatments on death from cerebrovascular disease with and without recurrence. A total of 49 patients experienced stroke recurrence and 89 cerebrovascular deaths was confirmed. Patients treated with nicametate were more likely, but non statistically significantly, to have recurrence (aHR: 1.73, 95% CI 0.96–3.13) as compared with those treated by aspirin. Nicametate reduced the risk of cerebrovascular death about 37% (aHR: 0.63, 95% CI 0.41–0.97) compared with aspirin. The aspirin group had a lower recurrence rate than the nicametate group even with recurrence after 1–2 years of follow-up of first stroke but the latter had significantly reduced death from cerebrovascular disease for nicametate group, which requires more research to verify.

scholarly journals Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial

2021 ◽  
Author(s):  
Michael Berk ◽  
Bruno Agustini ◽  
Robyn L. Woods ◽  
Mark R. Nelson ◽  
Raj C. Shah ◽  
...  
Keyword(s):  
Older People ◽  
Controlled Trial ◽  
Double Blind ◽  
Term Management

scholarly journals Baseline Characteristics of Participants in a Randomized Controlled Trial of Metformin for Frailty Prevention

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 130-131
Author(s):  
Tiffany Cortes ◽  
Nicolas Musi ◽  
Chen-pin Wang ◽  
Joel Michalek ◽  
Sara Espinoza
Keyword(s):  
Randomized Controlled Trial ◽  
Glucose Tolerance ◽  
Physical Performance ◽  
Controlled Trial ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Randomized Controlled ◽  
Insulin Clamp ◽  
And Function

Abstract We are conducting a double-blind, randomized controlled trial of metformin for frailty prevention. Participants are adults aged 65+ years with pre-diabetes assessed by 2-hour oral glucose tolerance test (OGTT). Those who are frail (Fried criteria) are excluded. Participants are randomized to metformin (maximum dose of 2,000 mg/day) vs. placebo and followed for 2 years. The primary outcome is frailty (category and score); secondary outcomes are physical performance and function (short physical performance battery, 6-minute walk, lower extremity strength), systemic and skeletal muscle tissue inflammation, muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (OGTT), and body composition (dual-energy x-ray absorptiometry). Safety assessments occur every 3 months; frailty, systemic inflammation, and OGTT are assessed at baseline and every 6 months, and insulin clamp with muscle biopsies are assessed at baseline and every 12 months. To date, 85 subjects have been randomized; 120 completers are planned. Mean age is 72.8 ± 5.7 years, 55.3% are male, and 43.5% were Hispanic. Mean BMI is 30.2±5.8 kg/m2, waist circumference is 104.4 ±15.5 cm, fasting glucose is 102.3 ± 10.0 mg/dL, Hemoglobin A1c is 5.8 ±0.3, and glucose at 2 hours during OGTT is 167.3 ± 17.8 mg/dL. Metformin is being examined in this study as a potential therapeutic agent to prevent frailty in older adults with pre-diabetes. Findings from this trial may have future implications for the screening and potential treatment of pre-diabetes in older patients with metformin for the prevention of frailty.

scholarly journals The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo-controlled trial

2016 ◽  
Vol 116 (8) ◽  
pp. 1394-1401 ◽  
Author(s):  
Shahnaz Ahmadi ◽  
Mehri Jamilian ◽  
Maryam Tajabadi-Ebrahimi ◽  
Parvaneh Jafari ◽  
Zatollah Asemi
Keyword(s):  
Gestational Diabetes ◽  
Controlled Trial ◽  
Lipid Profiles ◽  
Model Assessment ◽  
Double Blind ◽  
Insulin Metabolism ◽  
Double Blind Placebo ◽  
Vldl Cholesterol ◽  
Freeze Dried ◽  
Synbiotic Supplementation

AbstractTo the best of our knowledge, data on the effects of synbiotic supplementation on markers of insulin metabolism and lipid concentrations in patients with gestational diabetes mellitus (GDM) are scarce. The aim of the current study was to determine the effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in GDM patients. In total, seventy patients with GDM aged 18–40 years were assigned to two groups – the synbiotic group (n 35) and the placebo group (n 35) – in this randomised, double-blind, placebo-controlled trial. Patients in the synbiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2×109 colony-forming units/g each) plus 800 mg inulin for 6 weeks. Fasting blood samples were collected at the beginning and week 6 to quantify related markers. After 6 weeks of intervention, compared with the placebo, synbiotic supplementation led to a significant decrease in serum insulin levels (−1·5 (sd 5·9) v. +4·8 (sd 11·5) µIU/ml, P=0·005), homoeostatic model assessment for insulin resistance (−0·4 (sd 1·3) v. +1·1 (sd 2·7), P=0·003) and homoeostatic model assessment for β cell function (−5·1 (sd 24·2) v. +18·9 (sd 45·6), P=0·008) and a significant increase in quantitative insulin sensitivity check index (+0·01 (sd 0·01) v. −0·007 (sd 0·02), P=0·02). In addition, synbiotic intake significantly decreased serum TAG (−14·8 (sd 56·5) v. +30·4 (sd 37·8) mg/dl, P<0·001) and VLDL-cholesterol concentrations (−3·0 (sd 11·3) v. +6·1 (sd 7·6) mg/dl, P<0·001) compared with the placebo. Overall, the results of this study demonstrate that taking synbiotic supplements for 6 weeks among patients with GDM had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations.

Colchicine in Behçet Syndrome: A Longterm Survey of Patients in a Controlled Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 735-738 ◽  
Author(s):  
Vedat Hamuryudan ◽  
Gulen Hatemi ◽  
Koray Tascilar ◽  
Sebahattin Yurdakul ◽  
Cem Mat ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Disease Stage ◽  
Early Disease ◽  
Double Blind ◽  
Behçet Syndrome ◽  
Behcet Syndrome ◽  
Cumulative Duration ◽  
Continuous Use ◽  
Early Disease Stage

Objective.To test the hypothesis that colchicine use during early disease decreases immunosuppressive use in Behçet syndrome (BS) in the long term.Methods.Patients with BS who participated in a double-blind, placebo-controlled trial of colchicine 16.6 ± 1.1 years ago were evaluated for immunosuppressive use during the posttrial period.Results.We could contact 90/116 patients; 28 (31%) received immunosuppressives during the posttrial period, 14 being from the colchicine arm. Posttrial colchicine use and cumulative duration were similar between patients who received immunosuppressives and those who did not.Conclusion.Continuous use of colchicine, even when initiated at an early disease stage, does not seem to decrease the use of immunosuppressives in the long term.

scholarly journals Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017121 ◽  
Author(s):  
Gowrie Balasubramaniam ◽  
Trisha Parker ◽  
David Turner ◽  
Mike Parker ◽  
Jonathan Scales ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Interleukin 1 ◽  
Scale Up ◽  
General Information ◽  
Primary Objective ◽  
Retention Rates ◽  
Acute Gout ◽  
Double Blind

IntroductionAcute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD).Methods and analysisASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies.Ethics and disseminationThe London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberEudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No.NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614–34090.

scholarly journals Ropivacaine 75mg versus placebo in perineal infiltration for analgesic efficacy at mid- and long-term for episiotomy repair in postpartum women- The ROPISIO study: a two-center, randomized, double-blind, placebo-controlled trial.

2020 ◽  
Author(s):  
Claire CARDAILLAC ◽  
Stéphane Ploteau ◽  
Aurélie Le Thuaut ◽  
Vincent Dochez ◽  
Norbert Winer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Perineal Pain ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Mediolateral Episiotomy ◽  
The Impact

Abstract Background Perineal pain due to episiotomy is commonly reported and can be severe enough to disturb the mother-infant dyad during the postpartum period. Its incidence at day 7 postpartum varies from 63% to 74%. Recent studies have already investigated the analgesic efficacy of perineal infiltration of ropivacaine after episiotomy, but have only focused on the immediate postpartum period (at 24 and 48 hours after birth). Large, adequately powered, multicenter, randomized controlled trials are required to evaluate the impact of ropivacaine infiltration on perineal pain and mid- and long-term quality of life before the widespread use of ropivacaine to prevent perineal pain after episiotomy can be recommended. Methods The ROPISIO study is a two-center, randomized, double-blind, placebo-controlled trial in La Roche sur Yon and Nantes, France. It will involve 272 women with vaginal singleton delivery and mediolateral episiotomy at term (≥ 37 weeks). Perineal infiltration (ropivacaine 75mg or placebo) will be administrated just after vaginal birth and before episiotomy repair. The primary outcome will be the analgesic efficacy at day 7 postpartum (mid-term), defined by the numerical rating scale of pain (ENS NRS) strictly superior to 3/10 on the perineal repair area. Secondary outcomes will be the analgesic efficacy (ENS NRS), the impact of pain on daily behavior, on the quality of life (36-Item Short Form Health Survey), on the occurrence of symptoms of postpartum depression (Edinburgh Postnatal Depression Scale) and on sexuality (Female Sexual Function Index) at 3 and 6 months (long-term) using validated online questionnaires. This study will have 90% power to show approximately 30% relative risk reduction in the incidence of perineal pain at day 7, from 70.0% to 50.0%. Discussion Ropivacaine is a promising candidate drug, inexpensive, easy to administer, and would be suitable to include in the routine management of deliveries in labor ward. This study will investigate if perineal ropivacaine infiltration just after birth can reduce mid- and long-term postpartum pain and increase quality of life in women with mediolateral episiotomy.

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