scholarly journals CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e021000 ◽  
Author(s):  
Dan Siskind ◽  
Nadia Friend ◽  
Anthony Russell ◽  
John J McGrath ◽  
Carmen Lim ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Weight Gain ◽  
Controlled Trial ◽  
Adjunctive Treatment ◽  
Double Blind ◽  
Human Research Ethics ◽  
Increased Risk ◽  
Point Body ◽  
Randomised Controlled

IntroductionClozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation.Methods and analysisA 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants.Ethics and disseminationEthics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds.Trial registration numberACTRN12617001547336; Pre-results.

scholarly journals CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine

2021 ◽  
Vol 11 ◽  
pp. 204512532110452
Author(s):  
Dan Siskind ◽  
Anthony W. Russell ◽  
Shuichi Suetani ◽  
Dylan Flaws ◽  
Steve Kisely ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Adjunctive Treatment ◽  
Metformin Group ◽  
Secondary Outcomes ◽  
Gain Loss ◽  
Randomised Controlled

Background: There is limited evidence on interventions to minimise weight gain at clozapine commencement. We compared the effect of adjunctive metformin versus placebo at clozapine initiation. Methods: People with schizophrenia commencing on clozapine were randomised to either metformin or placebo for 24 weeks. The primary outcome was difference in the change of body weight. Secondary outcomes included comparative rates of weight gain of more than 5%, overall weight gain/loss, and differences in metabolic and psychosis outcomes. Results: The study was closed prematurely in March 2020 due to COVID-19 restrictions. Ten participants were randomised to each of the metformin and placebo groups. Eight metformin group and five placebo group participants completed the trial and were included in the analysis. The study was insufficiently powered to detect difference between the metformin and placebo groups for the primary outcome of change in weight (0.09 kg vs 2.88 kg, p = 0.231). In terms of secondary outcomes, people in the metformin group were significantly less likely to gain >5% of their body weight (12.5% vs 80%, p = 0.015) and were more likely to lose weight (37.5% vs 0% p = 0.024) compared to placebo. There was no difference between the groups in terms of adverse drug reactions (ADRs). Conclusion: While limited by the forced premature closure of the trial due to COVID19, the findings from this randomised controlled trial are promising. Clozapine and metformin co-commencement may be a promising treatment to prevent clozapine-associated weight gain, especially given the low rates of ADRs associated with metformin. This supports the consideration of use of metformin to prevent weight gain in people initiated on clozapine; however, further studies are needed to confirm this finding. Trial registration: ACTRN12617001547336

scholarly journals Relations of body weight status in early adulthood and weight changes until middle age with metabolic syndrome in the Chinese population

2017 ◽  
Vol 4 (11) ◽  
pp. 4011
Author(s):  
Liancheng Zhao ◽  
Huanhuan Liu ◽  
Long Zhou ◽  
Ying Li ◽  
Min Guo ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Weight Gain ◽  
Weight Change ◽  
Chinese Population ◽  
Weight Status ◽  
Early Adulthood ◽  
Weight Changes ◽  
Body Weight Status ◽  
Increased Risk

Background: The evidences for the relationship between long-term weight gain and metabolic syndrome (MetS) in Chinese population were limited. Therefore, this study aims to explore the association of body weight status in early adulthood and weight changes with MetS.Methods: Data from China Multicenter Collaborative Study of Cardiovascular Epidemiology including 12808 participants aged 35–59 were used. Participants were surveyed for cardiovascular risk factors and a self-reported weight at age 25, which was defined as early adulthood. Weight change was calculated as the difference between baseline weight and early adulthood weight. MetS was defined according to AHA/NHLBI definition in 2009. Multivariate logistic regression model was used to examine the association between early adulthood weight status, weight change and MetS.Results: Mean age of participants was 46.7 years, including 6134 men and 6674 women. The overall prevalence of MetS was 21.8%. After adjusted for age, sex and other confounding factors, both BMI at 25 age and weight gain were positively associated with the risk of MetS. Being overweight (BMI, 24–27.9 kg m-2) or obese (BMI ≥28 kg m-2) at early adulthood was related to an increased risk of MetS, the odds ratio (OR) and 95%confidence interval (CI) was 3.24 (2.82–3.72) and 13.31 (8.72–20.31). In addition, weight gain was also associated with higher risk of MetS (P for trend<0.01).Conclusions: Overweight and obesity in early adulthood and weight gain were both independently related to an increased risk of MetS in the middle-aged Chinese men and women. 

scholarly journals Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoying Tian ◽  
Giorgia Cioccoloni ◽  
Joanna H. Sier ◽  
Khalid M. Naseem ◽  
James L. Thorne ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Health Benefits ◽  
Blood Platelet ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Study Results ◽  
Randomised Controlled

Abstract Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 2021

scholarly journals Delayed postprandial TAG peak after intake of SFA compared with PUFA in subjects with and without familial hypercholesterolaemia: a randomised controlled trial

2018 ◽  
Vol 119 (10) ◽  
pp. 1142-1150 ◽  
Author(s):  
Linn K. L. Øyri ◽  
Patrik Hansson ◽  
Martin P. Bogsrud ◽  
Ingunn Narverud ◽  
Geir Florholmen ◽  
...  
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Controlled Trial ◽  
Lipid Lowering ◽  
Double Blind ◽  
Fat Quality ◽  
Postprandial Lipid Metabolism ◽  
Increased Risk ◽  
Lipid Response ◽  
Postprandial Lipid ◽  
Randomised Controlled

AbstractPostprandial hypertriacylglycerolaemia is associated with an increased risk of developing CVD. How fat quality influences postprandial lipid response is scarcely explored in subjects with familial hypercholesterolaemia (FH). The aim of this study was to investigate the postprandial response of TAG and lipid sub-classes after consumption of high-fat meals with different fat quality in subjects with FH compared with normolipidaemic controls. A randomised controlled double-blind cross-over study with two meals and two groups was performed. A total of thirteen hypercholesterolaemic subjects with FH who discontinued lipid-lowering treatment 4 weeks before and during the study, and fourteen normolipidaemic controls, were included. Subjects were aged 18–30 years and had a BMI of 18·5–30·0 kg/m2. Each meal consisted of a muffin containing 60 g (70 E%) of fat, either mainly SFA (40 E%) or PUFA (40 E%), eaten in a random order with a wash-out period of 3–5 weeks between the meals. Blood samples were collected at baseline (fasting) and 2, 4 and 6 h after intake of the meals. In both FH and control subjects, the level of TAG and the largest VLDL sub-classes peaked at 2 h after intake of PUFA and at 4 h after intake of SFA. No significant differences were found in TAG levels between meals or between groups (0·25≤P≤0·72). The distinct TAG peaks may reflect differences in the postprandial lipid metabolism after intake of fatty acids with different chain lengths and degrees of saturation. The clinical impact of these findings remains to be determined.

Sign in / Sign up

Export Citation Format

Share Document