A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine
- Registration Number
- NCT03770325
- Lead Sponsor
- The University of Hong Kong
- Brief Summary
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a comprehensive systematic review and meta-analysis of 27 randomized controlled trials (RCTs), berberine effectively reduced low density lipoprotein cholesterol (LDL-c) (-0.65 mmol/L, 95% confidence interval (CI) -0.75 to -0.56), triglycerides (TG) (-0.39 mmol/L, 95% CI -0.59 to -0.19), total cholesterol (TC) (-0.66 mmol/L, 95% CI -1.02 to -0.31) and increased high density lipoprotein cholesterol (HDL-c) (0.07mmol/L, 95% CI 0.04 to 0.1).1 Notably, no serious adverse event has been reported in these trials,1 suggesting a good tolerability of berberine. The mechanism by which berberine exerts a protective role in atherosclerosis is unclear. Protoberberines have been identified as a new inhibitor of AKR1C3, an enzyme responsible for the regulation of steroid hormone action.3 The investigators propose to examine the effects of berberine on a set of well-established CVD risk factors including lipids, systolic and diastolic blood pressure, coagulation factors, adiposity, fasting glucose, insulin, and liver function, as well as to examine potential mediation via testosterone and/or sex hormone binding globulin using a mechanistic, randomized, double-blind, placebo-controlled trial in Chinese men with hyperlipidemia.
- Detailed Description
Objectives: to assess the effect of berberine on a set of well-established CVD risk factors, including lipids, systolic and diastolic blood pressure, coagulation factors, fasting glucose, insulin, adiposity (body mass index (BMI) and waist-hip ratio (WHR)) and the mediation via testosterone and/or sex hormone binding globulin using a mechanistic, parallel RCT.
Study design: a mechanistic, randomized, double-blind, placebo-controlled, parallel trial in 84 Chinese men in Hong Kong.
Interventions: the eligible participants will be randomized to take berberine (500 mg orally twice a day) or placebo for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention.
Data analysis and expected results: the investigators will use an intention to treat analysis, with multiple imputation for missing data. The investigators will compare the baseline characteristics of participants in the two arms using analysis of variance. The investigators will assess the effects of berberine on changes in CVD risk factors using analysis of variance, and the mediation using causal mediation analysis. Compared to the placebo group, the participants receiving berberine are expected to have lower burden of cardiovascular disease risk factors at the end of the intervention. These effects may be mediated or partly mediated by lowering testosterone.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 84
-
Men, who are
- aged 20 to 65 years
- of Chinese ethnicity
- with hyperlipidemia, defined as TG greater than 150 mg/dl (1.70 mmol/L), TC greater than 200 mg/dl (5.16 mmol/L), and/or LDL-c greater than 100 mg/dl (2.58 mmol/L)
- willing to make return visits
- not currently receiving hormone replacement therapy, such as testosterone replacement therapy, in the past 12 months
- not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month
- free of any congenital diseases, including familial hypercholesterolemia
- free of any infectious diseases, e.g. seasonal influenza
- free of anemia and glucose-6-phosphate dehydrogenase deficiency
- with no history of any chronic diseases including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders.
- All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo placebo (500 mg orally twice a day) Berberine Berberine berberine (500 mg orally twice a day)
- Primary Outcome Measures
Name Time Method waist hip ratio change from baseline waist hip ratio at 12 weeks waist circumstance and hip circumstance will be combined to report waist hip ratio
fasting glucose change from baseline fasting glucose at 12 weeks fasting glucose in mmol/L
fasting insulin change from baseline fasting insulin at 12 weeks fasting insulin in mmol/L
liver function change from baseline fasting insulin at 12 weeks Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
sex hormone binding globulin (SHBG) change from baseline SHBG at 12 weeks SHBG in nmol/L
thrombin time change from baseline thrombin time at 12 weeks thrombin time in sec
lipid profile change from baseline lipid profile at 12 weeks LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
blood pressure change from baseline blood pressure at 12 weeks systolic blood pressure and diastolic blood pressure in mmHg
thromboxane A2 change from baseline thromboxane A2 at 12 weeks thromboxane A2 in mmol/L
testosterone change from baseline testosterone at 12 weeks testosterone in mmol/L
body mass index (BMI) change from baseline body mass index at 12 weeks weight and height will be combined to report BMI in kg/m\^2
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Li Ka Shing Faculty of Medicine
ðŸ‡ðŸ‡°Hong Kong, Hong Kong