A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine
Condition: Cardiovascular Risk Factor
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Berberine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Purified berberine (500 mg orally twice a day) in tablets for 12 weeks; Placebo tablets, prepared with the same appearance, for 12 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention