A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine

The University of Hong Kong (HKU)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Cardiovascular Risk Factor

Treatments: Drug: Berberine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03770325

15162621

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 patients

Sex: Male

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men, who are

  1. aged 20 to 65 years
  2. of Chinese ethnicity
  3. 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)
  4. willing to make return visits
  5. not currently receiving hormone replacement therapy, such as testosterone replacement therapy, in the past 12 months
  6. not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month
  7. free of any congenital diseases, including familial hypercholesterolemia
  8. free of any infectious diseases, e.g. seasonal influenza
  9. free of anemia and glucose-6-phosphate dehydrogenase deficiency
  10. with no history of any chronic diseases including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders.

Exclusion criteria

• All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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84 participants in 2 patient groups, including a placebo group

Berberine

Experimental group

Description:

berberine (500 mg orally twice a day)

Treatment:

Drug: Berberine

Placebo

Placebo Comparator group

Description:

placebo (500 mg orally twice a day)

Treatment:

Drug: Placebo