Skip to main content
OpenTrials
Completed

NCT Number: NCT03770325

A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Cardiovascular Risk Factor

Age range

20 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Li Ka Shing Faculty of Medicine

Hong Kong

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

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

Treatment and study plan

Berberine

Drug

Purified berberine (500 mg orally twice a day) in tablets for 12 weeks

Placebo

Drug

Placebo tablets, prepared with the same appearance, for 12 weeks

Primary outcomes

  1. lipid profile

    Time frame: change from baseline lipid profile at 8 weeks

    LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L

  2. lipid profile

    Time frame: change from baseline lipid profile at 12 weeks

    LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L

  3. blood pressure

    Time frame: change from baseline blood pressure at 8 weeks

    systolic blood pressure and diastolic blood pressure in mmHg

  4. blood pressure

    Time frame: change from baseline blood pressure at 12 weeks

    systolic blood pressure and diastolic blood pressure in mmHg

  5. thromboxane A2

    Time frame: change from baseline thromboxane A2 at 8 weeks

    thromboxane A2 in mmol/L

  6. thromboxane A2

    Time frame: change from baseline thromboxane A2 at 12 weeks

    thromboxane A2 in mmol/L

  7. testosterone

    Time frame: change from baseline testosterone at 8 weeks

    testosterone in mmol/L

  8. testosterone

    Time frame: change from baseline testosterone at 12 weeks

    testosterone in mmol/L

  9. body mass index (BMI)

    Time frame: change from baseline body mass index at 8 weeks

    weight and height will be combined to report BMI in kg/m^2

  10. body mass index (BMI)

    Time frame: change from baseline body mass index at 12 weeks

    weight and height will be combined to report BMI in kg/m^2

  11. waist hip ratio

    Time frame: change from baseline waist hip ratio at 8 weeks

    waist circumstance and hip circumstance will be combined to report waist hip ratio

  12. waist hip ratio

    Time frame: change from baseline waist hip ratio at 12 weeks

    waist circumstance and hip circumstance will be combined to report waist hip ratio

  13. fasting glucose

    Time frame: change from baseline fasting glucose at 8 weeks

    fasting glucose in mmol/L

  14. fasting glucose

    Time frame: change from baseline fasting glucose at 12 weeks

    fasting glucose in mmol/L

  15. fasting insulin

    Time frame: change from baseline fasting insulin at 8 weeks

    fasting insulin in mmol/L

  16. fasting insulin

    Time frame: change from baseline fasting insulin at 12 weeks

    fasting insulin in mmol/L

  17. liver function

    Time frame: change from baseline fasting insulin at 8 weeks

    Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L

  18. liver function

    Time frame: 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

  19. sex hormone binding globulin (SHBG)

    Time frame: change from baseline SHBG at 8 weeks

    SHBG in nmol/L

  20. sex hormone binding globulin (SHBG)

    Time frame: change from baseline SHBG at 12 weeks

    SHBG in nmol/L

  21. thrombin time

    Time frame: change from baseline thrombin time at 8 weeks

    thrombin time in sec

  22. thrombin time

    Time frame: change from baseline thrombin time at 12 weeks

    thrombin time in sec

Sponsors and collaborators

Lead sponsor

The University of Hong Kong

Other

Collaborators

  • Food and Health Bureau, Hong Kong

Registry information

Official study title

Effect of Berberine on Cardiovascular Disease Risk Factors: a Mechanistic Randomized Controlled Trial

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Dec 10, 2018
Registry last updated
Nov 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.