A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine

NCT ID: NCT03770325

Last Updated: 2020-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2020-11-01

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.

Conditions

Cardiovascular Risk Factor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Berberine

berberine (500 mg orally twice a day)

Group Type: EXPERIMENTAL

Berberine

Intervention Type: DRUG

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

Placebo

placebo (500 mg orally twice a day)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Berberine

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Food and Health Bureau, Hong Kong

OTHER_GOV

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jie Zhao, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Li Ka Shing Faculty of Medicine

Hong Kong, , Hong Kong

Countries

Hong Kong

References

Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049. Epub 2014 Dec 10.

Reference Type: BACKGROUND

PMID: 25498346 (View on PubMed)

Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008 Aug;22(8):999-1012. doi: 10.1002/ptr.2399.

Reference Type: BACKGROUND

PMID: 18618524 (View on PubMed)

Skarydova L, Hofman J, Chlebek J, Havrankova J, Kosanova K, Skarka A, Hostalkova A, Plucha T, Cahlikova L, Wsol V. Isoquinoline alkaloids as a novel type of AKR1C3 inhibitors. J Steroid Biochem Mol Biol. 2014 Sep;143:250-8. doi: 10.1016/j.jsbmb.2014.04.005. Epub 2014 Apr 24.

Reference Type: BACKGROUND

PMID: 24769118 (View on PubMed)

Other Identifiers

15162621

Identifier Type: -

Identifier Source: org_study_id