A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Berberine berberine (500 mg orally twice a day) |
Drug: Berberine
Purified berberine (500 mg orally twice a day) in tablets for 12 weeks
|
| Placebo Comparator: Placebo placebo (500 mg orally twice a day) |
Drug: Placebo
Placebo tablets, prepared with the same appearance, for 12 weeks
|
Outcome Measures
Primary Outcome Measures
- lipid profile [change from baseline lipid profile at 8 weeks]
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
- 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 8 weeks]
systolic blood pressure and diastolic blood pressure in mmHg
- 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 8 weeks]
thromboxane A2 in mmol/L
- thromboxane A2 [change from baseline thromboxane A2 at 12 weeks]
thromboxane A2 in mmol/L
- testosterone [change from baseline testosterone at 8 weeks]
testosterone 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 8 weeks]
weight and height will be combined to report BMI in kg/m^2
- 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
- waist hip ratio [change from baseline waist hip ratio at 8 weeks]
waist circumstance and hip circumstance will be combined to report waist hip ratio
- 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 8 weeks]
fasting glucose in mmol/L
- fasting glucose [change from baseline fasting glucose at 12 weeks]
fasting glucose in mmol/L
- fasting insulin [change from baseline fasting insulin at 8 weeks]
fasting insulin 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 8 weeks]
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin 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 8 weeks]
SHBG in nmol/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 8 weeks]
thrombin time in sec
- thrombin time [change from baseline thrombin time at 12 weeks]
thrombin time in sec
Eligibility Criteria
Criteria
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
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not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month
-
free of any congenital diseases, including familial hypercholesterolemia
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Li Ka Shing Faculty of Medicine | Hong Kong | Hong Kong |
Sponsors and Collaborators
- The University of Hong Kong
- Food and Health Bureau, Hong Kong
Investigators
- Principal Investigator: Jie Zhao, PhD, The University of Hong Kong
Study Documents (Full-Text)
None provided.More Information
Publications
- 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. Review.
- 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. Review.
- 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.
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