A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine

NCT03770325 | Completed Phase 2

• 1 other identifier: 15162621
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Risk Factor

Outcome Measures

Primary Outcomes (22)

• lipid profile

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

  change from baseline lipid profile at 8 weeks

• lipid profile

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

  change from baseline lipid profile at 12 weeks

• blood pressure

  systolic blood pressure and diastolic blood pressure in mmHg

  change from baseline blood pressure at 8 weeks

• blood pressure

  systolic blood pressure and diastolic blood pressure in mmHg

  change from baseline blood pressure at 12 weeks

• thromboxane A2

  thromboxane A2 in mmol/L

  change from baseline thromboxane A2 at 8 weeks

• thromboxane A2

  thromboxane A2 in mmol/L

  change from baseline thromboxane A2 at 12 weeks

• testosterone

  testosterone in mmol/L

  change from baseline testosterone at 8 weeks

• testosterone

  testosterone in mmol/L

  change from baseline testosterone at 12 weeks

• body mass index (BMI)

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

  change from baseline body mass index at 8 weeks

• body mass index (BMI)

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

  change from baseline body mass index at 12 weeks

• waist hip ratio

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

  change from baseline waist hip ratio at 8 weeks

• waist hip ratio

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

  change from baseline waist hip ratio at 12 weeks

• fasting glucose

  fasting glucose in mmol/L

  change from baseline fasting glucose at 8 weeks

• fasting glucose

  fasting glucose in mmol/L

  change from baseline fasting glucose at 12 weeks

• fasting insulin

  fasting insulin in mmol/L

  change from baseline fasting insulin at 8 weeks

• fasting insulin

  fasting insulin in mmol/L

  change from baseline fasting insulin at 12 weeks

• liver function

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

  change from baseline fasting insulin at 8 weeks

• liver function

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

  change from baseline fasting insulin at 12 weeks

• sex hormone binding globulin (SHBG)

  SHBG in nmol/L

  change from baseline SHBG at 8 weeks

• sex hormone binding globulin (SHBG)

  SHBG in nmol/L

  change from baseline SHBG at 12 weeks

• thrombin time

  thrombin time in sec

  change from baseline thrombin time at 8 weeks

• thrombin time

  thrombin time in sec

  change from baseline thrombin time at 12 weeks

Study Arms (2)

Berberine

EXPERIMENTAL

berberine (500 mg orally twice a day)

Drug: Berberine

Placebo

PLACEBO COMPARATOR

placebo (500 mg orally twice a day)

Drug: Placebo

Interventions

Berberine DRUG

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

Berberine

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Food and Health Bureau, Hong Kong: collaborator

Study Sites (1)

Li Ka Shing Faculty of Medicine

Hong Kong, Hong Kong

Location

Related Publications (3)

• 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.

  PMID: 25498346 BACKGROUND

• 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.

  PMID: 18618524 BACKGROUND

• 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.

  PMID: 24769118 BACKGROUND

MeSH Terms

Interventions

Berberine

Intervention Hierarchy (Ancestors)

Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jie Zhao, PhD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 10, 2018
• Study Start: April 1, 2019
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 4, 2020

Record last verified: 2020-11

Locations

HK (1)