Study on the Sex-specific, Lipid- and Lipoprotein-lowering Effects of Berberine

Assessing the Sex-specific, Lipid- and Lipoprotein-lowering Effects of Berberine Using Randomized, Placebo-controlled, Double-masked Trial

The goal of this clinical trial is to learn if berberine works to affect lipids and lipoproteins in Chinese females aged 20 to 65 years with hyperlipidaemia. The goal also includes to examine the sex-specific effect of berberine on lipids and lipoproteins. Our previous HMRF-funded randomized trial in men and prior evidence suggests berberine affects sex hormones. Given the different sex hormone profiles in men and women, the main question it aims to answer is:

• Does berberine have sex-specific lipid-modifying effects? Researchers will compare berberine to a placebo (a look-alike substance that contains no drug) to see if berberine works to affect lipids and lipoproteins.

Participants will:

• Take a baseline questionnaire
• Take berberine or a placebo every day for 12 weeks
• Take follow-up visits after 8 weeks and 12 weeks for blood sample collections and tests

Study Overview

• Status: Enrolling by invitation
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Berberine; Drug: Placebo

Detailed Description

The overall aim of the project is to assess the sex-specific effects of berberine on lipids, apoA1, apoB, and Lp(a). Specifically, the objectives of the project are to 1) assess the effect of berberine on lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, and TG), lipoproteins (apoA1, apoB, and Lp(a)) and sex hormones by conducting a randomized, parallel, double-masked, placebo-controlled trial of berberine RCT in women; 2) assess the effect of berberine on apoA1, apoB, Lp(a) and sex hormone binding globulin (SHBG) in men using stored samples from our completed RCT of berberine in men; 3) assess whether the effects of berberine on lipids, lipoproteins and sex hormones differ in men and women.

This is a randomized, parallel, double-blinded, placebo-controlled trial of berberine in 100 Chinese women with hyperlipidemia in Hong Kong.

Participants will be randomized to two arms in which half of the participants will receive berberine (500 mg orally twice a day) and the other half will receive placebos (500 mg orally twice a day) for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention.

The investigators will use an intention-to-treat analysis. Changes in lipids and lipoproteins after 8- and 12-week treatment will be assessed using analysis of variance and generalized estimating equation (GEE) model accounting for measurements at both time points.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • School of Public Health, The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women, 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), total cholesterol greater than 200 mg/dl (5.16 mmol/L), and/or LDL-cholesterol greater than 100 mg/dl (2.58 mmol/L).
  4. willing to make return visits.
  5. not currently receiving hormone replacement therapy or medications/pills containing hormones (such as hormonal contraception or hormone replacement therapy) in the past 12 months.
  6. not currently taking berberine or nutraceuticals that contain berberine.
  7. free of any congenital diseases, including familial hypercholesterolemia.
  8. free of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. G6PD will be tested using G6PD rapid diagnostic tests.
  9. free of hemolytic anemia.
  10. free of any infectious diseases, e.g., seasonal influenza.
  11. without liver/renal diseases.
  12. not pregnant or planning to get pregnant in the next three months. Pregnancy will be ruled out using HCG ULTRA pregnancy tests.
  13. not currently breastfeeding.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Berberine Group; berberine (500 mg orally twice a day)	Drug: Berberine; Participants will take purified berberine (500 mg orally twice a day) for 12 weeks.; Other Names: Berberine (500 mg orally twice a day)
Placebo Comparator: Placebo Group; placebo (500 mg orally twice a day)	Drug: Placebo; Participants will take placebo tablets, a look-alike substance that contains no drug, (500 mg orally twice a day) for 12 weeks.; Other Names: Placebo (500 mg orally twice a day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total cholesterol in mmol/L	Total cholesterol, LDL-cholesterol, TG, apoB, and Lp(a), which are causal factors for coronary heart disease.	4 months for biomarker assessment, 6 months for data analysis
LDL-cholesterol in mmol/L	Total cholesterol, LDL-cholesterol, TG, apoB, and Lp(a), which are causal factors for coronary heart disease.	4 months for biomarker assessment, 6 months for data analysis
Triglycerides in mmol/L	Total cholesterol, LDL-cholesterol, TG, apoB, and Lp(a), which are causal factors for coronary heart disease.	4 months for biomarker assessment, 6 months for data analysis
Apolipoprotein B in mg/dL	Total cholesterol, LDL-cholesterol, TG, apoB, and Lp(a), which are causal factors for coronary heart disease.	4 months for biomarker assessment, 6 months for data analysis
Lipoprotein (a) in mg/dL	Total cholesterol, LDL-cholesterol, TG, apoB, and Lp(a), which are causal factors for coronary heart disease.	4 months for biomarker assessment, 6 months for data analysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HDL-cholesterol in mmol/L	Other relevant lipids and lipoproteins.	4 months for biomarker assessment, 6 months for data analysis
Non-HDL-cholesterol in mmol/L	Other relevant lipids and lipoproteins.as liver and kidney function.	4 months for biomarker assessment, 6 months for data analysis
Apolipoprotein A1 in mg/dL	Other relevant lipids and lipoproteins.	4 months for biomarker assessment, 6 months for data analysis
Estradiol (E2) in pg/mL	Examine the sex-specific effects of berberine on apoA1, apoB, Lp(a) and lipids	4 months for biomarker assessment, 6 months for data analysis
Sex hormone binding globulin (SHBG) in nmol/L	Examine the sex-specific effects of berberine on apoA1, apoB, Lp(a) and lipids	4 months for biomarker assessment, 6 months for data analysis
Testosterone in ng/dL	Examine the sex-specific effects of berberine on apoA1, apoB, Lp(a) and lipids	4 months for biomarker assessment, 6 months for data analysis

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Jie Zhao, Dr, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Hyperlipidemia; lipid; Lp(a); berberine; apoB; lipoprotein; sex-hormones; apoA1
• Additional Relevant MeSH Terms: Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: 21222191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No