Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus

NCT05749874 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 2021-CXGC04-1
• Study Type: interventional
• Target: 2,024
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, double-blinded, randomized controlled trial aims to evaluate the effect of berberine on preventing cardiovascular disease and diabetes mellitus among individuals with high cardiometabolic risk in China.

Conditions

PreDiabetes; Abdominal Obesity; Hypertension; Dyslipidemias; Atherosclerotic Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• The distribution of glycemic status at 1 year after randomization

  Categorized as normal glucose metabolism, prediabetes, and diabetes

  Intervention Period: 1 year

Secondary Outcomes (16)

• Changes of glycemic-related parameters

  Intervention Period: 1 year

• Changes of lipid-related parameters

  Intervention Period: 1 year

• Change of inflammation-related marker

  Intervention Period: 1 year

• Change of physical examination measures

  Intervention Period: 1 year

• Changes of other parameters

  Intervention Period: 1 year

Other Outcomes (10)

• Subgroup analysis 1 for primary outcome measure

  Intervention Period: 1 year

• Subgroup analysis 2 for primary outcome measure

  Intervention Period: 1 year

• Subgroup analysis 3 for primary outcome measure

  Intervention Period: 1 year

Study Arms (2)

berberine group

EXPERIMENTAL

Berberine hydrochloride plus lifestyle intervention

Drug: Berberine plus lifestyle intervention

placebo group

PLACEBO COMPARATOR

Placebo plus lifestyle intervention

Behavioral: Placebo plus lifestyle intervention

Interventions

Berberine plus lifestyle intervention DRUG

berberine hydrochloride 500mg twice a day plus lifestyle intervention. Lifestyle intervention is based on Chinese guideline for primary prevention of cardiovascular diseases, and Chinese guideline for management of type 2 diabetes mellitus, coronary heart disease, myocardial infarction and stroke. Intervention includes health education on smoking, alcohol consumption, diet, physical activity and weight loss, etc.

berberine group

Placebo plus lifestyle intervention BEHAVIORAL

Placebo with identical shape, colour, odour and taste twice a day plus lifestyle intervention. Lifestyle intervention is based on Chinese guideline for primary prevention of cardiovascular diseases, and Chinese guideline for management of type 2 diabetes mellitus, coronary heart disease, myocardial infarction and stroke. Intervention includes health education on smoking, alcohol consumption, diet, physical activity and weight loss, etc.

placebo group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged ≥40 years old
• Participants with prediabetes, defined as glycated hemoglobin (HbA1c) between 5.7% and 6.4%
• Participants with body mass index\>25kg/m2, or abdominal obesity (i.e., waist circumference ≥85 cm in female or waist circumference ≥90 cm in male)
• Participants with established atherosclerosis cardiovascular diseases (ASCVD), or with at least two cardiovascular risk factors: (a) hypertension (b) aged ≥45(male) / 55 (female), (c) current smoker, (d) HDL-C\<1mmol/L or TG≥2.3mmol/L
• Participants with established ASCVD required LDL-C≤70 mg/dL (1.8mmol/L) for participants with ASCVD or receiving optimized LDL-C-lowering therapy (at least moderate-intensity statin therapy, unless contraindicated or intolerant)

You may not qualify if:

• Participants with FPG≥7.0 mmol/L, diagnosed with diabetes or taking oral glucose-lowering drugs
• Participants diagnosed with acute coronary syndrome, stroke, transient ischemic attack, or undergoing cardiac surgery or cardiac intervention (i.e., implantation of cardiac closure devices, cardiac resynchronization therapy, or catheter ablation), percutaneous coronary intervention or valvuloplasty/other cardiac valve repair or implantation surgery within the 3 months before randomization
• Participants who plan to perform coronary and/or non coronary revascularization surgery, or cardiac surgery within 6 months after randomization
• Participants diagnosed with heart failure or left ventricular ejection fraction\<40%, severe cardiac valvular disease, cardiomyopathy, congenital heart disease
• Conditions known to interfere with the accuracy of HbA1c measurement, including rheumatoid arthritis, hemolytic anemia, aplastic anemia, hemoglobinopathies, splenomegaly, splenectomy, vitamin B12 deficiency, alcoholism, long-term high-dose aspirin use, or chronic use of anesthetics or hydroxyurea
• Recipients of major organ transplants (e.g., lung, liver, heart, bone marrow, kidneys, etc.)
• Participants diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Participants taking berberine or drug containing berberine in the past 1 month
• Participants with any adverse reaction to berberine
• Participants with severe constipation, diarrhea, and/or severe chronic intestinal diseases (e.g., ulcerative colitis, Crohn's disease, irritable bowel syndrome, etc.)
• Participants who plan to have weight loss surgery, plan to take or currently taking drugs for weight loss
• Participants with active liver diseases, or alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \> 3 times upper limit of normal
• Estimated glomerular filtration rate (eGFR) \< 45 ml/(min×1.73m2)
• Women who are pregnant or breastfeeding, or those who plan to be pregnant during the trial
• Participants with malignant tumors, or other serious diseases with life expectancy of less than 3 years

Sponsors & Collaborators

• China National Center for Cardiovascular Diseases: lead

Study Sites (1)

Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases

Beijing, China

Location

Related Publications (2)

• Kong WJ, Vernieri C, Foiani M, Jiang JD. Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders. Pharmacol Ther. 2020 May;209:107496. doi: 10.1016/j.pharmthera.2020.107496. Epub 2020 Jan 27.

  PMID: 32001311 BACKGROUND

• Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004 Dec;10(12):1344-51. doi: 10.1038/nm1135. Epub 2004 Nov 7.

  PMID: 15531889 BACKGROUND

MeSH Terms

Conditions

Prediabetic State; Obesity, Abdominal; Hypertension; Dyslipidemias; Atherosclerosis

Interventions

Berberine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jing Li, PhD

  National Center for Cardiovascular Diseases

  PRINCIPAL INVESTIGATOR

• Haibo Zhang, MD

  National Center for Cardiovascular Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2023
• First Posted: March 1, 2023
• Study Start: October 31, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

CN (1)