Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus

Phase 4

Not yet recruiting

• Conditions: Abdominal Obesity; PreDiabetes; Hypertension; Dyslipidemias
• Interventions: Drug: Berberine plus lifestyle intervention; Behavioral: Placebo plus lifestyle intervention

• Registration Number: NCT05749874
• Lead Sponsor: China National Center for Cardiovascular Diseases

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.

Detailed Description

The trial aims to evaluate the efficacy and safety of berberine treatment for individuals with high cardiometabolic risk. Potential eligible patients will be recruited from about 100 medical centers in China. After a 4-to-6-week run-in period with berberine, all the eligible participants will be randomized (1:1) to berberine 500mg twice a day plus lifestyle intervention (Arm A) or placebo plus lifestyle intervention (Arm B). The participants will be followed up at month 3 and month 6, and once every 3 months thereafter, and be followed up for 3 years.

Study Timeline

• Study First Submitted: 2023-02-20
• Study First Submitted QC: 2023-02-20
• Status Verified: 2023-03
• Study First Posted: 2023-03-01
• Last Update Submitted: 2023-03-06
• Last Update Posted: 2023-03-08
• Study Start: 2023-04-01
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6500

Inclusion Criteria

• Participants aged ≥45 years (male) or 55 years (female)
• Participants with abdominal obesity (i.e., waist circumference ≥85 cm in female or waist circumference ≥90 cm in male)
• Participants with prediabetes, defined as: (a) impaired fasting glucose (IFG) (i.e., 6.1 mmol/L≤FPG<7.0 mmol/L), or (b) impaired glucose tolerance (IGT) (i.e., 7.8mmol/L≤2hPG<11.1 mmol/L)
• Participants who meet at least two of four criteria: (a) hypertension, (b) current smoker, (c) HDL-C<1mmol/L and/or TG≥1.7mmol/L, (d) family history of premature coronary heart disease

Exclusion Criteria

• Patients with established atherosclerotic cardiovascular disease, including coronary heart disease, ischemic stroke, and peripheral atherosclerotic diseases
• Patients diagnosed with diabetes or taking oral glucose-lowering drugs
• Patients diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients taking berberine or drug containing berberine in the past 1 month
• Patients with any adverse reaction to berberine
• Patients with severe constipation, diarrhea, and/or severe chronic intestinal diseases (e.g., ulcerative colitis, Crohn's disease, irritable bowel syndrome, etc.)
• Patients who plan to have weight loss surgery, or are currently taking drugs for weight loss
• Patients 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
• Patients with malignant tumors, or other serious diseases with life expectancy of less than 3 years
• Patients with mental disorders, cognitive disorders, or other serious diseases that could affect study participation
• Patients who participated or have been participating other trials during the last 3 months
• Any other conditions that may hinder the compliance to the study intervention or follow-up visit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
berberine group	Berberine plus lifestyle intervention	Berberine hydrochloride plus lifestyle intervention
placebo group	Placebo plus lifestyle intervention	Placebo plus lifestyle intervention

Primary Outcome Measures

Name	Time	Method
Time to first occurrence of composite endpoint of new-onset diabetes and major cardiovascular events.	3 years	composite endpoint includes new-onset diabetes, cardiovascular death, ischemic stroke, myocardial infarction, angina with evidence of ischemia, and arterial revascularization

Secondary Outcome Measures

Name	Time	Method
Time to new-onset diabetes	3 years	Diabetes is determined by oral glucose tolerance test, clinical diagnosis or use of glucose-lowering medications.
Normalization of glucose parameters	3 years	Meeting all three criteria: 1) Fasting plasma glucose (FPG)\<6.1 mmol/L; 2) 2-hour postprandial blood glucose (2hPG)\<7.8 mmol/L; 3) HbA1c\<5.7%.
Time to first occurrence of composite endpoint of major cardiovascular event 1	3 years	cardiovascular death, ischemic stroke, myocardial infarction, angina with evidence of ischemia, and arterial revascularization
Time to first occurrence of composite endpoint of major cardiovascular event 2	3 years	cardiovascular death, ischemic stroke and myocardial infarction
Time to all-cause death	3 years	Death due to all causes
Time to newly diagnosed cancer	3 years	all events of cancer or classified by primary sites

Trial Locations

Locations (1)

Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases; 🇨🇳 Beijing, China