Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus

Study Overview
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Brief Summary
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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
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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.

Official Title
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Assess the Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus Among Individuals With High Cardiometabolic Risk

Conditions
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PreDiabetes, Abdominal Obesity, Hypertension, Dyslipidemias

Intervention / Treatment
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* Drug: Berberine plus lifestyle intervention
* Behavioral: Placebo plus lifestyle intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: berberine group<br>Berberine hydrochloride plus lifestyle intervention | Drug: Berberine plus lifestyle intervention<br>* berberine hydrochloride 500mg twice a day plus lifestyle intervention. Lifestyle intervention is based onChinese guideline on the primary prevention of cardiovascular diseases and Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition), including health education on smoking, alcohol consumption, diet, physical activity and weight loss, etc.<br>|
| Placebo Comparator: placebo group<br>Placebo plus lifestyle intervention | Behavioral: Placebo plus lifestyle intervention<br>* Placebo with identical shape, colour, odour and taste twice a day plus lifestyle intervention. Lifestyle intervention is based onChinese guideline on the primary prevention of cardiovascular diseases and Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition), including health education on smoking, alcohol consumption, diet, physical activity and weight loss, etc.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to new-onset diabetes | Diabetes is determined by oral glucose tolerance test, clinical diagnosis or use of glucose-lowering medications. | 3 years | 
| Normalization of glucose parameters | 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%. | 3 years | 
| Time to first occurrence of composite endpoint of major cardiovascular event 1 | cardiovascular death, ischemic stroke, myocardial infarction, angina with evidence of ischemia, and arterial revascularization | 3 years | 
| Time to first occurrence of composite endpoint of major cardiovascular event 2 | cardiovascular death, ischemic stroke and myocardial infarction | 3 years | 
| Time to all-cause death | Death due to all causes | 3 years | 
| Time to newly diagnosed cancer | all events of cancer or classified by primary sites | 3 years |