ABCD: Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: berberine group Berberine hydrochloride plus lifestyle intervention |
Drug: Berberine plus lifestyle intervention
berberine hydrochloride 500mg twice a day plus lifestyle intervention. Lifestyle intervention is based on"Chinese 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.
|
| Placebo Comparator: placebo group Placebo plus lifestyle intervention |
Behavioral: Placebo plus lifestyle intervention
Placebo with identical shape, colour, odour and taste twice a day plus lifestyle intervention. Lifestyle intervention is based on"Chinese 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Other Outcome Measures
- Change of depressive symptoms [1 year]
Measured by Patient Health Questionnaire-9 (PHQ-9)
- Time to the components of major cardiovascular events 1 [3 years]
Time to first occurrence of cardiovascular death
- Time to the components of major cardiovascular events 2 [3 years]
Time to first occurrence of fatal or non-fatal ischemic stroke
- Time to the components of major cardiovascular events 3 [3 years]
Time to first occurrence of fatal or non-fatal myocardial infarction
- Time to the components of major cardiovascular events 4 [3 years]
Time to first occurrence of angina with evidence of ischemia
- Time to the components of major cardiovascular events 5 [3 years]
Time to first occurrence of arterial revascularization (including coronary or non-coronary)
- Subgroup analysis 1 for primary outcome measure [3 years]
Age (<65, ≥65)
- Subgroup analysis 2 for primary outcome measure [3 years]
Sex (male, female)
- Subgroup analysis 3 for primary outcome measure [3 years]
Body mass index (<28kg/cm2, ≥28kg/cm2)
- Subgroup analysis 4 for primary outcome measure [3 years]
Type of prediabetes (isolated impaired fasting glucose [6.1 mmol/L≤FPG<7.0 mmol/L, 2hPG<7.8 mmol/L], isolated impaired glucose tolerance [FPG<6.1 mmol/L, 7.8mmol/L≤2hPG<11.1 mmol/L], impaired fasting glucose and impaired glucose tolerance [6.1 mmol/L≤FPG<7.0 mmol/L, 7.8mmol/L≤2hPG<11.1 mmol/L])
- Subgroup analysis 5 for primary outcome measure [3 years]
hypertension (yes, no)
- Subgroup analysis 6 for primary outcome measure [3 years]
Current smoker (yes, no)
- Subgroup analysis 7 for primary outcome measure [3 years]
Triglyceride (<1.7mmol/L, ≥1.7mmol/L)
- Subgroup analysis 8 for primary outcome measure [3 years]
HDL-C (<1.0mmol/L, ≥1.0mmol/L)
- Subgroup analysis 9 for primary outcome measure [3 years]
LDL-C (≤3.4mmol/L, >3.4mmol/L)
- Subgroup analysis 10 for primary outcome measure [3 years]
Family history of premature coronary heart disease (biological father's diagnosis of myocardial infarction, receipt of percutaneous coronary intervention, or coronary artery bypass grafting before 55 years-old, or biological mother's diagnosis of myocardial infarction, receipt of percutaneous coronary intervention, or coronary artery bypass grafting before 65 years-old)
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases | Beijing | China |
Sponsors and Collaborators
- China National Center for Cardiovascular Diseases
Investigators
- Principal Investigator: Jing Li, PhD, National Center for Cardiovascular Diseases
- Principal Investigator: Haibo Zhang, MD, National Center for Cardiovascular Diseases
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 2021-CXGC04-1