Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus (ABCD)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Dyslipidemias; PreDiabetes; Abdominal Obesity
• Intervention / Treatment: Drug: Berberine plus lifestyle intervention; Behavioral: Placebo plus lifestyle intervention

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 Type: Interventional
• Enrollment (Anticipated): 6500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Li, PhD; Phone Number: +86 60866077; Email: jing.li@fwoxford.org
• Study Contact Backup: Name: Bin Wang, PhD; Phone Number: +86 60866220; Email: bin.wang@fuwai.com

Study Locations

• China
  • Beijing, China
    • Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
    • Contact: Jing Li, PhD; Phone Number: +86 60866077; Email: jing.li@fwoxford.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 death of 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of depressive symptoms	Measured by Patient Health Questionnaire-9 (PHQ-9)	1 year
Time to the components of major cardiovascular events 1	Time to first occurrence of cardiovascular death	3 years
Time to the components of major cardiovascular events 2	Time to first occurrence of fatal or non-fatal ischemic stroke	3 years
Time to the components of major cardiovascular events 3	Time to first occurrence of fatal or non-fatal myocardial infarction	3 years
Time to the components of major cardiovascular events 4	Time to first occurrence of angina with evidence of ischemia	3 years
Time to the components of major cardiovascular events 5	Time to first occurrence of arterial revascularization (including coronary or non-coronary)	3 years
Subgroup analysis 1 for primary outcome measure	Age (<65, ≥65)	3 years
Subgroup analysis 2 for primary outcome measure	Sex (male, female)	3 years
Subgroup analysis 3 for primary outcome measure	Body mass index (<28kg/cm2, ≥28kg/cm2)	3 years
Subgroup analysis 4 for primary outcome measure	Type of prediabetes (isolated impaired fasting glucose, isolated impaired glucose tolerance, impaired fasting glucose and impaired glucose tolerance)	3 years
Subgroup analysis 5 for primary outcome measure	hypertension (yes, no)	3 years
Subgroup analysis 6 for primary outcome measure	Current smoker (yes, no)	3 years
Subgroup analysis 7 for primary outcome measure	Triglyceride (<1.7mmol/L, ≥1.7mmol/L)	3 years
Subgroup analysis 8 for primary outcome measure	HDL-C (<1.0mmol/L, ≥1.0mmol/L)	3 years
Subgroup analysis 9 for primary outcome measure	LDL-C (≤3.4mmol/L, >3.4mmol/L)	3 years
Subgroup analysis 10 for primary outcome measure	Family history of premature death of coronary heart disease	3 years

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Lipid Metabolism Disorders; Obesity; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Obesity, Abdominal
• Other Study ID Numbers: 2021-CXGC04-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: All the IPD that underlie results in the publication with study protocol and SAP will be shared to the public on the study website upon request with a protocol after approval from the ABCD steering committee. The access criteria and URL of the study website is not established yet.

Drug and device information, study documents

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