Back to resultsEffects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus (ABCD)
Primary Purpose
PreDiabetes, Abdominal Obesity, Hypertension
Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Berberine plus lifestyle intervention
Placebo plus lifestyle intervention
Sponsored by
About this trial
This is an interventional treatment trial for PreDiabetes
Eligibility 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
Sites / Locations
- Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
berberine group
placebo group
Arm Description
Berberine hydrochloride plus lifestyle intervention
Placebo plus lifestyle intervention
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Time to new-onset diabetes
Diabetes is determined by oral glucose tolerance test, clinical diagnosis or use of glucose-lowering medications.
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%.
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
Time to first occurrence of composite endpoint of major cardiovascular event 2
cardiovascular death, ischemic stroke and myocardial infarction
Time to all-cause death
Death due to all causes
Time to newly diagnosed cancer
all events of cancer or classified by primary sites
Full Information
NCT ID
NCT05749874
First Posted
February 20, 2023
Last Updated
March 6, 2023
Sponsor
China National Center for Cardiovascular Diseases
1. Study Identification
Unique Protocol Identification Number
NCT05749874
Brief Title
Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
Acronym
ABCD
Official Title
Assess the Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus Among Individuals With High Cardiometabolic Risk
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
China National Center for Cardiovascular Diseases
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PreDiabetes, Abdominal Obesity, Hypertension, Dyslipidemias
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
6500 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
berberine group
Arm Type
Experimental
Arm Description
Berberine hydrochloride plus lifestyle intervention
Arm Title
placebo group
Arm Type
Placebo Comparator
Arm Description
Placebo plus lifestyle intervention
Intervention Type
Drug
Intervention Name(s)
Berberine plus lifestyle intervention
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Placebo plus lifestyle intervention
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to first occurrence of composite endpoint of new-onset diabetes and major cardiovascular events.
Description
composite endpoint includes new-onset diabetes, cardiovascular death, ischemic stroke, myocardial infarction, angina with evidence of ischemia, and arterial revascularization
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Time to new-onset diabetes
Description
Diabetes is determined by oral glucose tolerance test, clinical diagnosis or use of glucose-lowering medications.
Time Frame
3 years
Title
Normalization of glucose parameters
Description
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 Frame
3 years
Title
Time to first occurrence of composite endpoint of major cardiovascular event 1
Description
cardiovascular death, ischemic stroke, myocardial infarction, angina with evidence of ischemia, and arterial revascularization
Time Frame
3 years
Title
Time to first occurrence of composite endpoint of major cardiovascular event 2
Description
cardiovascular death, ischemic stroke and myocardial infarction
Time Frame
3 years
Title
Time to all-cause death
Description
Death due to all causes
Time Frame
3 years
Title
Time to newly diagnosed cancer
Description
all events of cancer or classified by primary sites
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Change of depressive symptoms
Description
Measured by Patient Health Questionnaire-9 (PHQ-9)
Time Frame
1 year
Title
Time to the components of major cardiovascular events 1
Description
Time to first occurrence of cardiovascular death
Time Frame
3 years
Title
Time to the components of major cardiovascular events 2
Description
Time to first occurrence of fatal or non-fatal ischemic stroke
Time Frame
3 years
Title
Time to the components of major cardiovascular events 3
Description
Time to first occurrence of fatal or non-fatal myocardial infarction
Time Frame
3 years
Title
Time to the components of major cardiovascular events 4
Description
Time to first occurrence of angina with evidence of ischemia
Time Frame
3 years
Title
Time to the components of major cardiovascular events 5
Description
Time to first occurrence of arterial revascularization (including coronary or non-coronary)
Time Frame
3 years
Title
Subgroup analysis 1 for primary outcome measure
Description
Age (<65, ≥65)
Time Frame
3 years
Title
Subgroup analysis 2 for primary outcome measure
Description
Sex (male, female)
Time Frame
3 years
Title
Subgroup analysis 3 for primary outcome measure
Description
Body mass index (<28kg/cm2, ≥28kg/cm2)
Time Frame
3 years
Title
Subgroup analysis 4 for primary outcome measure
Description
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])
Time Frame
3 years
Title
Subgroup analysis 5 for primary outcome measure
Description
hypertension (yes, no)
Time Frame
3 years
Title
Subgroup analysis 6 for primary outcome measure
Description
Current smoker (yes, no)
Time Frame
3 years
Title
Subgroup analysis 7 for primary outcome measure
Description
Triglyceride (<1.7mmol/L, ≥1.7mmol/L)
Time Frame
3 years
Title
Subgroup analysis 8 for primary outcome measure
Description
HDL-C (<1.0mmol/L, ≥1.0mmol/L)
Time Frame
3 years
Title
Subgroup analysis 9 for primary outcome measure
Description
LDL-C (≤3.4mmol/L, >3.4mmol/L)
Time Frame
3 years
Title
Subgroup analysis 10 for primary outcome measure
Description
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)
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Li, PhD
Phone
+86 60866077
Email
jing.li@fwoxford.org
First Name & Middle Initial & Last Name or Official Title & Degree
Bin Wang, PhD
Phone
+86 60866220
Email
bin.wang@fuwai.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Li, PhD
Organizational Affiliation
National Center for Cardiovascular Diseases
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haibo Zhang, MD
Organizational Affiliation
National Center for Cardiovascular Diseases
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
City
Beijing
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Li, PhD
Phone
+86 60866077
Email
jing.li@fwoxford.org
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing 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.
Citations:
PubMed Identifier
32001311
Citation
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.
Results Reference
background
PubMed Identifier
15531889
Citation
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.
Results Reference
background
Learn more about this trial
Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
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