Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus

Hypertension Clinical Trial

— ABCD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05749874
• Other study ID #: 2021-CXGC04-1
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 1, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2023
• Source: China National Center for Cardiovascular Diseases
• Contact: Jing Li, PhD
• Phone: +86 60866077
• Email: jing.li[@]fwoxford.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6500
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Abdominal Obesity
• Cardiovascular Diseases
• Diabetes Mellitus
• Dyslipidemias
• Hypertension
• Obesity, Abdominal
• PreDiabetes

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.

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.

Locations

Country	Name	City	State
China	Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of depressive symptoms	Measured by Patient Health Questionnaire-9 (PHQ-9)	1 year
Other	Time to the components of major cardiovascular events 1	Time to first occurrence of cardiovascular death	3 years
Other	Time to the components of major cardiovascular events 2	Time to first occurrence of fatal or non-fatal ischemic stroke	3 years
Other	Time to the components of major cardiovascular events 3	Time to first occurrence of fatal or non-fatal myocardial infarction	3 years
Other	Time to the components of major cardiovascular events 4	Time to first occurrence of angina with evidence of ischemia	3 years
Other	Time to the components of major cardiovascular events 5	Time to first occurrence of arterial revascularization (including coronary or non-coronary)	3 years
Other	Subgroup analysis 1 for primary outcome measure	Age (<65, =65)	3 years
Other	Subgroup analysis 2 for primary outcome measure	Sex (male, female)	3 years
Other	Subgroup analysis 3 for primary outcome measure	Body mass index (<28kg/cm2, =28kg/cm2)	3 years
Other	Subgroup analysis 4 for primary outcome measure	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])	3 years
Other	Subgroup analysis 5 for primary outcome measure	hypertension (yes, no)	3 years
Other	Subgroup analysis 6 for primary outcome measure	Current smoker (yes, no)	3 years
Other	Subgroup analysis 7 for primary outcome measure	Triglyceride (<1.7mmol/L, =1.7mmol/L)	3 years
Other	Subgroup analysis 8 for primary outcome measure	HDL-C (<1.0mmol/L, =1.0mmol/L)	3 years
Other	Subgroup analysis 9 for primary outcome measure	LDL-C (=3.4mmol/L, >3.4mmol/L)	3 years
Other	Subgroup analysis 10 for primary outcome measure	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)	3 years
Primary	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	Time to new-onset diabetes	Diabetes is determined by oral glucose tolerance test, clinical diagnosis or use of glucose-lowering medications.	3 years
Secondary	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
Secondary	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
Secondary	Time to first occurrence of composite endpoint of major cardiovascular event 2	cardiovascular death, ischemic stroke and myocardial infarction	3 years
Secondary	Time to all-cause death	Death due to all causes	3 years
Secondary	Time to newly diagnosed cancer	all events of cancer or classified by primary sites	3 years