Clinical trial NCT05749874: Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
Official title: Assess the Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus Among Individuals With High Cardiometabolic Risk
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: PreDiabetes
Abdominal Obesity
Hypertension
Dyslipidemias
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2023-03-01
Enrollment: 6500
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to first occurrence of composite endpoint of new-onset diabetes and major cardiovascular events.
timeFrame: 3 years
Secondary outcomes:
measure: Time to new-onset diabetes
timeFrame: 3 years
measure: Normalization of glucose parameters
timeFrame: 3 years
measure: Time to first occurrence of composite endpoint of major cardiovascular event 1
timeFrame: 3 years
measure: Time to first occurrence of composite endpoint of major cardiovascular event 2
timeFrame: 3 years
measure: Time to all-cause death
timeFrame: 3 years
measure: Time to newly diagnosed cancer
timeFrame: 3 years
Other outcomes:
measure: Change of depressive symptoms
timeFrame: 1 year
measure: Time to the components of major cardiovascular events 1
timeFrame: 3 years
measure: Time to the components of major cardiovascular events 2
timeFrame: 3 years
measure: Time to the components of major cardiovascular events 3
timeFrame: 3 years
measure: Time to the components of major cardiovascular events 4
timeFrame: 3 years
measure: Time to the components of major cardiovascular events 5
timeFrame: 3 years
measure: Subgroup analysis 1 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 2 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 3 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 4 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 5 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 6 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 7 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 8 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 9 for primary outcome measure
timeFrame: 3 years
measure: Subgroup analysis 10 for primary outcome measure
timeFrame: 3 years
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
Study officials:
affiliation: National Center for Cardiovascular Diseases
name: Jing Li, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Center for Cardiovascular Diseases
name: Haibo Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.