Clinical trial NCT05105321: Cardiovascular Diseases and Diabetes Prevention Programme in Metabolic Syndrome (CDPP)
Official title: Efficacy and Safety of Berberine on Primary Prevention of Cardiovascular Diseases and Diabetes in Metabolic Syndrome: a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Metabolic Syndrome
Keywords: Berberine
Cardiovascular Diseases
Diabetes
Metabolic Syndrome
Primary Prevention
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Chinese Society of Cardiology
First posted: 2021-11-03
Enrollment: 5200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The metabolic syndrome population is at high-risk of cardiovascular diseases and diabetes. How to effectively control the risk factors of this population is the key to primary prevention of cardiovascular diseases and diabetes in China. This study aims to explore the efficacy and safety of an intervention strategy with berberine that can effectively treat a variety of risk factors (hyperglycemia, dyslipidemia, hypertension).

Detailed description: Metabolic syndrome (MS) is a condition with multiple abnormal metabolic components, including obesity, dysglycemia, dyslipidemia and hypertension. The components of metabolic syndrome are major risk factors for cardiovascular disease and diabetes. Cardiovascular disease (CVD) is the primary cause of death and disease burden in China. This study aims to explore an intervention drug that can effectively control a variety of risk factors (hyperglycemia, dyslipidemia, hypertension), so as to improve the effectiveness and practical feasibility of primary prevention. Berberine is a drug with multiple function. Basic studies and previous clinical studies suggest that it has definite regulatory effects on blood glucose, lipid levels and blood pressure with few adverse reactions. This study selected pleiotropic Berberine as a means of intervention. It would provide new thought and high-level evidence for the primary prevention of cardiovascular disease and diabetes in Chinese population.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with metabolic syndrome aged 40-75 years old.
* Metabolic syndrome was defined according to the Chinese Guidelines for the Prevention and Treatment of Dyslipidemia in Adults (revised edition 2016). Subjects will be diagnosed with metabolic syndrome when meeting three or more of the following items: 1, central obesity and/or abdominal obesity (waist circumference ≥90cm for men and ≥ 85cm for women); 2, hyperglycemia (fasting blood glucose ≥6.10 mmol/L or two-hour blood glucose ≥7.80 mmol/L in glucose tolerance test); 3, hypertension: blood pressure ≥130/85 mmHg and/or diagnosed hypertension under treatment; 4, fasting triglyceride ≥1.7 mmol/L (150mg/dl); 5, fasting HDL cholesterol\<1.0 mmol/L.

Exclusion Criteria:

* Previously diagnosed diabetes.
* Baseline LDL cholesterol≥130mg/dl (3.4mmol/L).
* Baseline triglyceride≥500mg/dl (5.6mmol/L).
* Baseline blood pressure ≥140/90 mmHg (twice not on the same day).
* Impaired liver function, have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, alanine/aspartate aminotransferase levels \>3 times the upper limit of the reference range at the screening visit.
* Renal dysfunction (glomerular filtration rate\<45ml/min)
* Patients ventilated by ventilator.
* Hypersensitivity to berberine.
* Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic respiratory disease).
* Severe chronic gastrointestinal disease.
* Severe psychiatric illness.
* Cancer requiring treatment in past 5 years.
* Women who are pregnant or breastfeeding .
* Participation in another clinical trial within the past 30 days .
* Other significant disease that in the Investigator's opinion would exclude the subject from the trial.

Primary outcomes:
measure: Rate of composite cardiometabolic endpoints
timeFrame: three year
Secondary outcomes:
measure: Rate of composite endpoints of cardiovascular diseases 1
timeFrame: three year
measure: Rate of composite end point of cardiovascular disease 2
timeFrame: three year
measure: Rates of each component of the composite end point
timeFrame: three year
measure: Rate of all-cause mortality
timeFrame: three year
measure: Rate of newly diagnosed prediabetes
timeFrame: three year
measure: Rate of newly diagnosed hypertension
timeFrame: three year
measure: Rate of newly diagnosed malignancy
timeFrame: three year
measure: Concentrations of serum lipid parameters
timeFrame: three year
measure: Changes of abdominal circumference
timeFrame: three year
measure: Changes of waist-hip ratio
timeFrame: three year
measure: Changes of body mass index
timeFrame: three year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
Study officials:
affiliation: Peking University Third Hospital
name: Yi-Da Tang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Sep 10;74(10):1376-1414. doi: 10.1016/j.jacc.2019.03.009. Epub 2019 Mar 17.
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.
citation: Chang W, Chen L, Hatch GM. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochem Cell Biol. 2015 Oct;93(5):479-86. doi: 10.1139/bcb-2014-0107. Epub 2014 Dec 1.