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

Overview

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.

Interventions

• Drug Berberine
  The tablet of berberine and placebo are both coated with white sugar and had the same appearance. Berberine tablet will be orally taken with a dose of 500mg twice daily
• Behavioral Healthy lifestyle intervention
  Healthy lifestyle intervention will be launched according to the "Chinese guidelines on prevention of cardiovascular and metabolic diseases by Chinese Preventive Medical Association in 2019", including health lectures, health information promotion, health manual and so on.

Primary outcome measures

• Rate of composite cardiometabolic endpoints [Time frame: three year]

Secondary outcome measures (11)

• Rate of composite endpoints of cardiovascular diseases 1 [Time frame: three year]
• Rate of composite end point of cardiovascular disease 2 [Time frame: three year]
• Rates of each component of the composite end point [Time frame: three year]
• Rate of all-cause mortality [Time frame: three year]
• Rate of newly diagnosed prediabetes [Time frame: three year]
• Rate of newly diagnosed hypertension [Time frame: three year]
• Rate of newly diagnosed malignancy [Time frame: three year]
• Concentrations of serum lipid parameters [Time frame: three year]
• Changes of abdominal circumference [Time frame: three year]
• Changes of waist-hip ratio [Time frame: three year]
• Changes of body mass index [Time frame: three year]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

China · 1 center

• Peking University Third Hospital — Beijing

Publications

• 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 C PMID 30894319
• 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. PMID 15531889
• 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. PMID 25607236

Identifiers

NCT: NCT05105321 · CSCF2021A04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗