Cardiovascular Diseases and Diabetes Prevention Programme in Metabolic Syndrome (CDPP) (CDPP)

Efficacy and Safety of Berberine on Primary Prevention of Cardiovascular Diseases and Diabetes in Metabolic Syndrome: a Randomized, Controlled Trial

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Behavioral: Healthy lifestyle intervention; Drug: Berberine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 5200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wenyao Wang, MD, PhD; Phone Number: 0086-18810488381; Email: wwypumc@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
      • Contact: Wenyao Wang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group; Placebo plus healthy lifestyle intervention. Placebo with same appearance of berberine tablet will be orally taken twice daily and maintained until the last subject completes 3-year intervention.	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.
Experimental: Berberine Group; Berberine plus healthy lifestyle intervention. Berberine dose is 500mg twice daily and maintained until the last subject completes 3-year intervention.	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.; 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; Other Names: berberine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of composite cardiometabolic endpoints	The composite endpoints including cardiac death, nonfatal myocardial infarction, nonfatal stroke, and newly-diagnosed type 2 diabetes.	three year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of composite endpoints of cardiovascular diseases 1	The composite endpoints including cardiac death, nonfatal myocardial infarction, nonfatal stroke.	three year
Rate of composite end point of cardiovascular disease 2	The composite endpoints including cardiac death, nonfatal myocardial infarction, nonfatal stroke, successful resuscitation of cardiac arrest, heart failure, arterial revascularization.	three year
Rates of each component of the composite end point	Each component of the composite end point	three year
Rate of all-cause mortality	Death due to all causes.	three year
Rate of newly diagnosed prediabetes	Prediabetes including impaired fasting glucose and abnormal glucose tolerance.	three year
Rate of newly diagnosed hypertension	Hypertension is defined as blood pressure≥140/90 millimeters of mercury measured twice at not same day.	three year
Rate of newly diagnosed malignancy	Newly diagnosed malignancy.	three year
Concentrations of serum lipid parameters	Serum lipid parameters including total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, Lp(a).	three year
Changes of abdominal circumference	Measurement of abdominal circumference in centimeter	three year
Changes of waist-hip ratio	Measurement of waist-hip ratio	three year
Changes of body mass index	Measurement of body mass index in kg/m^2	three year

Collaborators and Investigators

• Sponsor: Tang Yida
• Collaborators: Chinese Society of Cardiology
• Investigators: Principal Investigator: Yi-Da Tang, MD, PhD, Peking University Third Hospital

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: J Am Coll Cardiol. 2019 Sep 10;74(10):1428-1429. J Am Coll Cardiol. 2020 Feb 25;75(7):840.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): December 1, 2028

Study Registration Dates

• First Submitted: October 16, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: November 1, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes; Cardiovascular Diseases; Metabolic Syndrome; Berberine; Primary Prevention
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Cardiovascular Diseases; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: CSCF2021A04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data, analytic methods, and study materials will not be made available immediately to other researchers. The reason for the lack of availability is that we have signed an agreement with the sponsor to restrict approach to study data, and the access must be agreed by both investigator and sponsor. Request to get these materials can be sent to the corresponding author, and we will provide them to vetted and qualified applicants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No