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

Study Overview
=================
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.

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

Conditions
-----------------
Metabolic Syndrome

Intervention / Treatment
-----------------
* Drug: Berberine
* Behavioral: Healthy lifestyle intervention


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Group<br>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<br>* 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.<br>|
| Experimental: Berberine Group<br>Berberine plus healthy lifestyle intervention. Berberine dose is 500mg twice daily and maintained until the last subject completes 3-year intervention. | Drug: Berberine<br>* 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<br>* Other names: berberine hydrochloride;Behavioral: Healthy lifestyle intervention<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Berberine, Cardiovascular Diseases, Diabetes, Metabolic Syndrome, Primary Prevention