Effect of Berberine on Cardiovascular Disease Risk Factors: a Mechanistic Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- lipid profile
研究概览
简要总结
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a comprehensive systematic review and meta-analysis of 27 randomized controlled trials (RCTs), berberine effectively reduced low density lipoprotein cholesterol (LDL-c) (-0.65 mmol/L, 95% confidence interval (CI) -0.75 to -0.56), triglycerides (TG) (-0.39 mmol/L, 95% CI -0.59 to -0.19), total cholesterol (TC) (-0.66 mmol/L, 95% CI -1.02 to -0.31) and increased high density lipoprotein cholesterol (HDL-c) (0.07mmol/L, 95% CI 0.04 to 0.1).1 Notably, no serious adverse event has been reported in these trials,1 suggesting a good tolerability of berberine. The mechanism by which berberine exerts a protective role in atherosclerosis is unclear. Protoberberines have been identified as a new inhibitor of AKR1C3, an enzyme responsible for the regulation of steroid hormone action.3 The investigators propose to examine the effects of berberine on a set of well-established CVD risk factors including lipids, systolic and diastolic blood pressure, coagulation factors, adiposity, fasting glucose, insulin, and liver function, as well as to examine potential mediation via testosterone and/or sex hormone binding globulin using a mechanistic, randomized, double-blind, placebo-controlled trial in Chinese men with hyperlipidemia.
详细描述
Objectives: to assess the effect of berberine on a set of well-established CVD risk factors, including lipids, systolic and diastolic blood pressure, coagulation factors, fasting glucose, insulin, adiposity (body mass index (BMI) and waist-hip ratio (WHR)) and the mediation via testosterone and/or sex hormone binding globulin using a mechanistic, parallel RCT.
Study design: a mechanistic, randomized, double-blind, placebo-controlled, parallel trial in 84 Chinese men in Hong Kong.
Interventions: the eligible participants will be randomized to take berberine (500 mg orally twice a day) or placebo for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention.
Data analysis and expected results: the investigators will use an intention to treat analysis, with multiple imputation for missing data. The investigators will compare the baseline characteristics of participants in the two arms using analysis of variance. The investigators will assess the effects of berberine on changes in CVD risk factors using analysis of variance, and the mediation using causal mediation analysis. Compared to the placebo group, the participants receiving berberine are expected to have lower burden of cardiovascular disease risk factors at the end of the intervention. These effects may be mediated or partly mediated by lowering testosterone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men, who are
- •aged 20 to 65 years
- •of Chinese ethnicity
- •with hyperlipidemia, defined as TG greater than 150 mg/dl (1.70 mmol/L), TC greater than 200 mg/dl (5.16 mmol/L), and/or LDL-c greater than 100 mg/dl (2.58 mmol/L)
- •willing to make return visits
- •not currently receiving hormone replacement therapy, such as testosterone replacement therapy, in the past 12 months
- •not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month
- •free of any congenital diseases, including familial hypercholesterolemia
- •free of any infectious diseases, e.g. seasonal influenza
- •free of anemia and glucose-6-phosphate dehydrogenase deficiency
- •with no history of any chronic diseases including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders.
排除标准
- •All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent
研究组 & 干预措施
Berberine
berberine (500 mg orally twice a day)
干预措施: Berberine (Drug)
Placebo
placebo (500 mg orally twice a day)
干预措施: Placebo (Drug)
结局指标
主要结局
lipid profile
时间窗: change from baseline lipid profile at 12 weeks
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
waist hip ratio
时间窗: change from baseline waist hip ratio at 12 weeks
waist circumstance and hip circumstance will be combined to report waist hip ratio
fasting glucose
时间窗: change from baseline fasting glucose at 12 weeks
fasting glucose in mmol/L
fasting insulin
时间窗: change from baseline fasting insulin at 12 weeks
fasting insulin in mmol/L
liver function
时间窗: change from baseline fasting insulin at 12 weeks
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
sex hormone binding globulin (SHBG)
时间窗: change from baseline SHBG at 12 weeks
SHBG in nmol/L
thrombin time
时间窗: change from baseline thrombin time at 12 weeks
thrombin time in sec
blood pressure
时间窗: change from baseline blood pressure at 12 weeks
systolic blood pressure and diastolic blood pressure in mmHg
thromboxane A2
时间窗: change from baseline thromboxane A2 at 12 weeks
thromboxane A2 in mmol/L
testosterone
时间窗: change from baseline testosterone at 12 weeks
testosterone in mmol/L
body mass index (BMI)
时间窗: change from baseline body mass index at 12 weeks
weight and height will be combined to report BMI in kg/m\^2
次要结局
未报告次要终点