Rho-kinase in Patients With Atherosclerosis: Effects of Statins A Randomized Clinical Trial Comparing Ezetimibe/Simvastatin and Simvastatin
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- changes in the lipid profile change and Rho-kinase expression and activity
研究概览
简要总结
Multiple clinical trials, using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), have shown benefit in the primary and secondary prevention of atherosclerotic complications. However, till now, there is an incomplete understanding of all the mechanisms of the biologic effects of statins beyond LDL cholesterol (LDL-C) reduction, but there is accumulating evidence that the Rho-GTP/Rho-Kinase pathway (Rho/Rho-K) plays an important role and may be a strategic therapeutic target in cardiovascular diseases. With similar LDL-C reduction ability, the availability of Ezetimibe offers the potential to begin to address the question whether some of the benefits conferred by statins may accrue independently of their effects on LDL-C lowering. A better understanding of the role of the Rho/Rho-kinase signaling pathway in the pathogenesis of atherosclerosis in human is essential. Inhibition of Rho/Rho-kinase by statins may explain some of the biological beneficial effects of statins observed in clinical trials. This study aims to translate into patients important experimental discoveries regarding the initiation of inflammation in atherosclerosis in an attempt to improve upon the present treatment of cardiovascular diseases.
详细描述
Study Design:
A single-blind controlled trial with two arms will be conducted at National Chen-Kung University Hospital (NCKUH). We will screen subjects with stable atherosclerosis to complete enrollment of 40 subjects in the study (see inclusion and exclusion criteria section below). A central pharmacist at NCKUH will randomize the patients to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) for 28 days. If the patient is already on a statin a two-week washout period will be 2 weeks prior to trial initiation.
Primary Outcomes and measurement:
The primary outcomes are the mean changes in the Rho-kinase expression and activity in leukocytes in response to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) over 28 days.
Secondary Outcomes and measurement:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Male or female subjects aged 40 to 80 years
- •Documented stable atherosclerosis by angiography or vascular ultrasound (more that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program (ATP)-III guidelines)
- •LDL-cholesterol >100mg/dL (indication to treat with statin)
- •Written informed consent
- •Primary care physician authorization letter to participate in the study.
- •Exclusion criteria:
- •Inability to give consent
- •Pre-menopausal women
- •Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
- •History of LFT >2 times the upper normal limit
- •History of myopathy / myositis or CPK > 10 times the upper normal limit
- •CPK above normal limits at study onset
- •Any evidence of inflammatory, infectious or neoplastic disease
- •History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.
排除标准
- 未提供
研究组 & 干预措施
high dose statin
40mg of Simvastatin (n=20)
干预措施: Simvastatin (Zocor) (Drug)
combination arm
10mg/10mg of Ezetimibe/Simvastatin (n=20)
干预措施: 10mg/10mg of Ezetimibe/Simvastatin (Vytorin) (Drug)
结局指标
主要结局
changes in the lipid profile change and Rho-kinase expression and activity
时间窗: 28 days
次要结局
- correlation between changes in Rho-kinase expression and activity with the changes in LDL-C, hsCRP and BAFMD(28 days)