Phase 4 Study of Clopidogrel in Patients With Stable Coronary Artery Disease to Determine Effects on Vascular Function, Biomarkers and Endothelial Progrenitor Cells
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Nitroglycerin-mediated Vasodilation
研究概览
简要总结
The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.
详细描述
Blockages in the blood vessels of the heart are caused by atherosclerosis. Atherosclerosis is the main cause for chest pain and heart attacks. Gradual narrowing of the vessels of the heart caused by blockages causes chronic symptoms, such as chest pain. Those with these findings often have a cardiac catheterization to detect these blockages. Additionally these patients may have an angioplasty or stent placed to help relieve these symptoms. With this angioplasty/stent procedure, patients are placed on the drug clopidogrel to help prevent clots from forming and narrowing of the blood vessels. Clopidogrel is a blood thinner that prevents clots from forming similar to an aspirin, but is more powerful and effective. Markers, or substances, have been identified that cause worsening of the blockages in the blood vessels of the heart. Many of these substances have been shown to decrease with the use of clopidogrel. This occurs separately from clopidogrel's ability to prevent clots. Endothelial progenitor cells, or EPCs, come mostly from the bone marrow and is helpful in repairing damage to the lining of the blood vessels of the heart. The EPCs help balance out the damage incurred in the blood vessels from those harmful markers. Several other drugs commonly used in heart disease have recently been shown to improve EPCs function. With this in mind, it is important to understand more of clopidogrel's function. A decrease in markers that cause worsening of the blockages, and an increase in the number of cells that will help repair damaged blood vessels of the heart is important in avoiding future chest pain and heart attacks. This may be how clopidogrel is currently protecting patients from developing new blockages. The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 80 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or females without child bearing potential aged 21-80 years
- •Known coronary artery disease by angiogram or documented myocardial infarction.
- •Able to provide written informed consent
排除标准
- •Treated with clopidogrel or ticlodipine in the previous 3 months
- •Age < 21 or >80 years
- •Premenopausal females with potential for pregnancy
- •Allergy to clopidogrel or aspirin
- •Initiation or change in dose of any concomitant medical therapy within 2 months before the study
- •Uncontrolled hypertension with BP>180 mmHg systolic and >120 mmHg diastolic
- •Treated with coumadin therapy
- •Intolerance or allergy to statins
- •Acute infection in previous 4 weeks
- •History of substance abuse
- •Uninterpretable PAT test
- •Current neoplasm
- •Chronic renal failure [creatinine > 2.5 mg/dL] or liver failure (Liver enzymes >2X normal)
- •Acute coronary syndrome, heart failure, CVA, coronary intervention within 3 months
- •Known aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure.
- •Inability to give informed consent
- •Inability to return to Emory for follow-up
研究组 & 干预措施
Clopidogrel/Placebo
Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks.
干预措施: Clopidogrel (Drug)
Clopidogrel/Placebo
Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks.
干预措施: Placebo (Drug)
Placebo/Clopidogrel
Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks.
干预措施: Clopidogrel (Drug)
Placebo/Clopidogrel
Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Nitroglycerin-mediated Vasodilation
时间窗: Baseline, Week 12
Nitroglycerin (NTG)-mediated vasodilation was measured after 0.4 mg of NTG was administered sublingually. Brachial artery images were obtained via ultrasound after three minutes of NTG administration. Measurements from the twelve frames will be averaged to calculate the percent change in diameter of the brachial artery from baseline to 12 weeks.
Endothelial Progenitor Cells (EPCs)
时间窗: Week 12
The circulating progenitor-enriched population of cells was measured by the expression of surface antigens using direct flow cytometry for CD34+, CD34+/CD133+, CD34+/ VEGF2R+ and CD34+/CD133+/VEGF2R+
Flow-mediated Dilation (FMD)
时间窗: Baseline, Week 12
Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks.
次要结局
- Oxidative Stress Markers(Week 12)
- Pulse Wave Velocity (PWV)(Week 12)
- Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP)(Week 12)
- Inflammatory Marker CD40 Ligand(Week 12)
研究者
Arshed A. Quyyumi
Professor of Medicine
Emory University
