Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells Mediated Through Multiple Mechanisms in Patients With High Risk for Cardiovascular Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Circulating EPCs Number
研究概览
简要总结
- The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases.
- This double-blind, randomized, placebo-controlled trial to evaluate the effects of cilostazol on human early EPCs and endothelial function as well as the potential mechanisms of action in patients with high risk for cardiovascular disease.
详细描述
-
titration of drugs
-
run-in period: eligible subjects are screened and baseline blood samples are obtained
-
study period: 12 weeks
- subjects with cilostazol and subjects with dummy placebo
- On the first day after the end of the study period, the follow-up data are obtained by the same procedure
- blood sampling and measurement of serum biomarkers
- obtained from peripheral veins in all study subjects at the run-in period and the end of the treatment period of the study
- sent for isolation, cell culture, and assays of human EPCs
- also stored for enzyme-linked immunosorbent assay (stromal cell derived factor-alfa1, adiponectin, soluble thrombomodulin, vascular endothelial growth factor)
-
assays of human EPCs
-
colony formation by EPCs
-
quantification of EPCs and apoptotic endothelial cells
-
chemotactic motility, proliferation/viability and apoptosis assays
-
measurement of flow-mediated dilatation (FMD) of left brachial artery by sonography
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •high-risk patients who have at least one of the following situations without pre-existing cardiovascular disease including peripheral artery disease or coronary artery disease:
- •type 2 diabetes mellitus
- •metabolic syndrome
- •stage 3 (or more advanced) chronic kidney disease
- •2 or more coronary risk factors (male > 45 years or female > 55 years, hypertension, tobacco smoking, hyperlipidemia, family history of cardiovascular disease)
排除标准
- •ankle-brachial index less than 0.9 or more than 1.3 in one or both legs
- •significant stenosis (more than 50% as compared to reference vessel) in peripheral artery on image study
- •symptoms suggesting peripheral artery disease in at least one leg
- •clinical or electrocardiographic evidence of coronary artery disease
- •clinical evidence of cerebrovascular disease
- •severe liver dysfunction (transaminases >10 times of upper normal limit, history of liver cirrhosis, or hepatoma)
- •left ventricular ejection fraction (<50% by echocardiography)
- •documented active malignancy
- •chronic inflammatory disease
- •known drug allergy history for cilostazol
- •current use of cilostazol or any other cAMP-elevator
- •premenopausal women
研究组 & 干预措施
Cilostazol
One tablet (100 mg) twice per day for 12 weeks
干预措施: Cilostazol (Drug)
Dummy Placebo
One tablet twice per day for 12 weeks
干预措施: Dummy Placebo (Drug)
结局指标
主要结局
Circulating EPCs Number
时间窗: 3 months
Peripheral blood mononuclear cells (one million cells in each) are suspended in 100 µL phosphate-buffered saline and incubated for 30 min with monoclonal antibodies against human peridinin chlorophyll protein-conjugated cluster of differentiation antigen-45, phycoerythrin-conjugated anti-human cluster of differentiation antigen-34 antibody and anti-human kinase insert domain receptor (KDR) antibody conjugated with Alexa Flour 647. Cells are washed and analyzed on a FACSCalibur flow cytometer with 100,000 events in the lymphocyte gate. EPCs, which are defined as negative for cluster of differentiation antigen-45 and positive for cluster of differentiation antigen-34 and KDR. Based on the peripheral blood mononuclear cell counts, the absolute number of circulating EPCs/µL is calculated.
次要结局
- Viability (Proliferation) of EPCs(3 months)