Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells and Endothelial Function Mediated Through Modification of Vasculogenesis and Angiogenesis Factors in Patients With Stable Coronary Artery Disease
Trial Snapshot
- Phase
- Phase 4
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Circulating EPCs Number
Study Overview
Brief Summary
- The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as coronary artery disease (CAD) and cardiovascular high risk.
- 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 CAD and cardiovascular high risk.
Detailed Description
-
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)
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assays of human EPCs
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colony formation by EPCs
-
quantification of EPCs and apoptotic endothelial cells
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chemotactic motility, proliferation/viability and apoptosis assays
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measurement of flow-mediated dilatation (FMD) of left brachial artery by sonography
-
assessment of long-term cardiovascular outcomes
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •stable CAD documented by stress test, computed tomography angiography or coronary angiography or
- •old myocardial infarction (>6 months)
- •history and evidence of CAD
- •history and evidence of cerebrovascular accident
- •history and evidence of peripheral artery disease
- •diabetes mellitus
- •metabolic syndrome
- •stage 3 to 5 chronic kidney disease
- •at least 2 of the followings: male ≥45 years old or female ≥55 years old; hypertension; current or past 3-year tobacco smoking; hyperlipidemia; family history of premature CAD (male <55 years old or female <65 years old)
Exclusion Criteria
- •unstable CAD
- •have plan to do percutaneous intervention or bypass surgery for CAD or peripheral artery disease within recent 3 months
- •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
Arms & Interventions
Cilostazol
One tablet (100 mg) twice per day for 12 weeks
Intervention: Cilostazol (Drug)
Dummy Placebo
One tablet twice per day for 12 weeks
Intervention: Dummy Placebo (Drug)
Outcomes
Primary Outcomes
Circulating EPCs Number
Time Frame: 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.
Secondary Outcomes
- Composite Major Adverse Cardiovascular Events (MACE)(at least 1 year)
- Viability (Proliferation) of EPCs(3 months)
- composite major coronary events(at least 1 year)