Effect of Cilostazol on Endothelial Progenitor Cells and Endothelial Function in Coronary Artery Disease

National Cheng-Kung University

Status and phase: Unknown; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Dummy Placebo; Drug: Cilostazol

Study type: Interventional

Funder types: Other

Identifiers

NCT02174939

A-BR-102-076

NCKUH-10304022 (Other Grant/Funding Number)

Details and patient eligibility

About

1. 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.
2. 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.

Full description

1. titration of drugs

   1. run-in period: eligible subjects are screened and baseline blood samples are obtained

   2. 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

   3. 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)

2. assays of human EPCs

   1. colony formation by EPCs
   2. quantification of EPCs and apoptotic endothelial cells
   3. chemotactic motility, proliferation/viability and apoptosis assays

3. measurement of flow-mediated dilatation (FMD) of left brachial artery by sonography

4. assessment of long-term cardiovascular outcomes

Enrollment: 300 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 2 patient groups, including a placebo group

Cilostazol

Active Comparator group

Description:

One tablet (100 mg) twice per day for 12 weeks

Treatment:

Drug: Cilostazol

Dummy Placebo

Placebo Comparator group

Description:

One tablet twice per day for 12 weeks

Treatment:

Drug: Dummy Placebo