Effect of Cilostazol on Endothelial Progenitor Cells and Endothelial Function in High Risk for Cardiovascular Disease

National Cheng-Kung University

Status and phase: Completed; Phase 4

Conditions: Cardiovascular Diseases

Treatments: Drug: Cilostazol; Drug: Dummy Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02194686

B-BR-101-121

NCKUH-10203022 (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.
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 high risk for cardiovascular disease.

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

Enrollment: 71 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: 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)

Exclusion Criteria:

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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71 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