Effect of Cilostazol Endothelial Progenitor Cells and Collateral Formation in Peripheral Occlusive Artery Disease (PAOD)

National Cheng-Kung University

Status and phase: Completed; Phase 4

Conditions: Peripheral Arterial Diseases

Treatments: Drug: Dummy Placebo; Drug: Cilostazol

Study type: Interventional

Funder types: Other

Identifiers

NCT01952756

NCKUH-10103043/BR-100-134

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 PAOD.
2. This double-blind, randomized, placebo-controlled trial to evaluate the effects of cilostazol on human early EPCs and angiogenesis as well as the potential mechanisms of action in patients with mild-to-moderate PAOD.

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

      • 24 subjects with cilostazol and 20 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. collateral vessels formation and distal run-off assessed by dual-energy multi-slice computed tomography angiography

4. echocardiographic examinations to evaluate left ventricular functions

Enrollment: 44 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ankle-brachial index (ABI) less than 0.9 in one or both legs but no obvious symptoms of intermittent claudication

Exclusion criteria

• obvious symptoms of intermittent claudication
• severe PAD (Fontaine grading > 3) or critical limb ischemia in at least one leg
• severe liver dysfunction (transaminases >10 times of upper normal limit, history of liver cirrhosis, or hepatoma)
• > stage 4 chronic kidney disease (end-stage renal disease with chronic dialysis not excluded)
• left ventricular ejection fraction <50% by echocardiography
• documented active malignancy
• chronic inflammatory disease
• planned coronary intervention or endovascular therapy or bypass surgery within 3 months
• 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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44 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