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

NCT ID: NCT02174939

Last Updated: 2015-10-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2017-12-31

Brief Summary

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.

Detailed 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

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cilostazol

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

Group Type: ACTIVE_COMPARATOR

Cilostazol

Intervention Type: DRUG

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

Dummy Placebo

One tablet twice per day for 12 weeks

Group Type: PLACEBO_COMPARATOR

Dummy Placebo

Intervention Type: DRUG

One tablet twice per day for 12 weeks

Interventions

Cilostazol

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

Intervention Type: DRUG

Dummy Placebo

One tablet twice per day for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Pletaal (brand name); Placebo; Control

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Department of Health, Executive Yuan, R.O.C. (Taiwan)

OTHER_GOV

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ting-Hsing Chao, MD

Role: PRINCIPAL_INVESTIGATOR

National Cheng-Kung University Hospital

Locations

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ting-Hsing Chao, MD

Role: CONTACT

chaoth@mail.ncku.edu.tw

886-6-2353535 ext. 2382

Facility Contacts

Ting-Hsing Chao, MD

Role: primary

chaoth@mail.ncku.edu.tw

886-6-2353535 ext. 2382

References

Chao TH, Tseng SY, Li YH, Liu PY, Cho CL, Shi GY, Wu HL, Chen JH. A novel vasculo-angiogenic effect of cilostazol mediated by cross-talk between multiple signalling pathways including the ERK/p38 MAPK signalling transduction cascade. Clin Sci (Lond). 2012 Aug 1;123(3):147-59. doi: 10.1042/CS20110432.

Reference Type: BACKGROUND

PMID: 22339730 (View on PubMed)

Biscetti F, Pecorini G, Straface G, Arena V, Stigliano E, Rutella S, Locatelli F, Angelini F, Ghirlanda G, Flex A. Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism. Int J Cardiol. 2013 Aug 10;167(3):910-6. doi: 10.1016/j.ijcard.2012.03.103. Epub 2012 Apr 2.

Reference Type: BACKGROUND

PMID: 22473072 (View on PubMed)

Chao TH, Tseng SY, Chen IC, Tsai YS, Huang YY, Liu PY, Ou HY, Li YH, Wu HL, Cho CL, Tsai LM, Chen JH. Cilostazol enhances mobilization and proliferation of endothelial progenitor cells and collateral formation by modifying vasculo-angiogenic biomarkers in peripheral arterial disease. Int J Cardiol. 2014 Mar 15;172(2):e371-4. doi: 10.1016/j.ijcard.2013.12.295. Epub 2014 Jan 11. No abstract available.

Reference Type: BACKGROUND

PMID: 24439864 (View on PubMed)

Other Identifiers

NCKUH-10304022

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

A-BR-102-076

Identifier Type: -

Identifier Source: org_study_id