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

NCT02174939 | Unknown Phase 4

• 2 other identifiers: A-BR-102-076NCKUH-10304022
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 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.

Conditions

Coronary Artery Disease

Keywords

cilostazol; progenitor cells; coronary artery disease; myocardial infarction; angiogenesis; biological markers; endothelial function

Outcome Measures

Primary Outcomes (1)

• Circulating EPCs Number

  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.

  3 months

Secondary Outcomes (3)

• Viability (Proliferation) of EPCs

  3 months

• Composite Major Adverse Cardiovascular Events (MACE)

  at least 1 year

• composite major coronary events

  at least 1 year

Other Outcomes (1)

• FMD of the Brachial Artery

  3 months

Study Arms (2)

Cilostazol

ACTIVE COMPARATOR

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

Drug: Cilostazol

Dummy Placebo

PLACEBO COMPARATOR

One tablet twice per day for 12 weeks

Drug: Dummy Placebo

Interventions

Cilostazol DRUG

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

Also known as: Pletaal (brand name)

Cilostazol

Dummy Placebo DRUG

One tablet twice per day for 12 weeks

Also known as: Placebo, Control

Dummy Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead
• Department of Health, Executive Yuan, R.O.C. (Taiwan): collaborator

Study Sites (1)

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Related Publications (3)

• 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.

  PMID: 22339730 BACKGROUND

• 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.

  PMID: 22473072 BACKGROUND

• 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.

  PMID: 24439864 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Infarction

Interventions

Cilostazol

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ting-Hsing Chao, MD

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ting-Hsing Chao, MD

CONTACT

886-6-2353535; chaoth@mail.ncku.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2014
• First Posted: June 26, 2014
• Study Start: February 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

TW (1)