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

NCT02194686 | Completed Phase 4

• 2 other identifiers: B-BR-101-121NCKUH-10203022
• Study Type: interventional
• Target: 71
• 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.
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 high risk for cardiovascular disease.

Conditions

Cardiovascular Diseases

Keywords

cilostazol; progenitor cells; cardiovascular disease; risk factors; 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 (1)

• Viability (Proliferation) of EPCs

  3 months

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:

• type 2 diabetes mellitus
• metabolic syndrome
• stage 3 (or more advanced) chronic kidney disease
• or more coronary risk factors (male \> 45 years or female \> 55 years, hypertension, tobacco smoking, hyperlipidemia, family history of cardiovascular disease)

You may not qualify if:

• 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

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

Location

Related Publications (4)

• 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

• Chao TH, Chen IC, Li YH, Lee PT, Tseng SY. Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells. J Am Heart Assoc. 2016 May 20;5(5):e003497. doi: 10.1161/JAHA.116.003497.

  PMID: 27207972 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Cilostazol

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

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: July 16, 2014
• First Posted: July 18, 2014
• Study Start: January 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

TW (1)