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

NCT01952756 | Completed Phase 4

• 1 other identifier: NCKUH-10103043/BR-100-134
• Study Type: interventional
• Target: 44
• 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 PAOD.
2. 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.

Conditions

Peripheral Arterial Diseases

Keywords

cilostazol; endothelial progenitor cells; vasculogenesis; angiogenesis; peripheral arterial disease; biomarkers

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)

• Colony Formation by EPCs

  3 months

Other Outcomes (1)

• Viability (Proliferation) of EPCs

  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:

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

You may not qualify if:

• 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

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 (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, 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

Peripheral Arterial Disease

Interventions

Cilostazol

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

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: September 21, 2013
• First Posted: September 30, 2013
• Study Start: January 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 18, 2014

Record last verified: 2014-07

Locations

TW (1)