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OpenTrials
Completed

NCT Number: NCT02194686

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

1. The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases. 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.

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Key information

Conditions

Cardiovascular Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

About this study

  • titration of drugs
  • run-in period: eligible subjects are screened and baseline blood samples are obtained
  • 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
  • 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)
  • assays of human EPCs
  • colony formation by EPCs
  • quantification of EPCs and apoptotic endothelial cells
  • chemotactic motility, proliferation/viability and apoptosis assays
  • measurement of flow-mediated dilatation (FMD) of left brachial artery by sonography

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

high-risk patients who have at least one of the following situations without pre-existing cardiovascular disease including peripheral artery disease or coronary artery disease:

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

Exclusion criteria

  • 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

Treatment and study plan

Cilostazol

Drug

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

Other names: Pletaal (brand name)

Dummy Placebo

Drug

One tablet twice per day for 12 weeks

Other names: Placebo, Control

Primary outcomes

  1. Circulating EPCs Number

    Time frame: 3 months

    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.

Secondary outcomes

  1. Viability (Proliferation) of EPCs

    Time frame: 3 months

    250,000 cells are seeded in each well of a 96-well plate and the cells are added with 200 μl of the culture medium and incubated at 37°C. Medium change is performed 3 days later. On 7th day, the plate is then re-incubated with 100 μl fresh medium and additional 50 μl of 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2 Hydrogen-Tetrazolium-5-Carboxanilide reagent, and further incubated in dark at 37°C for 4 h. After incubation, the orange colored complex formed is read at 450 nm using a microplate reader with a 450 nm reference filter.

Other outcomes

  1. FMD of the Brachial Artery

    Time frame: 3 months

    FMD in response to reactive hyperemia is measured in the left brachial artery in a quiet, temperature-controlled room after 10 min of bed rest. A high-resolution ultrasound machine equipped with a 7.5 mega Hertz linear array probe is used for the study. Arterial diameters are measured at the baseline and during reactive hyperemia. FMD is calculated as the percentage change in diameter compared with the baseline.

Sponsors and collaborators

Lead sponsor

National Cheng-Kung University Hospital

Other

Collaborators

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

Registry information

Official study title

Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells Mediated Through Multiple Mechanisms in Patients With High Risk for Cardiovascular Disease

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Jul 18, 2014
Registry last updated
Oct 14, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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