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

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ClinicalTrials.gov Identifier: NCT02174939
Recruitment Status : Unknown
Verified October 2015 by National Cheng-Kung University Hospital.
Recruitment status was:  Recruiting
First Posted : June 26, 2014
Last Update Posted : October 14, 2015
Sponsor:
Collaborator:
Department of Health, Executive Yuan, R.O.C. (Taiwan)
Information provided by (Responsible Party):
National Cheng-Kung University Hospital

June 22, 2014
June 26, 2014
October 14, 2015
February 2014
October 2017   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT02174939 on ClinicalTrials.gov Archive Site
  • 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.
  • Composite Major Adverse Cardiovascular Events (MACE) [ Time Frame: at least 1 year ]
    This composite endpoint includes cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, congestive heart failure hospitalization, and target vessel revascularization.
  • composite major coronary events [ Time Frame: at least 1 year ]
    This composite endpoint includes fatal or nonfatal myocardial infarction, recurrent angina pectoris, and target vessel revascularization.
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.
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.
Same as current
 
Effect of Cilostazol on Endothelial Progenitor Cells and Endothelial Function in Coronary Artery Disease
Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells and Endothelial Function Mediated Through Modification of Vasculogenesis and Angiogenesis Factors in Patients With Stable Coronary Artery Disease
  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.
  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
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Coronary Artery Disease
  • Drug: Cilostazol
    One tablet (100 mg) twice per day for 12 weeks
    Other Name: Pletaal (brand name)
  • Drug: Dummy Placebo
    One tablet twice per day for 12 weeks
    Other Names:
    • Placebo
    • Control
  • Active Comparator: Cilostazol
    One tablet (100 mg) twice per day for 12 weeks
    Intervention: Drug: Cilostazol
  • Placebo Comparator: Dummy Placebo
    One tablet twice per day for 12 weeks
    Intervention: Drug: Dummy Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
300
60
December 2017
October 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
20 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
 
NCT02174939
A-BR-102-076
NCKUH-10304022 ( Other Grant/Funding Number: NCKUH )
No
Not Provided
Not Provided
National Cheng-Kung University Hospital
National Cheng-Kung University Hospital
Department of Health, Executive Yuan, R.O.C. (Taiwan)
Principal Investigator: Ting-Hsing Chao, MD National Cheng-Kung University Hospital
National Cheng-Kung University Hospital
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP