- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01952756
Effect of Cilostazol Endothelial Progenitor Cells and Collateral Formation in Peripheral Occlusive Artery Disease (PAOD)
July 16, 2014 updated by: National Cheng-Kung University Hospital
Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells and Collateral Formation Assessed by Dual-energy 128-row CT Angiography Mediated Through Multiple Mechanisms in Patients With Mild-to-moderate PAOD
- The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as PAOD.
- 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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
titration of drugs
- run-in period: eligible subjects are screened and baseline blood samples are obtained
study period: 12 weeks
- 24 subjects with cilostazol and 20 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
- collateral vessels formation and distal run-off assessed by dual-energy multi-slice computed tomography angiography
- echocardiographic examinations to evaluate left ventricular functions
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Tainan, Taiwan, 704
- National Cheng Kung University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- ankle-brachial index (ABI) less than 0.9 in one or both legs but no obvious symptoms of intermittent claudication
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Cilostazol
One tablet (100 mg) twice per day for 12 weeks
|
One tablet (100 mg) twice per day for 12 weeks
Other Names:
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Placebo Comparator: Dummy Placebo
One tablet twice per day for 12 weeks
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One tablet twice per day for 12 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Circulating EPCs Number
Time Frame: 3 months
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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.
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Colony Formation by EPCs
Time Frame: 3 months
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Peripheral blood mononuclear cells are isolated by density gradient centrifugation according to standard protocols.
After centrifugation, cells are washed, resuspended in M199 medium supplemented with 20% (vol/vol) fetal bovine serum, 10 ng/ml vascular endothelial growth factor, 2 ng/ml basic-fibroblast growth factor, 10 ng/ml epidermal growth factor and 2 ng/ml insulin growth factor, and cultured in 24-well plates coated with human fibronectin for 7 days.
EPCs cells are confirmed by uptake of acetyl-low density lipoprotein and lectin and by the expression of EPC markers.
Cells are harvested after 7 days, fixed and stained with crystal violet reagent.
The colony densities are quantified with an Olympus microscope at 100-fold magnification using an imaging measurement software.
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3 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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3 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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. Erratum In: J Am Heart Assoc. 2016;5(7). pii: e002090. doi: 10.1161/JAHA.116.002090.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2012
Primary Completion (Actual)
September 1, 2013
Study Completion (Actual)
September 1, 2013
Study Registration Dates
First Submitted
September 21, 2013
First Submitted That Met QC Criteria
September 25, 2013
First Posted (Estimate)
September 30, 2013
Study Record Updates
Last Update Posted (Estimate)
July 18, 2014
Last Update Submitted That Met QC Criteria
July 16, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Atherosclerosis
- Peripheral Arterial Disease
- Peripheral Vascular Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Neuroprotective Agents
- Protective Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Phosphodiesterase Inhibitors
- Phosphodiesterase 3 Inhibitors
- Cilostazol
Other Study ID Numbers
- NCKUH-10103043/BR-100-134
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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