Ignite Creation Date:
2025-12-24 @ 11:25 PM
Ignite Modification Date:
2026-03-27 @ 11:43 AM
Study NCT ID:
NCT01952756
Status:
COMPLETED
Last Update Posted:
2014-07-18
First Post:
2013-09-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Cilostazol Endothelial Progenitor Cells and Collateral Formation in Peripheral Occlusive Artery Disease (PAOD)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058729', 'term': 'Peripheral Arterial Disease'}], 'ancestors': [{'id': 'D050197', 'term': 'Atherosclerosis'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D016491', 'term': 'Peripheral Vascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077407', 'term': 'Cilostazol'}], 'ancestors': [{'id': 'D013777', 'term': 'Tetrazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011804', 'term': 'Quinolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 44}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-07', 'completionDateStruct': {'date': '2013-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-07-16', 'studyFirstSubmitDate': '2013-09-21', 'studyFirstSubmitQcDate': '2013-09-25', 'lastUpdatePostDateStruct': {'date': '2014-07-18', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-09-30', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Viability (Proliferation) of EPCs', 'timeFrame': '3 months', 'description': '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.'}], 'primaryOutcomes': [{'measure': 'Circulating EPCs Number', 'timeFrame': '3 months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Colony Formation by EPCs', 'timeFrame': '3 months', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['cilostazol', 'endothelial progenitor cells', 'vasculogenesis', 'angiogenesis', 'peripheral arterial disease', 'biomarkers'], 'conditions': ['Peripheral Arterial Diseases']}, 'referencesModule': {'references': [{'pmid': '22339730', 'type': 'BACKGROUND', 'citation': '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': '22473072', 'type': 'BACKGROUND', 'citation': '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': '27207972', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '1. The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as PAOD.\n2. 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.', 'detailedDescription': '1. titration of drugs\n\n 1. run-in period: eligible subjects are screened and baseline blood samples are obtained\n 2. study period: 12 weeks\n\n * 24 subjects with cilostazol and 20 subjects with dummy placebo\n * On the first day after the end of the study period, the follow-up data are obtained by the same procedure\n 3. blood sampling and measurement of serum biomarkers\n\n * obtained from peripheral veins in all study subjects at the run-in period and the end of the treatment period of the study\n * sent for isolation, cell culture, and assays of human EPCs\n * also stored for enzyme-linked immunosorbent assay (Stromal cell derived factor-alfa1, adiponectin, soluble thrombomodulin, vascular endothelial growth factor)\n2. assays of human EPCs\n\n 1. colony formation by EPCs\n 2. quantification of EPCs and apoptotic endothelial cells\n 3. chemotactic motility, proliferation/viability and apoptosis assays\n3. collateral vessels formation and distal run-off assessed by dual-energy multi-slice computed tomography angiography\n4. echocardiographic examinations to evaluate left ventricular functions'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ankle-brachial index (ABI) less than 0.9 in one or both legs but no obvious symptoms of intermittent claudication\n\nExclusion Criteria:\n\n* obvious symptoms of intermittent claudication\n* severe PAD (Fontaine grading \\> 3) or critical limb ischemia in at least one leg\n* severe liver dysfunction (transaminases \\>10 times of upper normal limit, history of liver cirrhosis, or hepatoma)\n* \\> stage 4 chronic kidney disease (end-stage renal disease with chronic dialysis not excluded)\n* left ventricular ejection fraction \\<50% by echocardiography\n* documented active malignancy\n* chronic inflammatory disease\n* planned coronary intervention or endovascular therapy or bypass surgery within 3 months\n* known drug allergy history for cilostazol\n* current use of cilostazol or any other cAMP-elevator\n* premenopausal women'}, 'identificationModule': {'nctId': 'NCT01952756', 'briefTitle': 'Effect of Cilostazol Endothelial Progenitor Cells and Collateral Formation in Peripheral Occlusive Artery Disease (PAOD)', 'organization': {'class': 'OTHER', 'fullName': 'National Cheng-Kung University Hospital'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'NCKUH-10103043/BR-100-134'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Cilostazol', 'description': 'One tablet (100 mg) twice per day for 12 weeks', 'interventionNames': ['Drug: Cilostazol']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Dummy Placebo', 'description': 'One tablet twice per day for 12 weeks', 'interventionNames': ['Drug: Dummy Placebo']}], 'interventions': [{'name': 'Cilostazol', 'type': 'DRUG', 'otherNames': ['Pletaal (brand name)'], 'description': 'One tablet (100 mg) twice per day for 12 weeks', 'armGroupLabels': ['Cilostazol']}, {'name': 'Dummy Placebo', 'type': 'DRUG', 'otherNames': ['Placebo', 'Control'], 'description': 'One tablet twice per day for 12 weeks', 'armGroupLabels': ['Dummy Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '704', 'city': 'Tainan', 'country': 'Taiwan', 'facility': 'National Cheng Kung University Hospital', 'geoPoint': {'lat': 22.99083, 'lon': 120.21333}}], 'overallOfficials': [{'name': 'Ting-Hsing Chao, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Cheng-Kung University Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cheng-Kung University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Department of Health, Executive Yuan, R.O.C. (Taiwan)', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'SPONSOR'}}}}