Ignite Creation Date:
2025-12-24 @ 7:58 PM
Ignite Modification Date:
2026-01-03 @ 6:33 PM
Study NCT ID:
NCT00533104
Status:
COMPLETED
Last Update Posted:
2009-02-06
First Post:
2007-09-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cell Therapy in Chronic Limb Ischemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016491', 'term': 'Peripheral Vascular Diseases'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2004-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2009-02', 'completionDateStruct': {'date': '2009-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2009-02-05', 'studyFirstSubmitDate': '2007-09-19', 'studyFirstSubmitQcDate': '2007-09-19', 'lastUpdatePostDateStruct': {'date': '2009-02-06', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2007-09-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Survival without major amputation', 'timeFrame': '6 months after implantation'}], 'secondaryOutcomes': [{'measure': 'clinical symptoms and haemodynamic parameters', 'timeFrame': 'Within 6 months after implantation'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Limb ischemia', 'Cell Therapy'], 'conditions': ['Peripheral Vascular Diseases']}, 'referencesModule': {'references': [{'pmid': '17384655', 'type': 'RESULT', 'citation': 'Pignon B, Sevestre MA, Chatelain D, Albertini JN, Sevestre H. Histological changes after implantation of autologous bone marrow mononuclear cells for chronic critical limb ischemia. Bone Marrow Transplant. 2007 May;39(10):647-8. doi: 10.1038/sj.bmt.1705656. Epub 2007 Mar 26. No abstract available.'}, {'pmid': '31399109', 'type': 'DERIVED', 'citation': 'Al-Rifai R, Nguyen P, Bouland N, Terryn C, Kanagaratnam L, Poitevin G, Francois C, Boisson-Vidal C, Sevestre MA, Tournois C. In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia. J Transl Med. 2019 Aug 9;17(1):261. doi: 10.1186/s12967-019-2003-3.'}, {'pmid': '19207166', 'type': 'DERIVED', 'citation': 'Capiod JC, Tournois C, Vitry F, Sevestre MA, Daliphard S, Reix T, Nguyen P, Lefrere JJ, Pignon B. Characterization and comparison of bone marrow and peripheral blood mononuclear cells used for cellular therapy in critical leg ischaemia: towards a new cellular product. Vox Sang. 2009 Apr;96(3):256-65. doi: 10.1111/j.1423-0410.2008.01138.x. Epub 2008 Dec 15.'}]}, 'descriptionModule': {'briefSummary': 'The primary focus of the trial is safety and efficacy of the intra-muscular implantation of either bone-marrow, or peripheral blood mononuclear cells, in critical limb ischemia, as judged by the proportion of patients which are alive without major amputation 6 months after inclusion.', 'detailedDescription': 'Critical limb ischemia is a frequent situation whose incidence can be evaluated to 500 to 1,000 per million per year. Limb salvage is the main goal of therapy and is usually attempted by surgical or percutaneous vascularization procedures. However approximately 25 % of patients are not suitable for such procedures and it was estimated that less than half of these patients were alive without any major amputation after 6 months. In this setting cell therapy has been proposed to stimulate angiogenesis. The first significant experience in humans was reported by TATEISHI-YUYAMA et al who showed that autologous implantation of bone marrow mononuclear cells (BM-MNC) was safe and increased blood flow in ischemic limbs resulting in clinical improvement. The same authors did not observe any efficacy of peripheral blood mononuclear cells (PB-MNC). Subsequently other publications reported positive effects of PB-MNC which were harvested after previous treatment with haematopoietic growth factor to induce a mobilization of stem cells. However such a treatment could have deleterious effects in patients presenting with advanced arterial disease. In this context we propose a prospective bi-centric trial to evaluate the safety and efficacy of autologous implantation of either BM-MNC or PB-MNC without previous mobilization with hematopoïetic factor, in patients with critical limb ischemia.\n\nThe trial is designed in two steps : a first series of eight patients are treated with BM-MNC and the following eight will receive PB-MNC. An interim analysis is planned after these first sixteen cases. Based on this analysis, it will be decided to include 12 further patients with each type of cells.Patients are consecutively included as soon as they present with appropriate criteria and are not selected to receive one or another type of cells.\n\nBefore implantation, MNC counts, differential and viability are determined. CD34+, CD34+/CD133+ and CD34+/CD133+/flk-1+ cells are counted by flow-cytometry.\n\nClinical symptoms and TcPO2 are monitored 1, 2, 7 and 14 days, 1, 3, and 6 months after cell implantation. Blood cell count, C-reactive protein, Interleukin-6, tumor necrosis factor-α, myoglobin, and creatinin-kinase are determined at day 0, 1, 3 and 7 ; blood vascular-endothelial-growth-factor (VEGF) level and CD34+, CD34+/CD133+ blood cells are measured before and 72 hours after implantation'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with unilateral critical chronic limb ischemia but not suitable candidates for non-surgical or surgical revascularization\n* Before being included, the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, treponema pallidum\n\nExclusion Criteria:\n\n* Buerger disease\n* Ischemic ulcers with infectious symptoms\n* Diabetes mellitus with HbA1c \\> 7,5% or with proliferative retinopathy\n* Past or current malignancy\n* Contra-indication to general anaesthesia\n* Chronic haemodialysis\n* Prothrombin Time \\< 60%,\n* Recent onset (within 3 months) of myocardial infarction or brain infarction\n* Coronary angioplasty within 1 year\n* Atrial fibrillation, mechanical mitral prosthetic valve\n* Unexplained hematological abnormality.\n* Expected life span less than six months\n* Patient not competent to give informed consent'}, 'identificationModule': {'nctId': 'NCT00533104', 'briefTitle': 'Cell Therapy in Chronic Limb Ischemia', 'organization': {'class': 'OTHER', 'fullName': 'CHU de Reims'}, 'officialTitle': 'Critical Limb Ischemia Treatment by Local Intra-Muscular Injection of Autologous Mononuclear Cells', 'orgStudyIdInfo': {'id': 'PHRC Région 2003 / R11-05 / 95'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'BM-MNC', 'description': 'Patients are implanted with bone marrow - mononuclear cells', 'interventionNames': ['Procedure: BM-MNC preparation']}, {'type': 'EXPERIMENTAL', 'label': 'PB-MNC', 'description': 'Patients are implanted with peripheral blood - mononuclear cells', 'interventionNames': ['Procedure: PB-MNC preparation']}], 'interventions': [{'name': 'BM-MNC preparation', 'type': 'PROCEDURE', 'description': 'For autologous bone marrow - mononuclear cells preparation, 500ml of bone marrow are collected under general anaesthesia; mononuclear cells are separated using a blood-cells separator (COBE SPECTRA, GAMBRO BCT) and concentrated to produce a final volume of 40ml.\n\nCells are implanted 1 to 3 hours after preparation by multiple intramuscular injections into the gastrocnemius of the ischemic leg.(30 injection sites, 1 to 1.5 cm deep, spaced 1 cm apart,1 ml per injection).', 'armGroupLabels': ['BM-MNC']}, {'name': 'PB-MNC preparation', 'type': 'PROCEDURE', 'description': 'Peripheral blood - mononuclear cells are collected through cytapheresis with the same blood-cells separator which is adjusted to obtain a 40 mL cell product. No previous mobilization with hematopoïetic growth-factor is administered.\n\nCells are implanted 1 to 3 hours after preparation by multiple intramuscular injections into the gastrocnemius of the ischemic leg.(30 injection sites, 1 to 1.5 cm deep, spaced 1 cm apart,1 ml per injection).', 'armGroupLabels': ['PB-MNC']}]}, 'contactsLocationsModule': {'locations': [{'zip': '44000', 'city': 'Nantes', 'country': 'France', 'facility': 'Patricia LEMARCHAND', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}], 'overallOfficials': [{'name': 'Bernard PIGNON, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'University Hospital REIMS FRANCE'}, {'name': 'Marie-Antoinette SEVESTRE, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital AMIENS FRANCE'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'CHU de Reims', 'class': 'OTHER'}, 'responsibleParty': {'oldNameTitle': 'PIGNON / MD', 'oldOrganization': 'Centre Hospitalier Universitaire de REIMS - FRANCE'}}}}