Ignite Creation Date:
2025-12-24 @ 9:09 PM
Ignite Modification Date:
2026-01-02 @ 2:39 AM
Study NCT ID:
NCT04255004
Status:
COMPLETED
Last Update Posted:
2020-02-05
First Post:
2020-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Autologous Peripheral Blood Mononuclear Cells in Diabetic Foot Patients With No-option Critical Limb Ischemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000089802', 'term': 'Chronic Limb-Threatening Ischemia'}, {'id': 'D017719', 'term': 'Diabetic Foot'}], 'ancestors': [{'id': 'D058729', 'term': 'Peripheral Arterial Disease'}, {'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'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D007511', 'term': 'Ischemia'}, {'id': 'D003925', 'term': 'Diabetic Angiopathies'}, {'id': 'D016523', 'term': 'Foot Ulcer'}, {'id': 'D007871', 'term': 'Leg Ulcer'}, {'id': 'D012883', 'term': 'Skin Ulcer'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D048909', 'term': 'Diabetes Complications'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D003929', 'term': 'Diabetic Neuropathies'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'We would enroll a cohort of 38 consecutive diabetic patients with CLI in charge at the Diabetic Foot Unit of the San Donato Hospital in Arezzo or referred from other Italian hospitals, who have no option for revascularization or are not further eligible for revascularization according to ESVS ESC 2017 criteria to undergo PB-MNC implantation. Furthermore, an historical control group, with a 1:1 case-control ratio, will be collected backwards from our records, when PBMNCs cellular therapy was not available in our center, with same no-option CLI diagnosis.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 76}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-01', 'completionDateStruct': {'date': '2019-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-01-31', 'studyFirstSubmitDate': '2020-01-25', 'studyFirstSubmitQcDate': '2020-01-31', 'lastUpdatePostDateStruct': {'date': '2020-02-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Amputation-free survival at 1 month', 'timeFrame': '1 month', 'description': 'rate of non amputated limb 1 month after the intervention'}, {'measure': 'Amputation-free survival at 3 months', 'timeFrame': '3 months', 'description': 'rate of non amputated limb 3 months after the intervention'}, {'measure': 'Amputation-free survival at 6 months', 'timeFrame': '6 months', 'description': 'rate of non amputated limb 6 months after the intervention'}, {'measure': 'Amputation-free survival at 12 months', 'timeFrame': '12 months', 'description': 'rate of non amputated limb 12 months after the intervention'}, {'measure': 'Amputation-free survival at 18 months', 'timeFrame': '18 months', 'description': 'rate of non amputated limb 18 months after the intervention'}, {'measure': 'Amputation-free survival at 24 months', 'timeFrame': '24 months', 'description': 'rate of non amputated limb 24 months after the intervention'}, {'measure': 'risk of death at 1 month', 'timeFrame': '1 month', 'description': 'rate of dead subjects 1 month after the intervention'}, {'measure': 'risk of death at 3 months', 'timeFrame': '3 months', 'description': 'rate of dead subjects 3 months after the intervention'}, {'measure': 'risk of death at 6 months', 'timeFrame': '6 months', 'description': 'rate of dead subjects 6 months after the intervention'}, {'measure': 'risk of death at 12 months', 'timeFrame': '12 months', 'description': 'rate of dead subjects 12 months after the intervention'}, {'measure': 'risk of death at 18 months', 'timeFrame': '18 months', 'description': 'rate of dead subjects 18 months after the intervention'}, {'measure': 'risk of death at 24 months', 'timeFrame': '24 months', 'description': 'rate of dead subjects 24 months after the intervention'}, {'measure': 'probability of healing at 1 month', 'timeFrame': '1 month', 'description': 'rate of healed subjects 1 month after the intervention'}, {'measure': 'probability of healing at 3 months', 'timeFrame': '3 months', 'description': 'rate of healed subjects 3 months after the intervention'}, {'measure': 'probability of healing at 6 months', 'timeFrame': '6 months', 'description': 'rate of healed subjects 6 months after the intervention'}, {'measure': 'probability of healing at 12 months', 'timeFrame': '12 months', 'description': 'rate of healed subjects 12 months after the intervention'}, {'measure': 'probability of healing at 18 months', 'timeFrame': '18 months', 'description': 'rate of healed subjects 18 months after the intervention'}, {'measure': 'probability of healing at 24 months', 'timeFrame': '24 months', 'description': 'rate of healed subjects 24 months after the intervention'}], 'secondaryOutcomes': [{'measure': 'transcutaneous oxygen measurement (TcPO2) variation', 'timeFrame': '0-3 months', 'description': 'comparison of TcPO2 at the second follow up (3 months after intervention) with the baseline measure'}, {'measure': 'Healing time', 'timeFrame': 'within 24 months', 'description': 'time to reach complete epithelialization'}, {'measure': 'rest pain', 'timeFrame': '0-1-3 months', 'description': 'comparison of rest pain measured by a numeric rating scale (NRS) min 0 - max 10, where 10 is the worst pain the patient has felt'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['autologous peripheral blood mononuclear cell, diabetic foot'], 'conditions': ['Critical Limb Ischemia', 'Diabetic Foot']}, 'referencesModule': {'references': [{'pmid': '26391460', 'type': 'BACKGROUND', 'citation': 'Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, Conte MS, Murad MH. 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Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005 Sep;28(9):2155-60. doi: 10.2337/diacare.28.9.2155.'}, {'pmid': '23111057', 'type': 'BACKGROUND', 'citation': 'Fadini GP, Albiero M, Vigili de Kreutzenberg S, Boscaro E, Cappellari R, Marescotti M, Poncina N, Agostini C, Avogaro A. Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes Care. 2013 Apr;36(4):943-9. doi: 10.2337/dc12-1084. Epub 2012 Oct 30.'}, {'pmid': '30172703', 'type': 'BACKGROUND', 'citation': 'Dong Z, Pan T, Fang Y, Wei Z, Gu S, Fang G, Liu Y, Luo Y, Liu H, Zhang T, Hu M, Guo D, Xu X, Chen B, Jiang J, Yang J, Shi Z, Zhu T, Shi Y, Liu P, Fu W. Purified CD34+ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-Month results of a prospective randomised single-blinded non-inferiority trial. EBioMedicine. 2018 Sep;35:46-57. doi: 10.1016/j.ebiom.2018.08.038. Epub 2018 Aug 29.'}, {'pmid': '23915883', 'type': 'RESULT', 'citation': 'Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. doi: 10.1016/S0140-6736(13)61249-0. Epub 2013 Aug 1.'}, {'pmid': '25650396', 'type': 'RESULT', 'citation': 'Reinecke H, Unrath M, Freisinger E, Bunzemeier H, Meyborg M, Luders F, Gebauer K, Roeder N, Berger K, Malyar NM. Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence. Eur Heart J. 2015 Apr 14;36(15):932-8. doi: 10.1093/eurheartj/ehv006. Epub 2015 Feb 2.'}, {'pmid': '29430981', 'type': 'RESULT', 'citation': 'Vas PRJ, Edmonds M, Kavarthapu V, Rashid H, Ahluwalia R, Pankhurst C, Papanas N. The Diabetic Foot Attack: "\'Tis Too Late to Retreat!". Int J Low Extrem Wounds. 2018 Mar;17(1):7-13. doi: 10.1177/1534734618755582. Epub 2018 Feb 12.'}]}, 'descriptionModule': {'briefSummary': 'The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing.', 'detailedDescription': "This is an interventional study with historical control group carried out to assess as primary outcome major amputations, overall mortality, number of healed patients in group of patients who received repetitive intra-muscular implant of PBMNCs (3 times; 4-week interval) in comparison to a historical internal control group with a 1:1 case-control ratio. Secondary outcomes are TCPO2, healing time and rest pain.\n\nNo-option critical limb ischaemia is defined by evidence of no run-off pedal vessels, failure after several percutaneous intervention and no longer possible re-intervention, failure after infra-genicular bypass grafting, no-walking capacity with severe comorbidities unfit for surgical or endovascular procedures.\n\nInclusion criteria are: a) ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \\<30 mmHg; b) ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System c) not eligible for angioplasty or vascular surgery or following failed revascularization; d) possibility to save foot support.\n\nExclusion criteria are: a) lesion site above the tibial-tarsal joint; b) moderate or severe infection according by the WiFI classification system; c) NYHA class IV; d) Anemia (Hb\\<8g/dl); e) coagulation disorder/thrombocytopenia (PLT\\< 50,000 per microliter); f) active cancer/leukemia or lymphoma hematological disease.\n\nStandard of care in both groups includes: diabetes control maximization by the diabetologist, comprehensive foot assessment by the nurse together with the diabetologist, including determination of vibration perception threshold, 10-g monofilament test and TcpO2 measurement, dressings, off-loading and systemic therapy according to the IWGDF guidelines .\n\nInformed consent for participation in the study during the progress of the clinical trial is obtained from all subjects.\n\nConcentration of PB-MNCs autologous cell therapy is produced by a filtration-based point-of-care device with the intended for use intra-operatively, from 120 mL of anticoagulated blood. All the procedures are performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) is collected through a peripheral venous access, than loaded and gravity filtration is allowed in about 10 minutes. During filtration, MNCs are captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) are not retained. After appropriate surgical debridement of the wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses) are injected along the relevant axis below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.\n\nFoot-sparing surgery, the removal of all the unviable tissue and the reconstruction of the foot to allow a functional deambulation,is performed at the same time of the last implant in the patients with increased TcpO2 value above 30 mmHg. Between the implants, diabetologists together with nurses evaluated changing in pain, infection signs, wound size, demarcation of the necrosis, granulation tissue formation, perilesional tissue trophism and TcpO2 value to optimize standard of care. After the first treatment, a two years follow-up is registered, with evaluation at 1-3-6-12-18-24 months.\n\nA baseline assessment is carried out, in order to estimate any differences among cases and controls before the treatment. Statistical evaluation includes non-parametric tests (Mann-Whitney U test for independent samples for continuous variables and Cochrane chi-square test for discrete variables), evaluation of Relative Risk (RR), Absolute Risk Reduction (ARR), Relative Risk Reduction (RRR) and Number Needed to Treat (NNT), multivariate survival analysis (Kaplan-Meier's survival analysis model)."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \\<30 mmHg;\n* ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System\n* not eligible for angioplasty or vascular surgery or following failed revascularization;\n* possibility to save foot support.\n\nExclusion Criteria:\n\n* lesion site above the tibial-tarsal joint;\n* moderate or severe infection according by the WiFI classification system;\n* NYHA class IV; d) Anemia (Hb\\<8g/dl);\n* coagulation disorder/thrombocytopenia (PLT\\< 50,000 per microliter);\n* active cancer/leukemia or lymphoma hematological disease.'}, 'identificationModule': {'nctId': 'NCT04255004', 'briefTitle': 'Autologous Peripheral Blood Mononuclear Cells in Diabetic Foot Patients With No-option Critical Limb Ischemia', 'organization': {'class': 'OTHER', 'fullName': 'Ospedale San Donato'}, 'officialTitle': 'Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients With No-option Critical Limb Ischemia', 'orgStudyIdInfo': {'id': 'MONODIAB-19-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'A-PBMNC therapy', 'description': 'Patients in A-PBMNC therapy are treated with wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses). This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.', 'interventionNames': ['Device: Pall Celeris System, point of care device for human cell therapy']}, {'type': 'NO_INTERVENTION', 'label': 'No A-PBMNC therapy', 'description': 'Patients in No A-PBMNC therapy receive only supportive treatment including wound care and pain killer drug.'}], 'interventions': [{'name': 'Pall Celeris System, point of care device for human cell therapy', 'type': 'DEVICE', 'description': 'Concentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.', 'armGroupLabels': ['A-PBMNC therapy']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Leonardo Ercolini, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Vascular Surgery Unit San Donato Hospital Arezzo'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'data should not be shared before study completion and approvation by all the collaborators. Sharing data before this time would jeopardize the integrity of the clinical trial process and risk the scientific validity of the results.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ospedale San Donato', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Alessia Scatena', 'investigatorAffiliation': 'Ospedale San Donato'}}}}