Autologous Bone Marrow Stem Cell Transfer in Patients With Chronical Critical Limb Ischemia and Diabetic Foot
A total of 90 patients suffering from end stage-IV Fontaine /CLI and diabetic foot with an ulcerated limb in whom all previous therapeutic strategies failed (e.g. surgical revascularization) will be selected and undergo local transplantation of ABMSCs. The efficacy/safety of this therapy will be assessed by using several endpoints such as (a) prevention of amputation, (b) wound healing and (c) degree of angiogenesis. In order to assess the limb ischemia and hypoxia the several tests and measurements will be performed pre- and post transplantation at a variety of time intervals. The measurements include: TP-toe pressure measurements (by Periflux 5000 Laser Doppler and Oxymetry system), SPP-skin perfusion pressure, ABI-ankle brachial index, LDP-laser Doppler baseline and heat perfusion assessment, TcpO2 without and with O2 provocation inhalation test. In addition, a battery of biochemical and hematological tests of peripheral venous blood sample will be performed.The quality form "EQ-50" will be completed.
8.1 Primary objective: To evaluate an efficacy-safety profile of autologous bone marrow stem cells (ABMSCs) transplantated into chronically and critically ischemic limb (CLI) and into diabetic foot in stage IV Fontaine, Rutherfod 4-6 classification.
8.2 Secondary objectives: 8.2.1 To assess effect of ABMSCs on tissue perfusion of ischemic limb after transplantation by transcutaneous oximetry and the laser Doppler flowmetry using Periflux 5000 system under normal and provocation test conditions. In addition, wound healing of ulcers will be evaluated using a planimetry method from photographs of affected skin taken pre- and post-transplantation.
8.2.2 Relationship between CD 34 progenitor counts separated on gradient-density separation centrifuge from Harvest Technologies and overall effectiveness and safety to treat ischemic limb.
8.3 Priorities: Beside assessment of effectiveness and safety of ABMSCs transplantation ultimate emphasis will be put on avoiding limb amputation. This has significant socioeconomic impact. Therefore this project belongs to the priority programs of clinical research in cardiovascular diseases.
|Critical Limb Ischemia||Procedure: BMAC application in Critical Limb Ischemia||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Autologous Bone Marrow Stem Cell Transfer in Patients With Chronical Critical Limb Ischemia and Diabetic Foot|
- Major limb amputation [ Time Frame: 120 days ]The measure is the number of major limb amputations within 120 days from the procedure.
- Tissue perfusion measurements [ Time Frame: 120 days ]Measurements of circulatory and blood parameters by laser Doppler flowmetry (TCPO2, TCPCO2, ankle-brachial index - ABI, toe-pressure-TP, toe-brachial index-TBI, skin-persusion pressure-SPP. Peripheral blood tests - white blood cell counts, differention counts, fibrinogen CRP and platelet counts. Bone marrow concentrate analysis to assess the number of CD34 progenitor cells, PQ-50 quality of life questionnaire. Follow-up angiogrwaphy at 120 postoperative days, wound healing measurements.
|Study Start Date:||October 2008|
|Study Completion Date:||December 2010|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Experimental: BMAC treatment active group
Collection of 240ml from both illiac crests, followed by gradient density centrifugation, resulting in obtaining 40ml of BMAC. This ammount is applied by one ml per injection into the critical limb ischemia along the calf vessels.
Procedure: BMAC application in Critical Limb Ischemia
Collection of 240ml from both illiac crests, followed by gradient density centrifugation, resulting in obtaining 40ml of BMAC (Bone-Marrow Aspiration Concentrate). BMAC is subsequently administered into the ischemic limb along calf vessels.
No Intervention: Control Study Group
Standard treatment group of patients with CLI after surgical or interventional revascularisation will serve as control.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01232673
|Principal Investigator:||Vaclav Prochazka, MD, PhD||University Hospital Ostrava|