Bone Marrow Autograft in Limb Ischemia

Study Overview
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Brief Summary
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BALI (Bone marrow Autograft in Limb Ischemia) is a randomized double-blind trial comparing implantation of bone marrow - mononuclear cells versus placebo in patients presenting with critical leg ischemia and no surgical option. The main end point is the survival without major amputation 6 months after implantation. Biological studies are performed on bone marrow mononuclear cells (BM-MNC) to evaluate their angiogenic properties.

Detailed Description
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One hundred and ten patients with critical leg ischemia and no surgical option will be included. A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30 mL) for all included patients. For half of them, the BM-MNC are implanted on the same day whereas the others are implanted with a placebo cell-product (30 mL saline with 4 ml peripheral blood). For these patients the BM-MNC are cryo-conserved. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted. The main end point is the survival without major amputation 6 months after implantation. After this delay it is possible to use previously cryo-conserved BM-MNC. Likewise biological studies are performed on BM-MNC: flow-cytometry analysis of progenitor cells content, proteins and mRNAs expression, induced angiogenesis in animal models.

Official Title
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Cell Therapy in Critical Limb Ischemia

Conditions
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Peripheral Vascular Diseases

Intervention / Treatment
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* Procedure: Bone marrow harvest
* Procedure: Bone marrow harvest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critical limb ischemia No possible surgical treatment Exclusion Criteria: Ongoing infectious disease Gangrene extending beyond the digits Diabetes mellitus with HbA1c > 7.5% or with proliferative retinopathy History of malignant disease Contra-indication to general anaesthesia Chronic haemodialysis Prothrombin Time < 50% Recent onset (within 3 months) of myocardial infarction or brain infarction Contra-indication to modification of anti-platelet or anticoagulant therapy History of heparin-induced thrombocytopenia Unexplained haematological abnormality

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30mL). A placebo cell-product (30 mL saline with 4 ml peripheral blood) is implanted and the BM-MNC are cryo-conserved. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted. After 6 months, it is possible to use previously cryo-conserved BM-MNC. | Procedure: Bone marrow harvest<br>* Implantation of placebo<br>|
| Experimental: B<br>A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30mL) . The BM-MNC are implanted on the same day. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted | Procedure: Bone marrow harvest<br>* Implantation of bone marrow - mononuclear cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major amputation rate and mortality |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical symptoms and haemodynamical parameters |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Limb ischemia, Cell Therapy