Clinical trial NCT00377897: Cell Therapy With Bone Marrow Mononuclear Cells in Critical Leg Ischemia (CLI)
Official title: Optimisation d'un Produit de thérapie Cellulaire Autologue Par Cellules mononucléées médullaires Dans l'ischémie Critique Des Membres inférieurs liée à l'athérosclérose
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Critical Leg Ischemia
Keywords: critical leg ischemia
PAD
cell therapy
Lead sponsor: University of Paris 5 - Rene Descartes
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2006-09-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will treat by cell therapy 20 patients with critical leg ischemia (CLI) not eligible for revascularization or angioplasty. It will use exactly the same protocol as published by Tateishi-Yuyama et al. (Lancet 2002), using bone-marrow mononuclear cells (BMMNC).

Detailed description: Patients will be included with CLI according to the TASC criteria. Under general anesthesia, 500 ml of bone marrow is harvested in both iliac crests. After isolation and concentration of the BMMNC in 30 ml, 40 injections of around 0.75 ml will be done in the gastrocnemius of the ischemic leg, within 3 hours after preparation of the cell therapy product.

Patients will then be followed-up every week during one month and then every month during one year.

This study was approved by the ethical committee of Paris-Broussais HEGP (France) and our french regulatory agency (AFSSAPS).

It began including patients in January 2005 and will last until December 2007.

Eligibility criteria: Inclusion Criteria:

* Age \> 18
* Signature of informed consent
* Critical leg ischemia with ankle pressure \< 70 mmHg
* Ischemic ulcer or gangrene
* No possibility of surgical revascularization
* No possibility of angioplasty

Exclusion Criteria:

* Cancer
* Suspicion of a cancer on X-Ray, mammography or elevated PSA
* Age \< 18
* Life expectancy \< 6 months
* Active retinopathy
* Angioplasty or surgical revascularization within 3 months
* Stoke within 3 months
* HIV + or HCV/HBC+

Primary outcomes:
measure: Ankle brachial index
timeFrame: 6 months
measure: Healing
timeFrame: 1 year
measure: Amputation rate
timeFrame: 1 year
Secondary outcomes:
measure: TcPO2
timeFrame: 6 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Emmerich
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Joseph Emmerich
role: PRINCIPAL_INVESTIGATOR
References:
citation: HoWangYin KY, Loinard C, Bakker W, Guerin CL, Vilar J, d'Audigier C, Mauge L, Bruneval P, Emmerich J, Levy BI, Pouyssegur J, Smadja DM, Silvestre JS. HIF-prolyl hydroxylase 2 inhibition enhances the efficiency of mesenchymal stem cell-based therapies for the treatment of critical limb ischemia. Stem Cells. 2014 Jan;32(1):231-43. doi: 10.1002/stem.1540.
citation: Smadja DM, Duong-van-Huyen JP, Dal Cortivo L, Blanchard A, Bruneval P, Emmerich J, Gaussem P. Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia. Cytotherapy. 2012 Feb;14(2):232-9. doi: 10.3109/14653249.2011.627917. Epub 2011 Oct 31.
citation: Smadja DM, d'Audigier C, Guerin CL, Mauge L, Dizier B, Silvestre JS, Dal Cortivo L, Gaussem P, Emmerich J. Angiogenic potential of BM MSCs derived from patients with critical leg ischemia. Bone Marrow Transplant. 2012 Jul;47(7):997-1000. doi: 10.1038/bmt.2011.196. Epub 2011 Oct 10. No abstract available.
citation: Smadja DM, d'Audigier C, Bieche I, Evrard S, Mauge L, Dias JV, Labreuche J, Laurendeau I, Marsac B, Dizier B, Wagner-Ballon O, Boisson-Vidal C, Morandi V, Duong-Van-Huyen JP, Bruneval P, Dignat-George F, Emmerich J, Gaussem P. Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties. Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):551-9. doi: 10.1161/ATVBAHA.110.220624. Epub 2010 Dec 9.