Cell Therapy in Chronic Limb Ischemia

This study has been completed.
Sponsor:
Information provided by:
CHU de Reims
ClinicalTrials.gov Identifier:
NCT00533104
First received: September 19, 2007
Last updated: February 5, 2009
Last verified: February 2009

September 19, 2007
February 5, 2009
October 2004
February 2009   (final data collection date for primary outcome measure)
Survival without major amputation [ Time Frame: 6 months after implantation ]
Survival without major amputation [ Time Frame: 6 months after implatation ]
Complete list of historical versions of study NCT00533104 on ClinicalTrials.gov Archive Site
clinical symptoms and haemodynamic parameters [ Time Frame: Within 6 months after implantation ]
clinical symptoms and haemodynamic parameters [ Time Frame: Within 6 months after implatation ]
Not Provided
Not Provided
 
Cell Therapy in Chronic Limb Ischemia
Critical Limb Ischemia Treatment by Local Intra-Muscular Injection of Autologous Mononuclear Cells

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.

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.

The 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.

Before implantation, MNC counts, differential and viability are determined. CD34+, CD34+/CD133+ and CD34+/CD133+/flk-1+ cells are counted by flow-cytometry.

Clinical 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

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Peripheral Vascular Diseases
  • Procedure: BM-MNC preparation

    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.

    Cells 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).

  • Procedure: PB-MNC preparation

    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.

    Cells 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).

  • Experimental: BM-MNC
    Patients are implanted with bone marrow - mononuclear cells
    Intervention: Procedure: BM-MNC preparation
  • Experimental: PB-MNC
    Patients are implanted with peripheral blood - mononuclear cells
    Intervention: Procedure: PB-MNC preparation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
February 2009
February 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with unilateral critical chronic limb ischemia but not suitable candidates for non-surgical or surgical revascularization
  • Before being included, the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, treponema pallidum

Exclusion Criteria:

  • Buerger disease
  • Ischemic ulcers with infectious symptoms
  • Diabetes mellitus with HbA1c > 7,5% or with proliferative retinopathy
  • Past or current malignancy
  • Contra-indication to general anaesthesia
  • Chronic haemodialysis
  • Prothrombin Time < 60%,
  • Recent onset (within 3 months) of myocardial infarction or brain infarction
  • Coronary angioplasty within 1 year
  • Atrial fibrillation, mechanical mitral prosthetic valve
  • Unexplained hematological abnormality.
  • Expected life span less than six months
  • Patient not competent to give informed consent
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00533104
PHRC Région 2003 / R11-05 / 95
Yes
PIGNON / MD, Centre Hospitalier Universitaire de REIMS - FRANCE
CHU de Reims
Not Provided
Study Director: Bernard PIGNON, MD University Hospital REIMS FRANCE
Principal Investigator: Marie-Antoinette SEVESTRE, MD University Hospital AMIENS FRANCE
CHU de Reims
February 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP