NCT00677404

Autologous Transplantation of Bone Marrow Mononuclear Cell (BM-MNC) With and Without Granulocyte-Colony Stimulation Factor (G-CSF) for Treatment of Chronic Lower Limb Ischemic Patients

Evaluation of Clinical Outcome in Advanced Chronic Lower Limb Ischemia by Stem Cell Transplantation With or Without (Granulocyte-colony Stimulation Factor) G-CSF Injection

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Royan Institute · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to investigate the efficacy and safety of autologous transplantation of mononuclear cells with and without G-CSF in patients with chronic lower limb ischemia.

Detailed description

Critical limb ischemia (CLI) results from severe occlusive disease that impairs distal limb perfusion to the point where oxygen delivery is no longer adequate to meet the metabolic needs of the tissue, even under resting conditions. The limits of peripheral artery disease (PAD) compensatory mechanisms, such as distal vasodilatation and collateral formation, have been exceeded at this point. PAD is a widespread disease, affecting up to 15% of all adults older than 55 years. Formation of true new blood vessels, or angiogenesis, and development of collateral vessels from preexisting blood vessels, or arteriogenesis, is important in the pathophysiology of vascular disease. By stimulating these processes we might be able to provide an alternative treatment strategy for patients with lower limb ischemia. In response to tissue injury and remodeling, neovascularization usually occurs via the proliferation and migration of progenitor endothelial cells (EPC) from preexisting vasculature. The EPCs resident within bone marrow and peripheral blood, so it seems implantation of BM cells can contribute to injury-induced and pathology induced neovascularization. Indeed, recent studies have shown that bone-marrow mononuclear cell (BM-MNC) implantation increases collateral vessel formation in both ischemic limb models and patients with limb ischemia. In addition, granulocyte-colony stimulation factor could mobilize the EPCs to peripheral blood. After BM-MNC implantation, G-CSF can contribute more EPC in PB for effective angiogenesis in PAD patients. In this study, Bone marrow puncture will be performed in a common manner. The iliac crest is punctured under epidural anesthesia and 400 mL of bone marrow will be aspirated. The MNCs are isolated under good manufacturing practice conditions by Ficoll density separation and is intramuscularly injected (40 sites, in 3 × 3 cm distance, 1-1.5 cm deep, into ischemic leg. In some patients G-CSF (10 microgr/day) is administration by subcutaneous injection from day of cell injection for 5 days.

Conditions

• Peripheral Vascular Diseases
• Ischemia

Interventions

Type	Name	Description
BIOLOGICAL	BM-MNC injection	Bone marrow aspiration A total volume of 400 ml bone marrow will be aspirated from the iliac crest under epidural anaesthesia

Timeline

• Start date: 2008-01-01
• Primary completion: 2009-10-01
• Completion: 2010-01-01
• First posted: 2008-05-14
• Last updated: 2011-07-29

Locations

2 sites across 1 country: Iran