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

NCT ID: NCT00677404

Last Updated: 2011-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-01-31

Brief 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

Keywords

Peripheral vascular diseases; chronic lower limb ischemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

stem cell recipient

the patients with peripheral vascular disease who receive bone marrow derived mono nuclear cells

Group Type: EXPERIMENTAL

BM-MNC injection

Intervention Type: BIOLOGICAL

Bone marrow aspiration A total volume of 400 ml bone marrow will be aspirated from the iliac crest under epidural anaesthesia

Interventions

BM-MNC injection

Bone marrow aspiration A total volume of 400 ml bone marrow will be aspirated from the iliac crest under epidural anaesthesia

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• No sufficient response to best standard care delivered for six weeks.
• No surgical or radiological interventional option for revascularisation as confirmed by a vascular surgeon and an interventional radiologist
• Signed informed consent
• Absence of life-threatening complications from the ischemic limb

Exclusion Criteria

• Expected life span less than six months
• Bone marrow diseases which preclude transplantation (eg lymphoma, leukaemia, myelodysplastic syndrome and others)
• Patients with poorly controlled diabetes mellitus (HbA1C > 8%)
• Patients with renal insufficiency (creatinine > 2.5).
• Patients with evidence of infectious disease as determined by e. above or other medical findings.
• Pregnant women (women capable of childbearing must have a negative pregnancy test).
• Patients with cognitive impairments.
• Other comorbid disease that would be expected to result in less than one year life expectancy
• Past malignancy or history of chemotherapy or radiation affecting the bone marrow.
• History of inflammatory or progressively fibrotic conditions: .e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis
• Infection as evidenced by WBC count of >15,000 and/or temperature more than 38C. Large area of cellulitis in the afflicted limb that in the opinion ofthe investigators would require the institution of antibiotics OR evidence of osteomyelitis corroborated by radiographic or scintigraphic examination
• Cardiovascular conditions:
• EF<30%
• Acute ST elevation myocardial infarction (MI) within 1month;
• Transient ischemic attack or stroke within 1 month;
• Severe valvular disease
• CVA
• Patients with any history of organ transplants

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tehran University of Medical Sciences

OTHER

Sponsor Role: collaborator

Royan Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Royan Institute

Principal Investigators

Hamid Gorabi, PhD

Role: STUDY_CHAIR

Royan institute, Tehran, Iran

Mohammad reza Zafarghandi, MD

Role: STUDY_CHAIR

Sina Hospital, Tehran, Iran

Nasser Aghdami, MD., PhD

Role: STUDY_DIRECTOR

Royan institute, Tehran, Iran

Hossein Baharvand, PhD

Role: PRINCIPAL_INVESTIGATOR

Royan institute, Tehran, Iran

Hassan Ravari, MD

Role: PRINCIPAL_INVESTIGATOR

Sina Hospital, Tehran, Iran

Locations

Royan Institute

Tehran, Tehran Province, Iran

Tehran University of medical sciences, Vascular Surgery department, Sina Hospital

Tehran, Tehran Province, Iran

Countries

Iran

References

Zafarghandi MR, Ravari H, Aghdami N, Namiri M, Moazzami K, Taghiabadi E, Fazel A, Pournasr B, Farrokhi A, Sharifian RA, Salimi J, Moini M, Baharvand H. Safety and efficacy of granulocyte-colony-stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia. Cytotherapy. 2010 Oct;12(6):783-91. doi: 10.3109/14653240903518163.

Reference Type: RESULT

PMID: 20078390 (View on PubMed)

Related Links

http://www.royaninstitute.org

Related Info

Other Identifiers

Royan-PVD-001

Identifier Type: -

Identifier Source: org_study_id