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 - Full Text View

Sponsors and Collaborators:	Royan Institute Tehran University of Medical Sciences
Information provided by:	Royan Institute
ClinicalTrials.gov Identifier:	NCT00677404

Purpose

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.

Condition	Intervention	Phase
Peripheral Vascular Diseases Ischemia	Biological: BM-MNC Biological: BM-MNC and G-CSF	Phase I Phase II

MedlinePlus related topics: Peripheral Arterial Disease Vascular Diseases

Drug Information available for: Granulocyte colony-stimulating factor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Evaluation of Clinical Outcome in Advanced Chronic Lower Limb Ischemia by Stem Cell Transplantation With or Without (Granulocyte-Colony Stimulation Factor) G-CSF Injection

Further study details as provided by Royan Institute:

Primary Outcome Measures:

Major amputation [ Time Frame: six months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Minor amputation [ Time Frame: six months ] [ Designated as safety issue: Yes ]
Number and extent of leg ulcers [ Time Frame: six months ] [ Designated as safety issue: No ]
Resolvement of rest pain [ Time Frame: six months ] [ Designated as safety issue: No ]
Improvement of ankle-brachial index (ABI) [ Time Frame: six months ] [ Designated as safety issue: No ]
Improvement of pain free walking distances ( PFWD) [ Time Frame: six months ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	January 2008
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental BM-MNC	Biological: BM-MNC Bone marrow aspiration A total volume of 400 ml bone marrow will be aspirated from the iliac crest under epidural anaesthesia
2: Experimental BM-MNC and G-CSF	Biological: BM-MNC and G-CSF Bone marrow aspiration A total volume of 400 ml bone marrow will be aspirated from the iliac crest under epidural anaesthesia and Subcutaneous injection of G-CSF (10 microgr/day) from day of cell injection for 5 days

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Presence of Critical Limb ischemia according to the guidelines of the Transatlantic Consensus Group (TASC) Rutherford grade II or III. Perfusion is measured with absolute perfusion pressure and ankle-brachial index (ABI) and transcutaneous oxygen tension (TcpO2); for inclusion, ABI has to be less than or equal to 0.6 or absolute ankle pressure must be less than 60 mmHg. If ABI is technically not feasible, e.g. in patients with media calcification, inclusion criteria are a tcpO2 value (supine, forefoot, 44°C) of less than 20 mmHg if there is no tissue loss, or a tcpO2 of less than 40 mmHg if there is tissue loss.
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677404

Contacts

Contact: Nasser Aghdami, MD., PhD	98-21-2630-0017	Nasser.aghdami@royaninstitute.org
Contact: Hassan Ravari, MD	98-21-6673-5018	hassanravari@yahoo.com

Locations

Iran, Islamic Republic of
Royan Institute	Recruiting
Tehran, Iran, Islamic Republic of, 1665659911
Contact: Nasser Aghdami, MD., PhD 98-21-2630-0017 Nasser.aghdami@ki.se
Sub-Investigator: Mehrnaz Namiri, Ms
Tehran University of medical sciences, Vascular Surgery department, Sina Hospital	Recruiting
Tehran, Iran, Islamic Republic of
Contact: Hassan Ravari, MD 98-21-6673-5018 hassanravari@yahoo.com

Sponsors and Collaborators

Royan Institute

Tehran University of Medical Sciences

Investigators

Study Chair:	Hamid Gorabi, PhD	Royan institute, Tehran, Iran
Study Chair:	Mohammad reza Zafarghandi, MD	Sina Hospital, Tehran, Iran
Study Director:	Nasser Aghdami, MD., PhD	Royan institute, Tehran, Iran
Principal Investigator:	Hossein Baharvand, PhD	Royan institute, Tehran, Iran
Principal Investigator:	Hassan Ravari, MD	Sina Hospital, Tehran, Iran

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	Royan Institute ( Hamid Gourabi, Chief )
Study ID Numbers:	Royan-PVD-001
Study First Received:	May 12, 2008
Last Updated:	July 9, 2008
ClinicalTrials.gov Identifier:	NCT00677404
Health Authority:	Iran: Ministry of Health

Keywords provided by Royan Institute:

Peripheral vascular diseases
chronic lower limb ischemia

Study placed in the following topic categories:

Peripheral Vascular Diseases
Vascular Diseases
Ischemia

Additional relevant MeSH terms:

Pathologic Processes
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 14, 2009