Side Effects of 4 Times Bone Marrow Mono Nuclear Transplantation in Patients With Ischemic Lower Limb

Phase 1

Completed

• Conditions: Ischemic Ulcer
• Interventions: Biological: 4times injection; Biological: stem cell transplantation

• Registration Number: NCT01480414
• Lead Sponsor: Royan Institute

Brief Summary

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 the investigators 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. Indeed, recent studies have shown that bone-marrow mononuclear cell (BM-MNC) implantation increases collateral vessel formation in patients with limb ischemia. So the investigators determine to evaluate the efficacy of repeated MNC transplantation in patients with ischemic lower limb.

Detailed Description

In this study we transparent bone marrow derived mononuclear stem cells 4 times to the ischemic limb of 11 patients with PAD.first of all all the patients evaluate by physical examination,PFWD,ABI and serologic tests.then underwent bone marrow aspiration to take sample.In our lab the MNC are separated and divided in to equal doses.one of them inject to the ischemic foot and the othr one are freezed and inject after 3weeks.3 weeks after second injection again patient underwent bone marrow aspiration and the same process repeat.then after 4times transplantation,patients are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.all the data are collected and analysed and the result will be shown.3 patients underwent cell transplantation just one time due to one time bone marrow aspiration.They are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.at the end of the study patients with 4imes injection and 1time injection will be compared.

Study Timeline

• Status Verified: 2010-07
• Study Start: 2010-09
• Study First Submitted: 2011-11-23
• Study First Submitted QC: 2011-11-25
• Study First Posted: 2011-11-28
• Primary Completion: 2012-04
• Study Completion: 2012-05
• Last Update Submitted: 2012-12-25
• Last Update Posted: 2012-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Ischemic lower limb based on TASK guide line
• Rutherford score:2,3
• ABI<0.6
• Absolute ankle pressure < 60 mmHg
• Both gender
• Age:20-62years

Exclusion Criteria

• EF<30%
• Cr>2
• HbA1c>8%
• Bone marrow disorders:leukemia
• Cognitive disorders
• Infections
• MI with ST elevation during last month
• Malignancy
• Immunologic or rheumatologic disorders

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4times injection	4times injection	the patients with ischemic lower limb ulcer who underwent 4times stem cell injection.
one injection	stem cell transplantation	Patients with peripheral artery disease underwent cell transplantation just one time.

Primary Outcome Measures

Name	Time	Method
side effects	3months	evaluation the side effect of cell injection like:allergic reaction,fever,skin eruption,pain increasing,decrease in walking distance,ulcer severity

Secondary Outcome Measures

Name	Time	Method
PFWD	3months	Evaluation the pain free walking distance after cell transplantation.
ABI	3months	evaluation the improvement the score of ABI after stem cell transplantation .
size and depth of ulcer	3months	evaluation the improvement of ulcer by measuring the size and depth of ulcer in millimeter after transplantation.
Amputation	6months	Evaluation the need of limb amputation because of worsening the ulcer after cell injection.

Trial Locations

Locations (1)

Royan Institute; 🇮🇷 Tehran, Iran, Islamic Republic of