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

Evaluation the Side Effects of Repeated Bone Marrow Derived Mono Nuclear Stem Cells Transplantation in Patients With Lower Limb Ischemic Ulcer

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Ulcer
• Intervention / Treatment: Biological: 4times injection; Biological: stem cell transplantation

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Royan Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 62 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4times injection; the patients with ischemic lower limb ulcer who underwent 4times stem cell injection.	Biological: 4times injection; bone marrow derived mono nuclear stem cell
Experimental: one injection; Patients with peripheral artery disease underwent cell transplantation just one time.	Biological: stem cell transplantation; Mono nuclear stem cell transplantation by intra muscular injection to the ischemic lower limb

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: mohammad zafarghandi, MD, Surgery scientist; Principal Investigator: Behnam Molavi, MD, Surgery scientist

Publications and helpful links

General Publications

• Molavi B, Zafarghandi MR, Aminizadeh E, Hosseini SE, Mirzayi H, Arab L, Baharvand H, Aghdami N. Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial. Arch Iran Med. 2016 Jun;19(6):388-96.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: November 23, 2011
• First Submitted That Met QC Criteria: November 25, 2011
• First Posted (Estimate): November 28, 2011

Study Record Updates

• Last Update Posted (Estimate): December 27, 2012
• Last Update Submitted That Met QC Criteria: December 25, 2012
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: bone marrow mono nuclear stem cell ischemic ulcer
• Additional Relevant MeSH Terms: Pathologic Processes; Ulcer; Ischemia
• Other Study ID Numbers: Royan-PVD-002