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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Royan Institute
ClinicalTrials.gov Identifier:
NCT01480414
First received: November 23, 2011
Last updated: December 25, 2012
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Ischemic Ulcer
Biological: 4times injection
Biological: stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation the Side Effects of Repeated Bone Marrow Derived Mono Nuclear Stem Cells Transplantation in Patients With Lower Limb Ischemic Ulcer

Further study details as provided by Royan Institute:

Primary Outcome Measures:
  • side effects [ Time Frame: 3months ] [ Designated as safety issue: Yes ]
    evaluation the side effect of cell injection like:allergic reaction,fever,skin eruption,pain increasing,decrease in walking distance,ulcer severity


Secondary Outcome Measures:
  • PFWD [ Time Frame: 3months ] [ Designated as safety issue: No ]
    Evaluation the pain free walking distance after cell transplantation.

  • ABI [ Time Frame: 3months ] [ Designated as safety issue: Yes ]
    evaluation the improvement the score of ABI after stem cell transplantation .

  • size and depth of ulcer [ Time Frame: 3months ] [ Designated as safety issue: Yes ]
    evaluation the improvement of ulcer by measuring the size and depth of ulcer in millimeter after transplantation.

  • Amputation [ Time Frame: 6months ] [ Designated as safety issue: No ]
    Evaluation the need of limb amputation because of worsening the ulcer after cell injection.


Enrollment: 20
Study Start Date: September 2010
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   20 Years to 62 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01480414

Locations
Iran, Islamic Republic of
Royan Institute
Tehran, Iran, Islamic Republic of
Sponsors and Collaborators
Royan Institute
Investigators
Study Chair: Hamid Gourabi, PhD Head of Royan Institute
Study Director: mohammad zafarghandi, MD surgery scientist
Study Director: Nasser Aghdami, MD,PhD head of Royan cell therapy center
Principal Investigator: Behnam Molavi, MD Surgery scientist
  More Information

No publications provided

Responsible Party: Royan Institute
ClinicalTrials.gov Identifier: NCT01480414     History of Changes
Other Study ID Numbers: Royan-PVD-002
Study First Received: November 23, 2011
Last Updated: December 25, 2012
Health Authority: Iran: Ethics Committee
Iran: Ministry of Health

Keywords provided by Royan Institute:
bone marrow mono nuclear stem cell ischemic ulcer

Additional relevant MeSH terms:
Ischemia
Ulcer
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014