Intramuscular Mononuclear Cells and Mesenchymal Stem Cells Transplantation to Treat Chronic Critical Limb Ischemia

Phase II Efficacy Study of Intramuscular Autologous Bone Marrow Mononuclear Cells Plus Mesenchymal Stem Cell Implantation Versus Autologous Bone Marrow Mononuclear Cells Implantation Only in Patients With Chronic Critical Limb Ischemia

This is a randomized and single blinded study aimed to compare the efficacy between intramuscular autologous bone marrow mononuclear cells plus mesenchymal stem cell implantation and intramuscular autologous bone marrow mononuclear cells implantation only in patients with chronic critical limb ischemia. Patients will be randomized into two groups of equal number; patients in one group will be implanted with mononuclear cells and mesenchymal stem cells, and the other implanted with mononuclear cells only in the area of affected limb.

Study Overview

• Status: Unknown
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Biological: Mononuclear and mesenchymal stem cells; Biological: Mononuclear cells

Detailed Description

When the long blood vessels supplying blood to the arms and legs become blocked (ischemic), patient will experience painful sensations in their calves when they walked which slowly become excruciating painful at rest. When the condition worsens, the patients will not be able to feel any pain from their legs and they will not know if there are any small ulcers or cuts on their legs. As a result, a small ulcer which goes unnoticed becomes bigger and can sometimes become infected. In the worst situations, infection might lead towards gangrene and septicaemia. Severe rest pain and/or ulcerations of ischemic limbs are defined as the state of chronic critical limb ischemia and at this point, amputation of the affected limb is suggested.

Conventional treatments include angioplasty/bypass operation to remove blood vessel blockage to restore blood supply, the use of prescribed medicines to aid in ulcer recovery and clear infection and debridement of damaged/infected tissue. Some procedures have to be performed multiple times. Amputation is inevitable in many cases because some blood capillaries cannot be corrected and restenosis of vessels is very common. Cell therapy with mononuclear cells and mesenchymal stem cells from bone marrow is promising because these stem cells are capable of stimulating and regenerating capillaries and blood vessels.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hanafiah Harunarashid, MD; Phone Number: +60391456208; Email: hanafiah@ppukm.ukm.my

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 56000
    • Recruiting
    • UKM Medical Centre
    • Contact: Hanafiah Harunarashid, MD
    • Principal Investigator: Hanafiah Harunarashid, MD
    • Sub-Investigator: Mohammad Azim Mohammad Idris, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of critical limb ischemia leading to ischemic ulcers in which amputation is indicated
• Not suitable for, or remain symptomatic despite angioplasty, bypass operation or collateralization

Exclusion Criteria:

• Contraindication to epidural anesthesia and bone marrow aspiration
• Contraindication to contrast angiography
• Evidence of neoplasia and bone marrow diseases
• Any acute or chronic communicable diseases including Hepatitis B, Hepatitis C and HIV
• Patients with a limited life expectancy (< 1 year)
• Patients with myocardial infarction or stroke within 6 months
• Patients with coronary intervention within 6 months
• Renal impairment indicated by serum creatinine greater than two times upper limit of the normal range
• Liver impairment indicated by serum aspartate transaminase and alanine transaminase greater than two times upper limit of normal
• Any other co-morbidity which the physician deems as a contraindication to stem cell transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mononuclear and mesenchymal stem cells; Autologous bone marrow-derived mononuclear cells and mesenchymal stem cells	Biological: Mononuclear and mesenchymal stem cells; Intramuscular administration into the ischemic limb; Other Names: BM-MNC and BM-MSC
Active Comparator: Mononuclear cells only; Autologous bone marrow-derived mononuclear cells	Biological: Mononuclear cells; Intramuscular administration into the ischemic limb; Other Names: BM-MNC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in angiogenesis	Measurement of angiogenesis by presence of peripheral pulses, capillary refill and transcutaneous oxygen saturation (TCOS).	1 month, 3 months, 6 months, 9 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Score		1 month, 3 months, 6 months, 9 months, 12 months
Change in ulcer size	Measurement of ulcer size by clinical assessment and grid maps.	1 month, 3 months, 6 months, 9 months, 12 months
Exercise Treadmill Test		1 month, 3 months, 6 months, 9 months, 12 months
Improvement in vascularity and blood supply	Measured by digital subtraction angiography (DSA) and ankle brachial systemic pressure index (ABI).	1 month, 3 months, 6 months, 9 months and 12 months

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Cytopeutics Sdn. Bhd.
• Investigators: Principal Investigator: Hanafiah Harunarashid, MD, UKM Medical Centre

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: October 4, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 21, 2011

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: efficacy; bone marrow; critical limb ischemia; mesenchymal stem cells; autologous; mononuclear cells
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: FF-113-2011; NMRR-11-904-9763 (Registry Identifier: National Medical Research Register)