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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by National University of Malaysia.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Cytopeutics Pte. Ltd.
Information provided by (Responsible Party):
Dr Hanafiah Harunarashid, National University of Malaysia
ClinicalTrials.gov Identifier:
NCT01456819
First received: October 4, 2011
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

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.

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.


Condition Intervention Phase
Critical Limb Ischemia
Biological: Mononuclear and mesenchymal stem cells
Biological: Mononuclear cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by National University of Malaysia:

Primary Outcome Measures:
  • Change in angiogenesis [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]
    Measurement of angiogenesis by presence of peripheral pulses, capillary refill and transcutaneous oxygen saturation (TCOS).

  • Change in blood supply [ Time Frame: 1 month, 12 months ] [ Designated as safety issue: Yes ]
    Measurement of blood supply by digital subtraction angiography (DSA) and ankle brachial systemic pressure index (ABI).


Secondary Outcome Measures:
  • Change in ulcer size [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]
    Measurement of ulcer size by clinical assessment and grid maps.

  • Visual Analog Score [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]
  • Exercise Treadmill Test [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: March 2011
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mononuclear & 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 Name: 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 Name: BM-MNC

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01456819

Contacts
Contact: Hanafiah Harunarashid, MD +60391456208 hanafiah@ppukm.ukm.my

Locations
Malaysia
UKM Medical Centre Recruiting
Kuala Lumpur, Malaysia, 56000
Contact: Hanafiah Harunarashid, MD         
Principal Investigator: Hanafiah Harunarashid, MD         
Sub-Investigator: Mohammad Azim Mohammad Idris, MD         
Sponsors and Collaborators
National University of Malaysia
Cytopeutics Pte. Ltd.
Investigators
Principal Investigator: Hanafiah Harunarashid, MD UKM Medical Centre
  More Information

No publications provided

Responsible Party: Dr Hanafiah Harunarashid, Senior Consultant Vascular Surgeon, National University of Malaysia
ClinicalTrials.gov Identifier: NCT01456819     History of Changes
Other Study ID Numbers: FF-113-2011, NMRR-11-904-9763
Study First Received: October 4, 2011
Last Updated: February 16, 2012
Health Authority: Malaysia: Institutional Review Board
Malaysia: Ministry of Health

Keywords provided by National University of Malaysia:
autologous
bone marrow
critical limb ischemia
efficacy
mesenchymal stem cells
mononuclear cells

Additional relevant MeSH terms:
Ischemia
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014