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

Critical Limb Ischemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01456819
• Other study ID #: FF-113-2011
• Secondary ID: NMRR-11-904-9763
• Status: Recruiting
• Phase: Phase 2
• First received: October 4, 2011
• Last updated: April 9, 2015
• Start date: March 2011
• Est. completion date: February 2016

Study information

• Verified date: April 2015
• Source: National University of Malaysia
• Contact: Hanafiah Harunarashid, MD
• Phone: +60391456208
• Email: hanafiah[@]ppukm.ukm.my
• Is FDA regulated: No
• Health authority: Malaysia: Institutional Review BoardMalaysia: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Ischemia

Intervention

Biological:
• Mononuclear and mesenchymal stem cells
Intramuscular administration into the ischemic limb
• Mononuclear cells
Intramuscular administration into the ischemic limb

Locations

Country	Name	City	State
Malaysia	UKM Medical Centre	Kuala Lumpur

Sponsors (2)

Lead Sponsor	Collaborator
National University of Malaysia	Cytopeutics Sdn Bhd

Country where clinical trial is conducted

Malaysia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Change in ulcer size	Measurement of ulcer size by clinical assessment and grid maps.	1 month, 3 months, 6 months, 9 months, 12 months	Yes
Secondary	Visual Analog Score		1 month, 3 months, 6 months, 9 months, 12 months	Yes
Secondary	Exercise Treadmill Test		1 month, 3 months, 6 months, 9 months, 12 months	Yes
Secondary	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	Yes