Clinical trial NCT01456819: Intramuscular Mononuclear Cells and Mesenchymal Stem Cells Transplantation to Treat Chronic Critical Limb Ischemia
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Critical Limb Ischemia
Keywords: autologous
bone marrow
critical limb ischemia
efficacy
mesenchymal stem cells
mononuclear cells
Lead sponsor: National University of Malaysia
Sponsor class: OTHER
Collaborators: name: Cytopeutics Sdn. Bhd.
First posted: 2011-10-21
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Change in angiogenesis
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
Secondary outcomes:
measure: Change in ulcer size
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Visual Analog Score
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Exercise Treadmill Test
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Improvement in vascularity and blood supply
timeFrame: 1 month, 3 months, 6 months, 9 months and 12 months
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: UKM Medical Centre
Study officials:
affiliation: UKM Medical Centre
name: Hanafiah Harunarashid, MD
role: PRINCIPAL_INVESTIGATOR
References: