Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy

Study Overview
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Brief Summary
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The clinical trial aims to study the safety and efficacy of adult allogeneic mesenchymal stem cells for the treatment of critical limb ischemia.

Official Title
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Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy

Conditions
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Critical Limb Ischemia

Intervention / Treatment
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* Biological: Mesenchymal stem cells
* Biological: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females in the age group of 18-80 yrs of Caucasian origin. Peripheral artery disease (PAD) against the background of atherosclerosis and diabetes mellitus (DM) Critical lower limb ischemia (stages 3-4 by Fontaine-Pokrovsky or stages 4-6 by Rutherford) Patients with remaining symptoms of critical limb ischemia (CLI) in spite of the performed surgical (endovascular or open) treatment and continuing conservative therapy Patients with absent emergency indications to major amputation Patients planned for the reconstructive surgery with a questionable remote outcome due to compromised blood outflow Ankle Brachial Pressure Index (ABPI) ≤ 0.5 or ankle pressure ≤ 70 mm Hg Patients, if having associated Type II Diabetes, should be on medication and well controlled (HbA1c ≤ 8.5 %) On regular medication for hypertension if needed Normal liver and renal function (or having clinically insignificant deviations, according to the treating physician's opinion) Patients who are able to understand the requirements of the study, and willing to provide voluntary written informed consent, abide by the study requirements, and agree to return for required follow-up visits Exclusion Criteria: Humid gangrene or acute/chronic infection of lower limb. Dry gangrene with extensive foot lesion (> 1\2). Acute arterial failure. Life-threatening conditions and predicted life expectancy of < 6 months. Presence of neoplasm or bone marrow disease Signs of active or chronic, including latent, haemorrhage Any acute or chronic infectious disease Renal failure determined as twofold or higher elevation of serum creatinine as compared to the upper normal limit Hepatic failure determined as the bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels elevated by two and more times over the upper normal limits Thrombocytopenia (platelet counts < 50,000 /µl), leukocytopenia (WBC < 4,000/µl), immunosuppressive therapy Pronounced neurological deficit Patients with gait disturbance for reasons other than CLI Patients not suitable for cell therapy, by the treating physician's opinion CLI patients requiring amputation at the proximal to the trans-metatarsal level Patients with Type I diabetes Patients having respiratory complications/left ventricular ejection fraction < 25% Stroke or myocardial infarction within last 3 months Patients who are contraindicated for X-ray angiography History of severe alcohol or drug abuse within 3 months of screening Pregnant and lactating women. Patients tested positive for HIV 1, hepatitis C virus (HCV), hepatitis B virus (HBV) Unsigned informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells<br>Mesenchymal stem cells, Intramuscular injection | Biological: Mesenchymal stem cells<br>* Intramuscular injection<br>|
| Placebo Comparator: Normal saline<br>Normal saline, Intramuscular injection | Biological: Normal saline<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of adverse events reported | 24 months | 
| Amputation-free survival | Number of survived patients | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Limb salvage from major amputation | Number of patients who avoided amputation | 3, 6, 12, 24 months | 
| Relief of the rest pain | Rest pain will be measured using the rest pain scale | Immediate, 3, 6, 12, 24 months | 
| Improvement in healing trophic disorders | Assessment of the severity of trophic ulcers | Immediate, 3, 6, 12, 24 months | 
| Improvement in perfusion by the ankle-brachial index | Measurements of the ankle-brachial index | Immediate, 3, 6, 12, 24 months | 
| Improvement in perfusion by radioisotope scintigraphy | Radioisotope scintigraphy study | Immediate, 3, 6, 12, 24 months | 
| Improvement in total walking distance (TWD) using a standard treadmill test | Standard treadmill test | Immediate, 3, 6, 12, 24 months |