Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy

Phase 1

• Conditions: Critical Limb Ischemia
• Interventions: Biological: Normal saline; Biological: Mesenchymal stem cells

• Registration Number: NCT03239535
• Lead Sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10-01
• Study First Submitted: 2017-07-20
• Status Verified: 2017-08
• Study First Submitted QC: 2017-08-01
• Last Update Submitted: 2017-08-01
• Study First Posted: 2017-08-04
• Last Update Posted: 2017-08-04
• Primary Completion: 2018-08-01
• Study Completion: 2018-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Males or females in the age group of 18-80 yrs of Caucasian origin.
2. Peripheral artery disease (PAD) against the background of atherosclerosis and diabetes mellitus (DM)
3. Critical lower limb ischemia (stages 3-4 by Fontaine-Pokrovsky or stages 4-6 by Rutherford)
4. Patients with remaining symptoms of critical limb ischemia (CLI) in spite of the performed surgical (endovascular or open) treatment and continuing conservative therapy
5. Patients with absent emergency indications to major amputation
6. Patients planned for the reconstructive surgery with a questionable remote outcome due to compromised blood outflow
7. Ankle Brachial Pressure Index (ABPI) ≤ 0.5 or ankle pressure ≤ 70 mm Hg
8. Patients, if having associated Type II Diabetes, should be on medication and well controlled (HbA1c ≤ 8.5 %)
9. On regular medication for hypertension if needed
10. Normal liver and renal function (or having clinically insignificant deviations, according to the treating physician's opinion)
11. 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

1. Humid gangrene or acute/chronic infection of lower limb.
2. Dry gangrene with extensive foot lesion (> 1\2).
3. Acute arterial failure.
4. Life-threatening conditions and predicted life expectancy of < 6 months.
5. Presence of neoplasm or bone marrow disease
6. Signs of active or chronic, including latent, haemorrhage
7. Any acute or chronic infectious disease
8. Renal failure determined as twofold or higher elevation of serum creatinine as compared to the upper normal limit
9. 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
10. Thrombocytopenia (platelet counts < 50,000 /µl), leukocytopenia (WBC < 4,000/µl), immunosuppressive therapy
11. Pronounced neurological deficit
12. Patients with gait disturbance for reasons other than CLI
13. Patients not suitable for cell therapy, by the treating physician's opinion
14. CLI patients requiring amputation at the proximal to the trans-metatarsal level
15. Patients with Type I diabetes
16. Patients having respiratory complications/left ventricular ejection fraction < 25%
17. Stroke or myocardial infarction within last 3 months
18. Patients who are contraindicated for X-ray angiography
19. History of severe alcohol or drug abuse within 3 months of screening
20. Pregnant and lactating women.
21. Patients tested positive for HIV 1, hepatitis C virus (HCV), hepatitis B virus (HBV)
22. Unsigned informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal saline	Normal saline	Normal saline, Intramuscular injection
Mesenchymal stem cells	Mesenchymal stem cells	Mesenchymal stem cells, Intramuscular injection

Primary Outcome Measures

Name	Time	Method
Adverse events	24 months	Number of adverse events reported
Amputation-free survival	24 months	Number of survived patients

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Federal Research Clinical Center of Federal Medical & Biological Agency; 🇷🇺 Moscow, Russian Federation