Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy

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

Study Overview

• Status: Unknown
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Biological: Mesenchymal stem cells; Biological: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Mikhail A Konoplyannikov, PhD; Phone Number: +79154027268; Email: mkonopl@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Federal Research Clinical Center of Federal Medical & Biological Agency
    • Contact: Mikhail A Konoplyannikov, PhD; Phone Number: +79154027268; Email: mkonopl@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stem cells; Mesenchymal stem cells, Intramuscular injection	Biological: Mesenchymal stem cells; Intramuscular injection
Placebo Comparator: Normal saline; Normal saline, Intramuscular injection	Biological: Normal saline; Intramuscular injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
• Investigators: Study Director: Vladimir P Baklaushev, MD, PhD, Deputy Director; Principal Investigator: Pavel Yu Orekhov, MD, PhD, Vascular surgeon

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: MSC-CLI/FMBA/001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No