Clinical trial NCT03239535: Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy
Official title: Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Critical Limb Ischemia
Lead sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Sponsor class: OTHER_GOV
First posted: 2017-08-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: 24 months
measure: Amputation-free survival
timeFrame: 24 months
Secondary outcomes:
measure: Limb salvage from major amputation
timeFrame: 3, 6, 12, 24 months
measure: Relief of the rest pain
timeFrame: Immediate, 3, 6, 12, 24 months
measure: Improvement in healing trophic disorders
timeFrame: Immediate, 3, 6, 12, 24 months
measure: Improvement in perfusion by the ankle-brachial index
timeFrame: Immediate, 3, 6, 12, 24 months
measure: Improvement in perfusion by radioisotope scintigraphy
timeFrame: Immediate, 3, 6, 12, 24 months
measure: Improvement in total walking distance (TWD) using a standard treadmill test
timeFrame: Immediate, 3, 6, 12, 24 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal Research Clinical Center of Federal Medical & Biological Agency
Study officials:
affiliation: Deputy Director
name: Vladimir P Baklaushev, MD, PhD
role: STUDY_DIRECTOR
affiliation: Vascular Surgeon
name: Pavel Yu Orekhov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: