Safety and Efficacy Study of Autologous Bone Marrow Aspirate Concentrate for No-Option Critical Limb Ischemia

NCT ID: NCT01818310

Last Updated: 2021-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2018-10-31

Brief Summary

The aim of the presented clinical trial is to evaluate a hypothesis, that BMAC prepared from bone marrow aspirate and injected intramuscularly into ischemic areas of the lower extremity in patients with diabetes mellitus type II., intraarterially into the defect of the limb or with an intravenous application only, has a greater potential to improve the perfusion in the ischemic limbs than standard treatment of NO-CLI. Another aim of the study is to find out differences among three different therapeutic types of BMAC application, to define their effectiveness and safety and to compare the impact of different means of application to the speed of healing of the limb defects and the improvement of perfusion parameters.

Detailed Description

Secondary hypothesis assumes, that the intravenous application of BMAC in patients with T2DM older than 30 years of age, with a dose of insulin exceeding 0.7 U/kg/day or 50U/day will result in decreasing the insulin dose in the course of 6-month follow-up and in an improvement of the glycHBA1c levels, improvement of the liver and kidney function, decrease of the cholesterol levels and improvement of the immune response parameters, i.e. parameters of lymphocytar blastic transformation, more than in case of patients with intramuscular or intraarterial application of BMAC.

Conditions

Critical Lower Limb Ischemia; Type-2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group A: Intramuscular

Intramuscular BMAC application The study subjects in the Group A will receive a treatment of 35ml BMAC administered intramuscularly into the affected limb, in individual punctures of 1 ml.

The punctures will be applied into the crural muscle around the defect, the procedure takes approx. 60 minutes.

Group Type: EXPERIMENTAL

Group A: Intramuscular

Intervention Type: BIOLOGICAL

Intramuscular BMAC application The study subjects in the Group A will receive a treatment of 35ml BMAC administered intramuscularly into the affected limb, in individual punctures of 1 ml.

The punctures will be applied into the crural muscle around the defect, the procedure takes approx. 60 minutes.

Group B: Intraarterial

Intraarterial BMAC application The study subjects in the Group B will receive a treatment of 35ml BMAC administered intraarterially into the affected limb.

Group Type: EXPERIMENTAL

Group B: Intraarterial

Intervention Type: BIOLOGICAL

Intraarterial BMAC application The study subjects in the Group B will receive a treatment of 35ml BMAC administered intraarterially into the affected limb.

Group C: Intravenous

Group C: Intravenous The study subjects in the Group C will receive a treatment of 35ml BMAC administered intravenously into the affected limb.

Group Type: EXPERIMENTAL

Group C: Intravenous

Intervention Type: BIOLOGICAL

Group C: Intravenous The study subjects in the Group C will receive a treatment of 35ml BMAC administered intravenously into the affected limb.

Group D: Control-standard treatment

Group D: Control Group Study subjects in Group D will receive a standard treatment for NO-option CLI.

Group Type: OTHER

Group D: Surgical endovascular treatment with maximum medicamentous treatment

Intervention Type: PROCEDURE

Group D: Control Group Control Group - no experimental intervention, standard endovascular treatment or bypass surgery or maximum medicamentous treatment

Interventions

Group A: Intramuscular

Intramuscular BMAC application The study subjects in the Group A will receive a treatment of 35ml BMAC administered intramuscularly into the affected limb, in individual punctures of 1 ml.

The punctures will be applied into the crural muscle around the defect, the procedure takes approx. 60 minutes.

Intervention Type: BIOLOGICAL

Group B: Intraarterial

Intraarterial BMAC application The study subjects in the Group B will receive a treatment of 35ml BMAC administered intraarterially into the affected limb.

Intervention Type: BIOLOGICAL

Group C: Intravenous

Group C: Intravenous The study subjects in the Group C will receive a treatment of 35ml BMAC administered intravenously into the affected limb.

Intervention Type: BIOLOGICAL

Group D: Surgical endovascular treatment with maximum medicamentous treatment

Group D: Control Group Control Group - no experimental intervention, standard endovascular treatment or bypass surgery or maximum medicamentous treatment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• type 2 diabetes mellitus
• diagnosis of critical limb ischemia
• non-healing defect on the study limb
• ABI value < 50 mmHg or ABI< 0.4
• TBI value < 40 mmHg or TBI < 0.4
• TcPO2 < 20 mmHg in supine position
• no other suitable surgical or re-vascularization procedure
• age > 18 years
• signed Informed Consent

Exclusion Criteria

• non-signing of the Informed Consent
• anticipated life expectancy < 6 months
• history of bone-marrow disease
• renal failure or dialysis dependency
• known malignant disease
• health risks excluding the possibility of general anaesthesia or sedation
• life-threatening ischaemic heart disease
• vast necrosis of the index limb
• active infectious disease, or ATB treatment
• treatment with immunosupressives
• pregnancy, breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Czech Republic

OTHER_GOV

Sponsor Role: collaborator

Regional Council of the Moravian-Silesian region, KU MSK

UNKNOWN

Sponsor Role: collaborator

University Hospital Ostrava

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaclav Prochazka, MD, PhD, MSc

Role: PRINCIPAL_INVESTIGATOR

University Hospital Ostrava

Locations

University Hospital Ostrava

Ostrava, , Czechia

Countries

Czechia

References

Dormandy J, Heeck L, Vig S. The natural history of claudication: risk to life and limb. Semin Vasc Surg. 1999 Jun;12(2):123-37.

Reference Type: BACKGROUND

PMID: 10777239 (View on PubMed)

Clair DG, Dayal R, Faries PL, Bernheim J, Nowygrod R, Lantis JC 2nd, Beavers FP, Kent KC. Tibial angioplasty as an alternative strategy in patients with limb-threatening ischemia. Ann Vasc Surg. 2005 Jan;19(1):63-8. doi: 10.1007/s10016-004-0136-0.

Reference Type: BACKGROUND

PMID: 15714369 (View on PubMed)

Other Identifiers

2012-001825-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2012-T2DM-CLI

Identifier Type: -

Identifier Source: org_study_id