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

Phase 2

Completed

• Conditions: Critical Lower Limb Ischemia; Type-2 Diabetes Mellitus

• Registration Number: NCT01818310
• Lead Sponsor: University Hospital Ostrava

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.

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-09-27
• Study First Submitted QC: 2013-03-21
• Study First Posted: 2013-03-26
• Primary Completion: 2018-09
• Study Completion: 2018-10
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-29
• Last Update Posted: 2021-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Amputation-free survival	18 months	The data for Primary outcome will be collected throughout the first 18 months of the study. The assessed parameters will include amputation-free survival in order to verify the safety and efficacy of the treatment.

Secondary Outcome Measures

Name	Time	Method
Functional angiogenesis imaging outcome	4 years	The efficacy of BMAC application will be evaluated throughout the whole course of the clinical trial, with final assessment at the end of the trial.; - Increase of the number and quality of newly created vessels measured according to digital subtraction angiography (DSA) or MR-angiography (in allergic patients)
Quality of life outcome	4 years	The efficacy of BMAC application will be evaluated throughout the whole course of the clinical trial, with final assessment at the end of the trial.; * Measurable decrease of pain measured on the scale and QOL questionnaire (RAND-36).; * Healing of the defect or gangrene (size and state of the wound)
Clinical outcome classification	4 years	The efficacy of BMAC application will be evaluated throughout the whole course of the clinical trial, with final assessment at the end of the trial.; - Improvement of the Rutherford scale of CLI
Tissue perfusion parameters	4 years	The efficacy of BMAC application will be evaluated throughout the whole course of the clinical trial, with final assessment at the end of the trial.; * Increase of the monitored parameters of the tissue perfusion measured with LDP-Periflux 5000 (Perimed), i.e. increase of the ABI - ankle-brachial index, TP - toe pressure, TBI- Toe Brachial index and TcpO2- transcutaneous oxygen pressure.; * Decrease of the SPP perfusion parameter - skin perfusion pressure reflecting an inflammatory activity of the affected limb.

Trial Locations

Locations (1)

University Hospital Ostrava; 🇨🇿 Ostrava, Czechia