Clinical trial NCT01818310: Safety and Efficacy Study of Autologous Bone Marrow Aspirate Concentrate for No-Option Critical Limb Ischemia
Official title: Randomised Clinical Study of Safety and Efficacy of Autologous Bone Marrow Aspirate Concentrate (BMAC) for No-option_critical Limb Ischemia in Type-II Diabetes Mellitus Patients. (DIALEG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Critical Lower Limb Ischemia
Type-2 Diabetes Mellitus
Keywords: ischemia
diabetes mellitus
bone marrow aspirate concentrate (BMAC)
Lead sponsor: University Hospital Ostrava
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Czech Republic
name: Regional Council of the Moravian-Silesian region, KU MSK
First posted: 2013-03-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Amputation-free survival
timeFrame: 18 months
Secondary outcomes:
measure: Tissue perfusion parameters
timeFrame: 4 years
measure: Clinical outcome classification
timeFrame: 4 years
measure: Functional angiogenesis imaging outcome
timeFrame: 4 years
measure: Quality of life outcome
timeFrame: 4 years
Other outcomes:
measure: Changes in lymphocyte subsets and levels of inflammatory and antiinflammatory cytokines in each of the groups.
timeFrame: 24 months
measure: Metabolic response
timeFrame: 24 months
measure: Blood glucose and pancreatic function response
timeFrame: 24 months
Locations:
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
Study officials:
affiliation: University Hospital Ostrava
name: Vaclav Prochazka, MD, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.