Critical Limb Ischemia
Conditions
Keywords
EPC, CD34+, CD14+CD34low
Brief summary
The investigators designed a randomized clinical trial (stem cell emergency life threatening arteriopathy or SCELTA) to compare the therapeutic efficacy of the auto-transplant of enriched circulating EPCs (ECEPCs) with auto-transplant of BM-MNCs. ECEPCs, obtained by immunoselection of CD14+ and CD34+ cells, or BM-MNCs, were injected intramuscularly in the affected limb of patients with critical limb ischemia (CLI).
Detailed description
Peripheral arterial disease comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI), which is a very invalidating condition characterized by rest pain, march inability, trophic lesions and unavoidable progression to major amputations, which are burdened by a high mortality in the first year. The pathophysiology of CLI often associates with a defect in the development of collateral vessels and angiogenesis, a process which refers to the formation of new blood vessels into tissue, due to circulating endothelial progenitor cells (EPCs) and vascular progenitor cells. In the last few years, significant improvement of this condition has been reported following bone marrow (BM) autotransplant or autotransplant of peripheral EPCs mobilized from BM through the injection of granulocyte-colony stimulatory factor (G-CSF). In a previous study, the investigators found that individually variable proportions of circulating CD14+ cells expressed low levels of CD34 (CD14+CD34low) and revealed the functional phenotype of EPCs. The investigators therefore designed a monocentric randomized clinical trial to compare the therapeutic efficacy of BM autotransplant with the autotransplant of a population of circulating CD34+ and CD14+CD34low enriched by a closed sterile immunomagnetic system (enriched circulating EPCs or ECEPCs), without a previous EPC mobilization from BM. Patients will be evaluated for clinical parameters and ABI, TBI, TCp02 before autotransplant and at three follow-up times after the autotransplant (4, 24 and 52 weeks); also angio-TAC of legs, capillaroscopy, and photoplethysmography will be evaluated at 4, and even at 52 weeks.
Interventions
BIOLOGICALTransplantation of circulating CD14+CD34+cells
intramuscular injection of circulating EPC at leg level
BIOLOGICALTransplantation of BM MNC
intramuscular injection of BM MNC at leg level
Sponsors
Tuscany Region
University of Florence
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eligible patients were men and women aged more than 40 years with a diagnosis of CLI due to atherosclerosis of the lower extremities, as defined by the presence of persistent rest pain requiring systemic and continued analgesic treatment in the last 15 days and/or the presence of trophic lesions imputable to the occluding arteriopathy, an ankle-brachial Index (ABI) \< 0.40 (with systolic ankle pressure \< 50-70 Hg mm), a toe/brachial index (TBI) \< 0.40 (with big toe systolic pressure \< 30-50 Hg mm), and a transcutaneous oxygen pressure (TC pO2) \< 30 Hg mm. * The patient was considered as eligible for the treatment and enrolled only after the demonstration that intravascular or surgical re-vascularization was not possible, as revealed by ecography and angio-CAT, or when the patient refused to undergo surgical treatments and after having obtained his/her written informed consensus.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as measured by evaluation of any adverse event temporary correlated with the treatment | 52 weeks of follow-up | Evaluation of any adverse event temporary correlated with the treatment |
| Changes in ischemic leg perfusion from baseline | 4, 22, 52 weeks of follow-up | Improvement of leg perfusion as assessed by values of Time to Pick (TTP) evaluated by ultrasound tools |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of vessel anatomical status | 4, 22, 52 weeks of follow-up | Improvement of leg vascularization as assessed by color Doppler ultrasound |
| Improvement of leg perfusion | 4, 22, 52 weeks of follow-up | Improvement of leg perfusion as assessed by plethysmography characterization |
| Quality of life Improvement | -28, 0, 28 weeks of follow-up | Quality of life, as assessed by the disease-specific ST22 and SF36 questionaries |
| Improvement of Mean values of the transcutaneous partial oxygen pressure (TCP02) | 4, 22, 52 weeks of follow-up | Improvement of mean values of the transcutaneous partial oxygen pressure of at least 20% |
| Reduction of numbers of major amputation (amputation free survival ) | 4, 22, 52 weeks of follow-up | Reduction of numbers of major amputation compared with untreated patients |
| Improvement of trophic limb lesions | 4, 22, 52 weeks of follow-up | Mean score of trophic limb lesions, as evaluated according to Wagner international grade |
| improvement of microvascular anatomy | 4, 22, 52 weeks of follow-up | evaluation of microvascular anatomy as assessed by capillaroscopy |
| improvement of rest pain | 4, 22, 52 weeks of follow-up | Rest pain as evaluated by visual analogue pain scale (VAS) |
| Improvement of mean values of ankle brachial pressure index (ABI) | 4, 22, 52 weeks of follow-up | improvement (at least 25% increase) of Mean values of ankle brachial pressure index |
Countries
Italy
Outcome results
None listed