Monocentric Trial: Stem Cell Emergency Life Threatening Limbs Arteriopathy (SCELTA)

NCT ID: NCT02454231

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2015-10-31

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.

Conditions

Critical Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

peripheral blood EPC injection

Group Type: EXPERIMENTAL

Transplantation of circulating CD14+CD34+cells

Intervention Type: BIOLOGICAL

intramuscular injection of circulating EPC at leg level

bone marrow MNC injection

Group Type: ACTIVE_COMPARATOR

Transplantation of BM MNC

Intervention Type: BIOLOGICAL

intramuscular injection of BM MNC at leg level

Interventions

Transplantation of circulating CD14+CD34+cells

intramuscular injection of circulating EPC at leg level

Intervention Type: BIOLOGICAL

Transplantation of BM MNC

intramuscular injection of BM MNC at leg level

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• not atherosclerotic CLI,
• myocardial infarction occurrence in the 6 months;
• cardiac failure of III-IV class NYHA;
• ejection fraction lower than 40%;
• arterial hypertension (>160/100 Hg mm) uncontrolled despite the usage of two anti-hypertensive drugs;
• presence of current or chronic severe infectious diseases;
• osteomyelitis;
• diabetes with glycate hemoglobin > 7.5;
• proliferative diabetic retinopathy;
• hemorrhagic disorders;
• non-atherosclerotic arteriopathy;
• chronic airway insufficiency (p02 <65 Hg mm, pCO2 > 0.50 Hg mm);
• renal failure (creatinine > 2mg/dl);
• contraindications or intolerance to contrast media for radiologic imaging

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tuscany Region

UNKNOWN

Sponsor Role: collaborator

University of Florence

OTHER

Sponsor Role: lead

Responsible Party

Enrico Maggi

Professor, MD, Director of the Unit of Immunology and Cellular Therapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Enrico Maggi, professor

Role: PRINCIPAL_INVESTIGATOR

University of Florence

Locations

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, Italy

Countries

Italy

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Other Identifiers

UFlorence

Identifier Type: -

Identifier Source: org_study_id