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

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ClinicalTrials.gov Identifier: NCT02454231
Recruitment Status : Completed
First Posted : May 27, 2015
Last Update Posted : May 9, 2017
Sponsor:
Collaborator:
Tuscany Region
Information provided by (Responsible Party):
Enrico Maggi, University of Florence

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).

Condition or disease Intervention/treatment Phase
Critical Limb Ischemia Biological: Transplantation of circulating CD14+CD34+cells Biological: Transplantation of BM MNC Phase 2 Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Monocentric Randomized Study for the Therapy of Critic Limb Ischemia With Bone Marrow- or Peripheral Blood-derived Stem Cells
Study Start Date : September 2009
Actual Primary Completion Date : May 2015
Actual Study Completion Date : October 2015

Arm Intervention/treatment
Experimental: peripheral blood EPC injection Biological: Transplantation of circulating CD14+CD34+cells
intramuscular injection of circulating EPC at leg level

Active Comparator: bone marrow MNC injection Biological: Transplantation of BM MNC
intramuscular injection of BM MNC at leg level




Primary Outcome Measures :
  1. Safety as measured by evaluation of any adverse event temporary correlated with the treatment [ Time Frame: 52 weeks of follow-up ]
    Evaluation of any adverse event temporary correlated with the treatment

  2. Changes in ischemic leg perfusion from baseline [ Time Frame: 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 Outcome Measures :
  1. Improvement of Mean values of the transcutaneous partial oxygen pressure (TCP02) [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Improvement of mean values of the transcutaneous partial oxygen pressure of at least 20%

  2. Improvement of mean values of ankle brachial pressure index (ABI) [ Time Frame: 4, 22, 52 weeks of follow-up ]
    improvement (at least 25% increase) of Mean values of ankle brachial pressure index

  3. Improvement of vessel anatomical status [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Improvement of leg vascularization as assessed by color Doppler ultrasound

  4. Improvement of leg perfusion [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Improvement of leg perfusion as assessed by plethysmography characterization

  5. Improvement of vessel anatomical status [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Improvement of leg vascularization as assessed by Angio-CT, defined as presence of new vessels

  6. Quality of life Improvement [ Time Frame: -28, 0, 28 weeks of follow-up ]
    Quality of life, as assessed by the disease-specific ST22 and SF36 questionaries

  7. improvement of rest pain [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Rest pain as evaluated by visual analogue pain scale (VAS)

  8. Improvement of trophic limb lesions [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Mean score of trophic limb lesions, as evaluated according to Wagner international grade

  9. Reduction of numbers of major amputation (amputation free survival ) [ Time Frame: 4, 22, 52 weeks of follow-up ]
    Reduction of numbers of major amputation compared with untreated patients

  10. improvement of microvascular anatomy [ Time Frame: 4, 22, 52 weeks of follow-up ]
    evaluation of microvascular anatomy as assessed by capillaroscopy



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • Exclusion criteria were: age < 40;
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02454231


Locations
Italy
Azienda Ospedaliero-Universitaria Careggi
Florence, Tuscany, Italy, 50134
Sponsors and Collaborators
University of Florence
Tuscany Region
Investigators
Principal Investigator: Enrico Maggi, professor University of Florence

Publications:

Responsible Party: Enrico Maggi, Professor, MD, Director of the Unit of Immunology and Cellular Therapy, University of Florence
ClinicalTrials.gov Identifier: NCT02454231     History of Changes
Other Study ID Numbers: UFlorence
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017

Keywords provided by Enrico Maggi, University of Florence:
EPC
CD34+
CD14+CD34low

Additional relevant MeSH terms:
Ischemia
Pathologic Processes