Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization
Condition: Critical Limb Ischemia (CLI); Diabetic Foot
MeSH terms: Diabetic Foot; Chronic Limb-Threatening Ischemia; Ischemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The aim of the study is to evaluate the safety and feasibility of autologous bone marrow
      mononuclear cells autologous administered intra-arterially in the affected limb of diabetic
      patients with chronic critical ischemia of the lower limbs (CLI) without possibility of
      revascularization or other therapeutic alternatives.

      The trial hypothesis we propose consists of mononuclear cells of bone marrow providing
      progenitor cells with regenerative capacity and secrete also several angiogenic factors, and
      their implantation into ischemic tissues with both elements should contribute to angiogenesis
      and tissue regeneration with recovery of the circulation in the affected limb
    

Detailed description: 
      Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group
      controlled with three dose levels.

      The study population will consist of a total of 60 diabetic patients with chronic critical
      ischemia of one leg (CLI) and no possibility of revascularization. In the experimental group
      will include a total of 45 patients divided into three dose levels, 15 patients in each level
      (increasing doses of mononuclear cells of bone marrow evenly) and 15 patients in control
      group (no cell therapy). Patients will be randomly assigned to either the control group or to
      any of the three experimental groups in which the dose of mononuclear cells of bone marrowo
      will be:

        -  Group 1(15 patients): no cell therapy.

        -  Group 2(15 patients): 1x108 mononuclear cells of bone marrow

        -  Gropu 3(15 patients): 5x108 mononuclear cells of bone marrow

        -  Group 4(15 patients): 1x109 mononuclear cells of bone marrow The cell therapy medicinal
           product shall be administered in all cases intraarterially.

      Patients were evaluated by clinical, radiological and angiologist methods. This is a
      randomized controlled trial in which the safety and feasibility of cell therapy medicinal
      product shall be measured by comparing the response variables after treatment compared to
      baseline prior to implementation. Secondarily the results obtained are compared with each of
      the dose groups.

      Patients will receive in a concomitant way the drug treatment established by the good
      practice, so it would certainly be possible that some improvement occurs due to drug
      treatment.

      The primary variable is the improvement in the vascularización of the treated limb determined
      by clinical, angiologic and angiographic parameters.

      It is estimated that the inclusion period lasts between twelve and eighteen months with
      twelve months follow-up. Therefore the total study duration range between twenty-four and
      thirty months from the inclusion of the first patient to the end of the follow-up of the last
      patient included.

      Objectives of the study:

      - Main objective: To evaluate the safety and feasibility of mononuclear cells of autologous
      bone marrow administered intra-arterially in the affected limb of diabetic patients with
      chronic critical ischemia of the lower limbs without possibility of revascularization or
      other therapeutic alternatives.

      Secondary objectives:
    

Intervention name(s): Intraarterial infusion of autologous bone marrow cells
Intervention type(s): Other
Intervention description(s): Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: critical limb ischemia (CLI); diabetic foot; bone marrow derived mononuclear cells; cell therapy