Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Limb Ischemia (CLI).
Condition: Critical Limb Ischemia (CLI)
MeSH terms: Chronic Limb-Threatening Ischemia; Ischemia
Study type: Interventional
Phase: Phase 2

Summary: 
      Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group
      controlled with three levels of dose.

      The hypothesis of the test we propose is that the mononuclear cells of bone marrow provide
      progenitor cells with regenerative capacity and besides secrete 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: 
      The study population will consist of a total of 44 non-diabetic patients with chronic
      critical ischemia in at least one of their lower limbs (CLI) and without possibility of
      revascularization. In the experimental group will be included a total of 33 patients divided
      into three levels of dose, 11 patients in each level (increasing dose of mononuclear cells
      from autologous bone marrow) and other 11 patients in control group.

        -  11 patients in group 1 will not receive cell therapy, and they will only receive
           conventional treatment, acting as a control group.

        -  11 patients in group 2 will receive 1x108 autologous bone marrow mononuclear cells.

        -  11 patients in group 3 will receive 5x108 autologous bone marrow mononuclear cells.

        -  11 patients in group 4 will receive 1x109 autologous bone marrow mononuclear cells.

      The cell therapy drug will be administered intra-arterially in all cases. Patients will be
      evaluated by clinical, radiological and angiological methods (ankle / brachial pressure
      index, transcutaneous oxygen pressure, perimeter calf muscle, presence of ulcers, oximetry
      and digital arteriography).

      Patients will receive concomitant drug treatment established by the good clinical practice,
      so undoubtedly it could be possible that some improvement occurs due to drug treatment.

      It is estimated that the inclusion period is approximately 42 months, and the follow-up of
      each patient of six months. Therefore the total duration of the study will be about forty
      eight months from the entry of the first patient to the end of the follow-up period of the
      last patient included.

      The primary variable is the improvement in the vascularisation of the treated limb determined
      by clinical, angiographic and angiologist parameters.

      Study objectives :

      • Main objective: To evaluate the safety and feasibility of the autotransplantation of
      autologous bone marrow mononuclear cells administered intra-arterially in non-diabetic
      patients with critical chronic ischemia of the lower limbs without possibility of either
      revascularization or other therapeutic alternatives.

      Secondary objectives:

        1. To compare the effect of three increasing dose of mononuclear cells from autologous bone
           marrow in the recovery of clinical, angiographic angiologist parameters in non-diabetic
           patients with critical chronic ischemia of lower limbs to a control group that will have
           been applied to a conventional treatment.

        2. To analyze complications from regenerative therapy itself, from the route of
           administration and / or study procedures.
    

Intervention name(s): Intraarterial Infusion of Autologous Bone Marrow Mononuclear 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 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Critical Limb Ischemia (CLI); Cell Therapy; Bone marrow mononuclear cells