Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization

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:

Inclusion criteria

• Type 1 or 2 diabetes mellitus
• Grade II-III Rutherford-Becker peripheral vascular disease affecting at least one limb
• Arterial obstruction(s) located at infrapopliteal level
• No options of endoarterial or surgical revascularization
• Life expectancy more than 2 years
• Unlikelihood of major amputation of the leg during the next 12 months
• Normal analytical parameters in blood: leucocytes>3000/micoL, neutrophils>1500 microL, Hb>10mg/dl, platelets>100000 microL,AST and ALT<2.5 standard value, creatinin<2.5 mg/dl
• Written informed consent
• Negative pregnancy test when applicable

Exclusion criteria

• History of neoplasm or hematological disease
• Uncontrolled high blood pressure (>180/110)
• Severe cardiac insufficiency (NYHA IV) or ejection fraction<30%
• Malignant ventricular arrythmia
• Deep venous thrombosis during the last 3 months
• Active bacterial infection
• Treatment with hyperbaric oxygen, vasoactive drugs, Cox-II inhibitors or antiangiogenic agents
• Body mass index > 40
• Alcoholism
• Proliferative retinopathy
• HIV, HBV or HCV viral infection
• Stroke or myocardial infarction during the last 3 months