Critical Limb Ischemia (CLI)
Conditions
Brief summary
To study the effect of the stem cells therapy autologous mononuclear from the bone marrow, autologous progenitor endothelial CD133 cells from the bone marrow and autologous mesenchymal stem cells from adipose tissue on the inflammatory cytokines, the resistance to insulin and the decrease of the needs of insulin, besides evaluates the safety, viability and efficiency of the intra-arterial infusion of stem cells in diabetic patients type 2 with CLI.
Detailed description
To study the effect of the stem cells therapy autologous mononuclear from the bone marrow, autologous progenitor endothelial CD133 cells from the bone marrow and autologous mesenchymal stem cells from adipose tissue on the inflammatory cytokines, the resistance to insulin and the decrease of the needs of insulin, besides evaluates the safety, viability and efficiency of the intra-arterial infusion of stem cells in diabetic patients type 2. Diabetic patients will include with critical ischemia chronicle of at least a low member limb (CLI) and without possibilities of revascularization. 48 evaluable patients will be included, of which 36 patients will be included in the experimental group (12 for every cellular group) and 12 in the group control by conventional treatment. The population to studying will be constituted by 48 evaluable patients.
Interventions
DRUGStem cell infusion
Unique stem cell infusion of the randomized group
Sponsors
Iniciativa Andaluza en Terapias Avanzadas
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 and ≤ 85 years 2. Diabetic type 2, in treatment with insulin at least 3 previous months. 3. Vascular disease infrapopliteal atherosclerotic of severe degree (Patients with category Rutherford-Becker ≥ 4), pretty or bilateral. The critical ischemia of the foot is defined as a persistent / persistent pain that needs analgesia and / or not healing present sores\> 4 weeks, without evidence of improvement with conventional therapies and / or walking test between 1-6 minutes in two ergometries separated at least for 2 weeks and / or index ankle - arm in rest \<0,8. 4. Impossibility of revascularization surgical or endovascular or I fail in the surgery of revascularization performed at least 30 days before, with persistence or entry in phase of critical ischemia 5. Life expectancy \> 2 years. 6. Major amputation is not foreseen in any of the members in the next 6 months after the incorporation. 7. Normal Biochemical and bone marrow parameters defined for: * Leukocytes ≥ 3000 * Neutrophils ≥ 1500 * Platelets ≥ 140000 * AST/ALT ≤ 2,5 standard range institution * Creatinine ≤2,5 mg/dl and explanation of creatinine ≤ 30 ml/min (MDRD4) 8. The women in fertile age will have to obtain negative results in a pregnancy test realized in the moment of the incorporation in the study and promise to use a contraceptive method medically approved while the study lasts. 9. Patients who give his Informed Consent in writing for the participation in the study. 10. Patients who have not taken part in another clinical trial in the last 3 months before the incorporation.
Exclusion criteria
1. Precedent of neoplasia or hematologic disease (disease myeloproliferative, syndrome myelodysplasic or leukaemia) in the last 2 years. 2. Major previous amputation. 3. Patients with arterial uncontrolled hypertension (defined as arterial tension\> 180/110 in more than one occasion). 4. Cardiac severe insufficiency (NYHA the IVth) or Fraction of Ejection of left ventricle (FAITH) lower than 30 %. 5. Patients with ventricular malignant arrhythmias or unstable angina. 6. Diagnosis of venous deep thrombosis in 3 previous months. 7. Patients with genotype DD of the ECA or genotype E4 of the apo E. 8. Concomitant therapy that includes oxygen hyperbaric, vasoactive substances, agents against angiogenesis or inhibiting Cox-II. The agents use is allowed antiplatelets. 9. Index of corporal mass\> 40 Kg/m2. 10. Patients with the diagnosis of alcoholism in the moment of the incorporation. 11. Proliferative Retinopathy without possibility of treatment. 12. Diabetic Nephropathy with haemodialysis 13. Concomitant disease that reduces the life expectancy to less than 1 years. 14. Impossibility foreseen to obtain the inhaled one of 100ml of bone marrow. 15. Infection for HIV, Hepatitis B or Hepatitis C. 16. Impede in the follow-up. 17. ACV or heart attack of myocardium in the last 3 months 18. Anaemia (Haemoglobin \<7.9 g/dl) 19. Patients before treated with cellular therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | the entire follow-up period, in the first 24 hours after the infusion of stem cells | To evaluate the possible complications derived from the procedure (in the first 24 hours after the infusion of stem cells and the incident of Serious Adverse Events and not Serious Adverse Events related to the IMPD or to the procedure of administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy measured by: The changes in the requirements of insulin, Peptide C, Resistance to the insulin, inflammatory Cytokines, pancreatic Reservation, Quantification of the degree of neovascularization (angio/arteriogenesis and vasculogenesis) | 6 months | Efficacy measured by: The changes in the requirements of insulin, Peptide C, Resistance to the insulin, inflammatory Cytokines, pancreatic Reservation, Quantification of the degree of neovascularization (angio/arteriogenesis and vasculogenesis) after 6 months of the stem cells infusion |
Countries
Spain
Outcome results
None listed