Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia

Study Overview
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Brief Summary
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Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3 clinical trial of 3 parallel groups.

Detailed Description
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Disease or disorder under study: Critical ischemia of the lower limbs in diabetic patients without the possibility of revascularization. Main valuation variable: Proportion of Adverse Events related to treatment.

Official Title
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Multicenter, Randomized, Dose-search, Parallel, Double-blind, and Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Intramuscular Administration of Allogeneic Adipose Tissue Adult Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia Without Possibility of Revascularization

Conditions
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Limb Ischemia, Diabetic Foot

Intervention / Treatment
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* Drug: High dose allogeneic mesenchymal stromal cells
* Drug: Low dose allogeneic mesenchymal stromal cells
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet ALL of the following criteria to be included in the study: Patients of both sexes. Age between 40 and 90 years. Severe grade vascular arteriosclerosis (category RB 4 and 5 mono or bilateral). Impossibility of surgical or endovascular revascularization or failure in revascularization surgery performed, at least 30 days before inclusion in the study, defining failure as direct non-arrival of vessels to the plantar arch. Normal biochemical parameters defined by: Leukocytes> 3000 / mm3 Neutrophils> 1500 / mm3 Platelets> 100,000 / mm3 AST / ALT <2.5x upper limit of normal In patients with an ischemic ulcer, it must be stable for at least 1 week. Patients under conventional medical treatment for CLI. Women of childbearing age must obtain a negative result in a urine pregnancy test performed at the time of inclusion in the study and commit to using an effective contraceptive method during their participation in the study. Patients who have not participated in any other clinical trial during the 3 months prior to the inclusion visit. Patients who sign the informed consent. Exclusion Criteria: Patients who present SOME of the following criteria may not be selected to participate in this study: CLI with tissue loss in the target member (category 6 of RB). Previous major amputation in the target member. Uncontrolled hypertension (defined as PAS> 180 or PAD> 110 in at least 2 determinations during the selection period). Patients with severe heart failure or ejection fraction less than 30%. Patients with a previous diagnosis of ventricular arrhythmias or unstable angina. Patients with septicemia. Patients diagnosed with deep vein thrombosis in the 3 months prior to their inclusion in the study. Concomitant therapy that includes hyperbaric oxygen, angiogenic agents or Cox II inhibitors. Contraindication to perfusion NMR. Proliferative retinopathy without treatment. Diabetic nephropathy in hemodialysis. Patients previously treated with cell therapy, gene therapy or growth factors in the last year. Concomitant disease that limits life expectancy to 1 year or that does not ensure the follow-up period. Patients who have suffered a stroke or myocardial infarction in the 3 months prior to the inclusion visit. Severe anemia (hemoglobin <7.9g / dl) in the inclusion analysis. Patients with a previous diagnosis of chronic alcoholism. Any clinically significant anomaly detected in the Selection Period and which, in the opinion of the investigator, constitutes an impediment to the correct participation of the patient in the study or the fulfillment of the procedures established therein.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control arm<br>0.9% physiological saline | Drug: Placebos<br>* 0,9% physiological saline<br>|
| Experimental: Low dose treatment arm<br>Low dose allogeneic mesenchymal stem cells derived from adipose tissue | Drug: Low dose allogeneic mesenchymal stromal cells<br>* Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly<br>|
| Experimental: High dose treatment arm<br>High dose allogeneic mesenchymal stem cells derived from adipose tissue | Drug: High dose allogeneic mesenchymal stromal cells<br>* Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complication rate after treatment administration |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of vascularization though RMN |  | 1 year | 
| Rutherford-Becker scale |  | 1 year | 
| Wifi scale |  | 1 year | 
| Ankle arm index |  | 1 year | 
| Temperature | (ºC) | 1 year | 
| Twin perimeter | (cm) | 1 year | 
| Neuropathic symptoms (altered sensitivity) |  | 1 year | 
| % amputations |  | 1 year |