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

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Status and phase: Completed; Phase 2

Conditions: Diabetic Foot; Limb Ischemia

Treatments: Drug: High dose allogeneic mesenchymal stromal cells; Drug: Placebos; Drug: Low dose allogeneic mesenchymal stromal cells

Study type: Interventional

Funder types: Other

Identifiers

NCT04466007

NOMA (No More Amputations)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 90 patients

Sex: All

Ages: 40 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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90 participants in 3 patient groups, including a placebo group

Control arm

Placebo Comparator group

Description:

0.9% physiological saline

Treatment:

Drug: Placebos

Low dose treatment arm

Experimental group

Description:

Low dose allogeneic mesenchymal stem cells derived from adipose tissue

Treatment:

Drug: Low dose allogeneic mesenchymal stromal cells

High dose treatment arm

Experimental group

Description:

High dose allogeneic mesenchymal stem cells derived from adipose tissue

Treatment:

Drug: High dose allogeneic mesenchymal stromal cells