Clinical trial NCT04466007: Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Limb Ischemia
Diabetic Foot
Lead sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Sponsor class: OTHER
Collaborators: name: Clinica Universidad de Navarra, Universidad de Navarra
name: Hospital Universitario La Paz
name: Gregorio Marañón Hospital
name: Hospital Clínico Universitario de Valladolid
name: Hospital Universitario Virgen de la Arrixaca
name: University of Salamanca
name: Hospital General Universitario de Alicante
name: Hospital Universitario La Fe
name: Hospital Victoria Eugenia Cruz Roja Española
First posted: 2020-07-10
Enrollment: 90
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complication rate after treatment administration
timeFrame: 1 year
Secondary outcomes:
measure: Evaluation of vascularization though RMN
timeFrame: 1 year
measure: Rutherford-Becker scale
timeFrame: 1 year
measure: Wifi scale
timeFrame: 1 year
measure: Ankle arm index
timeFrame: 1 year
measure: Temperature
timeFrame: 1 year
measure: Twin perimeter
timeFrame: 1 year
measure: Neuropathic symptoms (altered sensitivity)
timeFrame: 1 year
measure: % amputations
timeFrame: 1 year
Other outcomes:
measure: SF-12 questionnaire
timeFrame: 1 year
measure: VascuQol-6 questionnaire
timeFrame: 1 year
Locations:
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: La Paz University Hospital
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Victoria Eugenia Cruz Roja Española
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital de Valladolid
Study officials:
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