<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04466007</url>
  </required_header>
  <id_info>
    <org_study_id>NOMA (No More Amputations)</org_study_id>
    <nct_id>NCT04466007</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinica Universidad de Navarra, Universidad de Navarra</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario La Paz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gregorio Marañón Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Clínico Universitario de Valladolid</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario Virgen de la Arrixaca</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Salamanca</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital General Universitario de Alicante</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario La Fe</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Victoria Eugenia Cruz Roja Española</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3&#xD;
      clinical trial of 3 parallel groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Disease or disorder under study: Critical ischemia of the lower limbs in diabetic patients&#xD;
      without the possibility of revascularization.&#xD;
&#xD;
      Main valuation variable: Proportion of Adverse Events related to treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 11, 2021</start_date>
  <completion_date type="Anticipated">April 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complication rate after treatment administration</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of vascularization though RMN</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rutherford-Becker scale</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wifi scale</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ankle arm index</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temperature</measure>
    <time_frame>1 year</time_frame>
    <description>(ºC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Twin perimeter</measure>
    <time_frame>1 year</time_frame>
    <description>(cm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic symptoms (altered sensitivity)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% amputations</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>SF-12 questionnaire</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>VascuQol-6 questionnaire</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Limb Ischemia</condition>
  <condition>Diabetic Foot</condition>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% physiological saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low dose treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose allogeneic mesenchymal stem cells derived from adipose tissue</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose allogeneic mesenchymal stem cells derived from adipose tissue</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose allogeneic mesenchymal stromal cells</intervention_name>
    <description>Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly</description>
    <arm_group_label>High dose treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose allogeneic mesenchymal stromal cells</intervention_name>
    <description>Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly</description>
    <arm_group_label>Low dose treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>0,9% physiological saline</description>
    <arm_group_label>Control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet ALL of the following criteria to be included in the study:&#xD;
&#xD;
          -  Patients of both sexes.&#xD;
&#xD;
          -  Age between 40 and 90 years.&#xD;
&#xD;
          -  Severe grade vascular arteriosclerosis (category RB 4 and 5 mono or bilateral).&#xD;
&#xD;
          -  Impossibility of surgical or endovascular revascularization or failure in&#xD;
             revascularization surgery performed, at least 30 days before inclusion in the study,&#xD;
             defining failure as direct non-arrival of vessels to the plantar arch.&#xD;
&#xD;
          -  Normal biochemical parameters defined by:&#xD;
&#xD;
               -  Leukocytes&gt; 3000 / mm3&#xD;
&#xD;
               -  Neutrophils&gt; 1500 / mm3&#xD;
&#xD;
               -  Platelets&gt; 100,000 / mm3&#xD;
&#xD;
               -  AST / ALT &lt;2.5x upper limit of normal&#xD;
&#xD;
          -  In patients with an ischemic ulcer, it must be stable for at least 1 week.&#xD;
&#xD;
          -  Patients under conventional medical treatment for CLI.&#xD;
&#xD;
          -  Women of childbearing age must obtain a negative result in a urine pregnancy test&#xD;
             performed at the time of inclusion in the study and commit to using an effective&#xD;
             contraceptive method during their participation in the study.&#xD;
&#xD;
          -  Patients who have not participated in any other clinical trial during the 3 months&#xD;
             prior to the inclusion visit.&#xD;
&#xD;
          -  Patients who sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who present SOME of the following criteria may not be selected to participate in&#xD;
        this study:&#xD;
&#xD;
          -  CLI with tissue loss in the target member (category 6 of RB).&#xD;
&#xD;
          -  Previous major amputation in the target member.&#xD;
&#xD;
          -  Uncontrolled hypertension (defined as PAS&gt; 180 or PAD&gt; 110 in at least 2&#xD;
             determinations during the selection period).&#xD;
&#xD;
          -  Patients with severe heart failure or ejection fraction less than 30%.&#xD;
&#xD;
          -  Patients with a previous diagnosis of ventricular arrhythmias or unstable angina.&#xD;
&#xD;
          -  Patients with septicemia.&#xD;
&#xD;
          -  Patients diagnosed with deep vein thrombosis in the 3 months prior to their inclusion&#xD;
             in the study.&#xD;
&#xD;
          -  Concomitant therapy that includes hyperbaric oxygen, angiogenic agents or Cox II&#xD;
             inhibitors.&#xD;
&#xD;
          -  Contraindication to perfusion NMR.&#xD;
&#xD;
          -  Proliferative retinopathy without treatment.&#xD;
&#xD;
          -  Diabetic nephropathy in hemodialysis.&#xD;
&#xD;
          -  Patients previously treated with cell therapy, gene therapy or growth factors in the&#xD;
             last year.&#xD;
&#xD;
          -  Concomitant disease that limits life expectancy to 1 year or that does not ensure the&#xD;
             follow-up period.&#xD;
&#xD;
          -  Patients who have suffered a stroke or myocardial infarction in the 3 months prior to&#xD;
             the inclusion visit.&#xD;
&#xD;
          -  Severe anemia (hemoglobin &lt;7.9g / dl) in the inclusion analysis.&#xD;
&#xD;
          -  Patients with a previous diagnosis of chronic alcoholism.&#xD;
&#xD;
          -  Any clinically significant anomaly detected in the Selection Period and which, in the&#xD;
             opinion of the investigator, constitutes an impediment to the correct participation of&#xD;
             the patient in the study or the fulfillment of the procedures established therein.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital General de Alicante</name>
      <address>
        <city>Alicante</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>La Paz University Hospital</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Victoria Eugenia Cruz Roja Española</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Valladolid</name>
      <address>
        <city>Valladolid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
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  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Foot</mesh_term>
    <mesh_term>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04466007
org study id: NOMA (No More Amputations)
nct id: NCT04466007
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3
      clinical trial of 3 parallel groups.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Complication rate after treatment administration
time frame: 1 year
measure: Evaluation of vascularization though RMN
time frame: 1 year
measure: Rutherford-Becker scale
time frame: 1 year
measure: Wifi scale
time frame: 1 year
measure: Ankle arm index
time frame: 1 year
measure: Temperature
time frame: 1 year
description: (ºC)
measure: Twin perimeter
time frame: 1 year
description: (cm)
measure: Neuropathic symptoms (altered sensitivity)
time frame: 1 year
measure: % amputations
time frame: 1 year
measure: SF-12 questionnaire
time frame: 1 year
measure: VascuQol-6 questionnaire
time frame: 1 year
arm group label: Control arm
arm group type: Placebo Comparator
description: 0.9% physiological saline
arm group label: Low dose treatment arm
arm group type: Experimental
description: Low dose allogeneic mesenchymal stem cells derived from adipose tissue
arm group label: High dose treatment arm
arm group type: Experimental
description: High dose allogeneic mesenchymal stem cells derived from adipose tissue
intervention type: Drug
intervention name: High dose allogeneic mesenchymal stromal cells
description: Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly
arm group label: High dose treatment arm
intervention type: Drug
intervention name: Low dose allogeneic mesenchymal stromal cells
description: Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly
arm group label: Low dose treatment arm
intervention type: Drug
intervention name: Placebos
description: 0,9% physiological saline
arm group label: Control arm
criteria: 
gender: All
minimum age: 40 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
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responsible party type: Sponsor
mesh term: Diabetic Foot
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Ischemia
sharing ipd: Undecided