<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/NCT03239535</url>
  </required_header>
  <id_info>
    <org_study_id>MSC-CLI/FMBA/001</org_study_id>
    <nct_id>NCT03239535</nct_id>
  </id_info>
  <brief_title>Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy</brief_title>
  <official_title>Allogeneic Mesenchymal Stem Cells for the Critical Limb Ischemia Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal Research Clinical Center of Federal Medical &amp; Biological Agency, Russia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal Research Clinical Center of Federal Medical &amp; Biological Agency, Russia</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>
      The clinical trial aims to study the safety and efficacy of adult allogeneic mesenchymal stem&#xD;
      cells for the treatment of critical limb ischemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2013</start_date>
  <completion_date type="Anticipated">November 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>24 months</time_frame>
    <description>Number of adverse events reported</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amputation-free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Number of survived patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Limb salvage from major amputation</measure>
    <time_frame>3, 6, 12, 24 months</time_frame>
    <description>Number of patients who avoided amputation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relief of the rest pain</measure>
    <time_frame>Immediate, 3, 6, 12, 24 months</time_frame>
    <description>Rest pain will be measured using the rest pain scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in healing trophic disorders</measure>
    <time_frame>Immediate, 3, 6, 12, 24 months</time_frame>
    <description>Assessment of the severity of trophic ulcers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in perfusion by the ankle-brachial index</measure>
    <time_frame>Immediate, 3, 6, 12, 24 months</time_frame>
    <description>Measurements of the ankle-brachial index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in perfusion by radioisotope scintigraphy</measure>
    <time_frame>Immediate, 3, 6, 12, 24 months</time_frame>
    <description>Radioisotope scintigraphy study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in total walking distance (TWD) using a standard treadmill test</measure>
    <time_frame>Immediate, 3, 6, 12, 24 months</time_frame>
    <description>Standard treadmill test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Critical Limb Ischemia</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mesenchymal stem cells, Intramuscular injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline, Intramuscular injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mesenchymal stem cells</intervention_name>
    <description>Intramuscular injection</description>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>Intramuscular injection</description>
    <arm_group_label>Normal saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females in the age group of 18-80 yrs of Caucasian origin.&#xD;
&#xD;
          2. Peripheral artery disease (PAD) against the background of atherosclerosis and diabetes&#xD;
             mellitus (DM)&#xD;
&#xD;
          3. Critical lower limb ischemia (stages 3-4 by Fontaine-Pokrovsky or stages 4-6 by&#xD;
             Rutherford)&#xD;
&#xD;
          4. Patients with remaining symptoms of critical limb ischemia (CLI) in spite of the&#xD;
             performed surgical (endovascular or open) treatment and continuing conservative&#xD;
             therapy&#xD;
&#xD;
          5. Patients with absent emergency indications to major amputation&#xD;
&#xD;
          6. Patients planned for the reconstructive surgery with a questionable remote outcome due&#xD;
             to compromised blood outflow&#xD;
&#xD;
          7. Ankle Brachial Pressure Index (ABPI) ≤ 0.5 or ankle pressure ≤ 70 mm Hg&#xD;
&#xD;
          8. Patients, if having associated Type II Diabetes, should be on medication and well&#xD;
             controlled (HbA1c ≤ 8.5 %)&#xD;
&#xD;
          9. On regular medication for hypertension if needed&#xD;
&#xD;
         10. Normal liver and renal function (or having clinically insignificant deviations,&#xD;
             according to the treating physician's opinion)&#xD;
&#xD;
         11. Patients who are able to understand the requirements of the study, and willing to&#xD;
             provide voluntary written informed consent, abide by the study requirements, and agree&#xD;
             to return for required follow-up visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Humid gangrene or acute/chronic infection of lower limb.&#xD;
&#xD;
          2. Dry gangrene with extensive foot lesion (&gt; 1\2).&#xD;
&#xD;
          3. Acute arterial failure.&#xD;
&#xD;
          4. Life-threatening conditions and predicted life expectancy of &lt; 6 months.&#xD;
&#xD;
          5. Presence of neoplasm or bone marrow disease&#xD;
&#xD;
          6. Signs of active or chronic, including latent, haemorrhage&#xD;
&#xD;
          7. Any acute or chronic infectious disease&#xD;
&#xD;
          8. Renal failure determined as twofold or higher elevation of serum creatinine as&#xD;
             compared to the upper normal limit&#xD;
&#xD;
          9. Hepatic failure determined as the bilirubin, alanine aminotransferase (ALT) or&#xD;
             aspartate aminotransferase (AST) levels elevated by two and more times over the upper&#xD;
             normal limits&#xD;
&#xD;
         10. Thrombocytopenia (platelet counts &lt; 50,000 /µl), leukocytopenia (WBC &lt; 4,000/µl),&#xD;
             immunosuppressive therapy&#xD;
&#xD;
         11. Pronounced neurological deficit&#xD;
&#xD;
         12. Patients with gait disturbance for reasons other than CLI&#xD;
&#xD;
         13. Patients not suitable for cell therapy, by the treating physician's opinion&#xD;
&#xD;
         14. CLI patients requiring amputation at the proximal to the trans-metatarsal level&#xD;
&#xD;
         15. Patients with Type I diabetes&#xD;
&#xD;
         16. Patients having respiratory complications/left ventricular ejection fraction &lt; 25%&#xD;
&#xD;
         17. Stroke or myocardial infarction within last 3 months&#xD;
&#xD;
         18. Patients who are contraindicated for X-ray angiography&#xD;
&#xD;
         19. History of severe alcohol or drug abuse within 3 months of screening&#xD;
&#xD;
         20. Pregnant and lactating women.&#xD;
&#xD;
         21. Patients tested positive for HIV 1, hepatitis C virus (HCV), hepatitis B virus (HBV)&#xD;
&#xD;
         22. Unsigned informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vladimir P Baklaushev, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Deputy Director</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pavel Yu Orekhov, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vascular Surgeon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mikhail A Konoplyannikov, PhD</last_name>
    <phone>+79154027268</phone>
    <email>mkonopl@mail.ru</email>
  </overall_contact>
  <location>
    <facility>
      <name>Federal Research Clinical Center of Federal Medical &amp; Biological Agency</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mikhail A Konoplyannikov, PhD</last_name>
      <phone>+79154027268</phone>
      <email>mkonopl@mail.ru</email>
    </contact>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>August 1, 2017</last_update_submitted>
  <last_update_submitted_qc>August 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2017</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>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03239535
org study id: MSC-CLI/FMBA/001
nct id: NCT03239535
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The clinical trial aims to study the safety and efficacy of adult allogeneic mesenchymal stem
      cells for the treatment of critical limb ischemia.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Adverse events
time frame: 24 months
description: Number of adverse events reported
measure: Amputation-free survival
time frame: 24 months
description: Number of survived patients
measure: Limb salvage from major amputation
time frame: 3, 6, 12, 24 months
description: Number of patients who avoided amputation
measure: Relief of the rest pain
time frame: Immediate, 3, 6, 12, 24 months
description: Rest pain will be measured using the rest pain scale
measure: Improvement in healing trophic disorders
time frame: Immediate, 3, 6, 12, 24 months
description: Assessment of the severity of trophic ulcers
measure: Improvement in perfusion by the ankle-brachial index
time frame: Immediate, 3, 6, 12, 24 months
description: Measurements of the ankle-brachial index
measure: Improvement in perfusion by radioisotope scintigraphy
time frame: Immediate, 3, 6, 12, 24 months
description: Radioisotope scintigraphy study
measure: Improvement in total walking distance (TWD) using a standard treadmill test
time frame: Immediate, 3, 6, 12, 24 months
description: Standard treadmill test
arm group label: Mesenchymal stem cells
arm group type: Experimental
description: Mesenchymal stem cells, Intramuscular injection
arm group label: Normal saline
arm group type: Placebo Comparator
description: Normal saline, Intramuscular injection
intervention type: Biological
intervention name: Mesenchymal stem cells
description: Intramuscular injection
arm group label: Mesenchymal stem cells
intervention type: Biological
intervention name: Normal saline
description: Intramuscular injection
arm group label: Normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Vladimir P Baklaushev, MD, PhD
role: Study Director
affiliation: Deputy Director
last name: Pavel Yu Orekhov, MD, PhD
role: Principal Investigator
affiliation: Vascular Surgeon
last name: Mikhail A Konoplyannikov, PhD
phone: +79154027268
email: mkonopl@mail.ru
facility: 
status: Recruiting
contact: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Ischemia
sharing ipd: No