<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/NCT02260375</url>
  </required_header>
  <id_info>
    <org_study_id>MSC liver transplant tolerance</org_study_id>
    <secondary_id>2014-001531-37</secondary_id>
    <nct_id>NCT02260375</nct_id>
  </id_info>
  <brief_title>MSC Therapy in Liver Transplantation</brief_title>
  <official_title>THIRD-PARTY BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS TO INDUCE TOLERANCE IN LIVER TRANSPLANT RECIPIENTS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Monia Lorini</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mario Negri Institute for Pharmacological Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>A.O. Ospedale Papa Giovanni XXIII</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The general aim of the present study is to test a cell therapy with third-party allogeneic&#xD;
      ex-vivo expanded MSCs as a strategy to induce tolerance in liver transplant recipients. MSCs&#xD;
      will be prepared accordingly to established protocols , starting from diagnostic samples of&#xD;
      bone marrow aspirates (2-5 mL) or using the remnants in the bag and filter at the end of the&#xD;
      bone marrow infusions. From these samples, MSCs will be expanded in GMP approved facilities&#xD;
      and used for the present study in patients undergoing liver transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events</measure>
    <time_frame>Changes from baseline up to 120 month.</time_frame>
    <description>At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Liver tissue mRNA level of Transferrin receptor CD71 (TFRC) and Hepcidin antimicrobial peptide (HAMP) genes</measure>
    <time_frame>At 12 and 60 month.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Circulating naive and memory T cell conts (CD45RA/CD45RO)(flow cytometry analysis)</measure>
    <time_frame>Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>T-cell function in mixed lymphocyte reaction</measure>
    <time_frame>Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Liver Transplant Rejection</condition>
  <arm_group>
    <arm_group_label>Mesenchymal Stromal Cells (MSC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party MSC (from healthy donors) will be performed in patients assigned to the MSC procedure in addition to the liver transplantation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No treatment.</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mesenchymal Stromal Cells</intervention_name>
    <arm_group_label>Mesenchymal Stromal Cells (MSC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For this study, the following inclusion criteria should be fulfilled before starting&#xD;
        withdrawal of drugs after 1 year post-transplant:&#xD;
&#xD;
          -  First liver transplant&#xD;
&#xD;
          -  Capable of understanding the purpose and risk of the study&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Specific contraindication to MSC infusion&#xD;
&#xD;
          -  Any clinical relevant condition that might affect study participation and/or study&#xD;
             results&#xD;
&#xD;
          -  Pregnant women and nursing mothers&#xD;
&#xD;
          -  Unwillingness or inability to follow the study protocol in the investigator's opinion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giuseppe Remuzzi, MD</last_name>
    <role>Study Chair</role>
    <affiliation>A.O. Ospedale Papa Giovanni XXIII</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Norberto Perico, MD</last_name>
    <role>Study Director</role>
    <affiliation>IRCCS-Istituto di Ricerche Farmacologiche M. Negri</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michele Colledan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>A.O. Ospedale Papa Giovanni XXIII</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stefano Fagiuoli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>A.O. Ospedale Papa Giovanni XXIII</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Martino Introna, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laboratorio G.Lanzani, Bergamo, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alessandro Rambaldi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>A.O. Ospedale Papa Giovanni XXIII</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Pinna, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Policlinico S. Orsola Bologna, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Claudio Velati, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Policlinico S. Orsola Bologna, Italy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Giuseppe Remuzzi, MD</last_name>
    <phone>0039 0352674037</phone>
    <email>gremuzzi@hpg23.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>U.S.C Nefrologia e Dialisi</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giuseppe Remuzzi, MD</last_name>
      <phone>0039 0352674037</phone>
      <email>gremuzzi@hpg23.it</email>
    </contact>
    <investigator>
      <last_name>Giuseppe Remuzzi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>USC Chirurgia Generale III</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Colledan, Md</last_name>
      <phone>00390352674347</phone>
      <email>mcolledan@hpg23.it</email>
    </contact>
    <investigator>
      <last_name>Marco Zambelli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>USC Ematologia</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Rambaldi, MD</last_name>
      <phone>00390352673684</phone>
      <email>arambaldi@hpg23.it</email>
    </contact>
    <investigator>
      <last_name>Alessandro Rambaldi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>USC Gastroenterologia</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefano Fagiuoli, MD</last_name>
      <phone>00390352674259</phone>
      <email>sfagiuoli@hpg23.it</email>
    </contact>
    <investigator>
      <last_name>Giulia Magini, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Servizio di Immunoematologia e Medicina Trasfusionale</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudio Velati, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Marina Buzzi, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Claudio Velati, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Unità Chirurgia Generale e Trapianti</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonio Pinna, MD</last_name>
    </contact>
    <investigator>
      <last_name>Antonio Pinna, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>April 5, 2018</last_update_submitted>
  <last_update_submitted_qc>April 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>A.O. Ospedale Papa Giovanni XXIII</investigator_affiliation>
    <investigator_full_name>Monia Lorini</investigator_full_name>
    <investigator_title>EC Secretary</investigator_title>
  </responsible_party>
  <keyword>Mesenchymal stromal cells; liver transplantation; tolerance.</keyword>
  <!-- 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/NCT02260375
org study id: MSC liver transplant tolerance
secondary id: 2014-001531-37
nct id: NCT02260375
lead sponsor: 
collaborator: 
has dmc: No
The general aim of the present study is to test a cell therapy with third-party allogeneic
      ex-vivo expanded MSCs as a strategy to induce tolerance in liver transplant recipients. MSCs
      will be prepared accordingly to established protocols , starting from diagnostic samples of
      bone marrow aspirates (2-5 mL) or using the remnants in the bag and filter at the end of the
      bone marrow infusions. From these samples, MSCs will be expanded in GMP approved facilities
      and used for the present study in patients undergoing liver transplantation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events
time frame: Changes from baseline up to 120 month.
description: At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded.
measure: Liver tissue mRNA level of Transferrin receptor CD71 (TFRC) and Hepcidin antimicrobial peptide (HAMP) genes
time frame: At 12 and 60 month.
measure: Circulating naive and memory T cell conts (CD45RA/CD45RO)(flow cytometry analysis)
time frame: Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.
measure: T-cell function in mixed lymphocyte reaction
time frame: Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.
arm group label: Mesenchymal Stromal Cells (MSC)
arm group type: Experimental
description: A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party MSC (from healthy donors) will be performed in patients assigned to the MSC procedure in addition to the liver transplantation.
arm group label: No treatment.
arm group type: No Intervention
intervention type: Biological
intervention name: Mesenchymal Stromal Cells
arm group label: Mesenchymal Stromal Cells (MSC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giuseppe Remuzzi, MD
role: Study Chair
affiliation: A.O. Ospedale Papa Giovanni XXIII
last name: Norberto Perico, MD
role: Study Director
affiliation: IRCCS-Istituto di Ricerche Farmacologiche M. Negri
last name: Michele Colledan, MD
role: Principal Investigator
affiliation: A.O. Ospedale Papa Giovanni XXIII
last name: Stefano Fagiuoli, MD
role: Principal Investigator
affiliation: A.O. Ospedale Papa Giovanni XXIII
last name: Martino Introna, MD
role: Principal Investigator
affiliation: Laboratorio G.Lanzani, Bergamo, Italy
last name: Alessandro Rambaldi, MD
role: Principal Investigator
affiliation: A.O. Ospedale Papa Giovanni XXIII
last name: Antonio Pinna, MD
role: Principal Investigator
affiliation: Policlinico S. Orsola Bologna, Italy
last name: Claudio Velati, MD
role: Principal Investigator
affiliation: Policlinico S. Orsola Bologna, Italy
last name: Giuseppe Remuzzi, MD
phone: 0039 0352674037
email: gremuzzi@hpg23.it
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
responsible party type: Sponsor-Investigator
investigator affiliation: A.O. Ospedale Papa Giovanni XXIII
investigator full name: Monia Lorini
investigator title: EC Secretary