<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/NCT01668576</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00053075</org_study_id>
    <nct_id>NCT01668576</nct_id>
  </id_info>
  <brief_title>Properties of Mesenchymal Stem Cells in Lung Transplant</brief_title>
  <official_title>Properties of Mesenchymal Stem Cells in Lung Transplant Candidates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The major limitation to long term survival in lung transplant recipients is the development&#xD;
      of graft failure over time, termed bronchiolitis obliterans. The conventional therapies used&#xD;
      to prevent rejection are not effective in preventing bronchiolitis obliterans. Therefore, new&#xD;
      therapies are needed to address this problem. A growing body of research has focused on a&#xD;
      unique population of bone marrow cells termed Mesenchymal Stem Cells (MSCs) to improve a&#xD;
      range of medical conditions including heart failure, autoimmune disease, and inflammatory&#xD;
      bowel disease. MSCs can prevent animal models of bronchiolitis obliterans. Because of this&#xD;
      information, it is plausible that MSCs could help patients as a potential treatment in lung&#xD;
      transplantation.&#xD;
&#xD;
      This proposal will test the immunologic properties of MSCs generated from such individuals to&#xD;
      answer the question of whether generation of whether it would be feasible to use such cells&#xD;
      in the future to prevent entities such as bronchiolitis obliterans.&#xD;
&#xD;
      The Investigator will approach patients who are being considered for a lung transplant&#xD;
      because of end stage lung disease. Enrolled patients will undergo a bone marrow aspiration&#xD;
      where a small amount of fluid is removed from their pelvic bone. Cells obtained in this&#xD;
      procedure will be expanded in the Emory/Georgia Tech Cell Lab. MSCs will be expanded in this&#xD;
      lab using cell culture conditions which are standardly used for MSCs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Problem of Interest: Lung transplantation represents a potential therapy for patients with&#xD;
      end-stage lung diseases such as pulmonary fibrosis, emphysema and cystic fibrosis. The major&#xD;
      limitation to long term survival in lung transplant recipients is the development of graft&#xD;
      failure over time, termed bronchiolitis obliterans. The conventional therapies used to&#xD;
      prevent rejection are not effective in preventing bronchiolitis obliterans. Therefore, new&#xD;
      therapies are needed to address this problem. A growing body of research has focused on a&#xD;
      unique population of bone marrow cells termed Mesenchymal Stem Cells (MSCs) to improve a&#xD;
      range of medical conditions including heart failure, autoimmune disease, and inflammatory&#xD;
      bowel disease. MSCs can prevent animal models of bronchiolitis obliterans. Because of this&#xD;
      information, it is plausible that MSCs could help patients as a potential treatment in lung&#xD;
      transplantation. MSCs can be obtained from 2 sources: commercially available MSCs which are&#xD;
      generated from other normal volunteers and from the patient themselves. When MSCs are&#xD;
      obtained from the patient for whom they are used, they are termed &quot;autologous MSCs&quot;. A major&#xD;
      potential drawback to the use of commercially available MSCs is that these cells contain&#xD;
      proteins from other individuals which could provoke rejection when used in lung transplant&#xD;
      recipients. Therefore, the use of autologous MSCs currently appears the most attractive&#xD;
      option. What is not understood at the present time is the extent to which autologous MSCs&#xD;
      obtained from chronically ill patients with end-stage lung disease still maintain properties&#xD;
      which would be beneficial. This proposal will test the immunologic properties of MSCs&#xD;
      generated from such individuals to answer the question of whether generation of whether it&#xD;
      would be feasible to use such cells in the future to prevent entities such as bronchiolitis&#xD;
      obliterans.&#xD;
&#xD;
      Overview on how this will be studied: The Investigator will approach patients who are being&#xD;
      considered for a lung transplant because of end stage lung disease. Enrolled patients will&#xD;
      undergo a bone marrow aspiration where a small amount of fluid is removed from their pelvic&#xD;
      bone. Cells obtained in this procedure will be expanded in the Emory/Georgia Tech Cell Lab.&#xD;
      MSCs will be expanded in this lab using cell culture conditions which are standardly used for&#xD;
      MSCs. The Investigator will test the efficiency of expansion of these MSCs to determine if&#xD;
      they can be obtained from all patients, or if there some patients demonstrate inefficient MSC&#xD;
      expansion based on age or disease or other factors. The Investigator will then test in-vitro&#xD;
      the ability of MSCs from different patients to prevent activation of the immune system when&#xD;
      faced with proteins from other individuals. The Investigator believes this model system&#xD;
      approximates the type of interaction that would occur if these MSCs were given to patients&#xD;
      who received a lung transplant.&#xD;
&#xD;
      Benefit of research to knowledge and human health: It is not presently known whether patients&#xD;
      with severe medical illness are able to have MSCs expanded. If it is found that MSCs can be&#xD;
      readily obtained from such individuals and additionally find that such MSCs have properties&#xD;
      which would be predicted to be beneficial in lung transplant, this study would provide the&#xD;
      rationale to use MSCs as a therapeutic agent in patients undergoing lung transplantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Loss of funding&#xD;
  </why_stopped>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Intrinsic variability of MSCs measured by time to third passage of confluent MSC</measure>
    <time_frame>Post Co-Culture (24 hours)</time_frame>
    <description>Assess for intrinsic variability of MSCs derived from individuals with end-stage lung disease across a range of ages, disease types, and comorbid conditions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-3 IDO production measured as ug/mL of passage 3 MSCs</measure>
    <time_frame>Post Co-Culture (24 hours)</time_frame>
    <description>Demonstrate autologous MSCs have in-vitro immunoregulatory properties against allo-specific T cell responses and compare the MSC effects to conditioned media from MSCs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent specific inhibition of CD4 and CD8 T cell proliferation toward donor target cells in one way mixed-lymphocyte reactions</measure>
    <time_frame>Post Co-Culture (24 hours)</time_frame>
    <description>Test the immunoregulatory properties of MSCs in the setting of conventional levels of immune suppression</description>
  </primary_outcome>
  <enrollment type="Actual">4</enrollment>
  <condition>Lung Transplantation</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      mesenchymal stem cells derived from subject bone marrow aspiration&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Lung transplant candidates&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18-70 without regard to race or gender&#xD;
&#xD;
          -  End stage lung disease from IPF, cystic fibrosis, emphysema, sarcoidosis or pulmonary&#xD;
             hypertension&#xD;
&#xD;
          -  Expected time from enrollment to transplant greater than 4 weeks&#xD;
&#xD;
          -  Patient willing to undergo a bone marrow aspiration prior to transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under age 18&#xD;
&#xD;
          -  Patients on significant immunosuppressive agents prior to transplant (specifically&#xD;
             calcineurin inhibitors, cell cycle inhibitors or prednisone &gt;0.5 mg/kg lean body&#xD;
             weight)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Neujahr, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>January 13, 2016</last_update_submitted>
  <last_update_submitted_qc>January 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>David C Neujahr, MD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>mesenchymal stem cells</keyword>
  <keyword>Lung transplantation</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/NCT01668576
org study id: IRB00053075
nct id: NCT01668576
lead sponsor: 
has dmc: No
The major limitation to long term survival in lung transplant recipients is the development
      of graft failure over time, termed bronchiolitis obliterans. The conventional therapies used
      to prevent rejection are not effective in preventing bronchiolitis obliterans. Therefore, new
      therapies are needed to address this problem. A growing body of research has focused on a
      unique population of bone marrow cells termed Mesenchymal Stem Cells (MSCs) to improve a
      range of medical conditions including heart failure, autoimmune disease, and inflammatory
      bowel disease. MSCs can prevent animal models of bronchiolitis obliterans. Because of this
      information, it is plausible that MSCs could help patients as a potential treatment in lung
      transplantation.

      This proposal will test the immunologic properties of MSCs generated from such individuals to
      answer the question of whether generation of whether it would be feasible to use such cells
      in the future to prevent entities such as bronchiolitis obliterans.

      The Investigator will approach patients who are being considered for a lung transplant
      because of end stage lung disease. Enrolled patients will undergo a bone marrow aspiration
      where a small amount of fluid is removed from their pelvic bone. Cells obtained in this
      procedure will be expanded in the Emory/Georgia Tech Cell Lab. MSCs will be expanded in this
      lab using cell culture conditions which are standardly used for MSCs.
Problem of Interest: Lung transplantation represents a potential therapy for patients with
      end-stage lung diseases such as pulmonary fibrosis, emphysema and cystic fibrosis. The major
      limitation to long term survival in lung transplant recipients is the development of graft
      failure over time, termed bronchiolitis obliterans. The conventional therapies used to
      prevent rejection are not effective in preventing bronchiolitis obliterans. Therefore, new
      therapies are needed to address this problem. A growing body of research has focused on a
      unique population of bone marrow cells termed Mesenchymal Stem Cells (MSCs) to improve a
      range of medical conditions including heart failure, autoimmune disease, and inflammatory
      bowel disease. MSCs can prevent animal models of bronchiolitis obliterans. Because of this
      information, it is plausible that MSCs could help patients as a potential treatment in lung
      transplantation. MSCs can be obtained from 2 sources: commercially available MSCs which are
      generated from other normal volunteers and from the patient themselves. When MSCs are
      obtained from the patient for whom they are used, they are termed "autologous MSCs". A major
      potential drawback to the use of commercially available MSCs is that these cells contain
      proteins from other individuals which could provoke rejection when used in lung transplant
      recipients. Therefore, the use of autologous MSCs currently appears the most attractive
      option. What is not understood at the present time is the extent to which autologous MSCs
      obtained from chronically ill patients with end-stage lung disease still maintain properties
      which would be beneficial. This proposal will test the immunologic properties of MSCs
      generated from such individuals to answer the question of whether generation of whether it
      would be feasible to use such cells in the future to prevent entities such as bronchiolitis
      obliterans.

      Overview on how this will be studied: The Investigator will approach patients who are being
      considered for a lung transplant because of end stage lung disease. Enrolled patients will
      undergo a bone marrow aspiration where a small amount of fluid is removed from their pelvic
      bone. Cells obtained in this procedure will be expanded in the Emory/Georgia Tech Cell Lab.
      MSCs will be expanded in this lab using cell culture conditions which are standardly used for
      MSCs. The Investigator will test the efficiency of expansion of these MSCs to determine if
      they can be obtained from all patients, or if there some patients demonstrate inefficient MSC
      expansion based on age or disease or other factors. The Investigator will then test in-vitro
      the ability of MSCs from different patients to prevent activation of the immune system when
      faced with proteins from other individuals. The Investigator believes this model system
      approximates the type of interaction that would occur if these MSCs were given to patients
      who received a lung transplant.

      Benefit of research to knowledge and human health: It is not presently known whether patients
      with severe medical illness are able to have MSCs expanded. If it is found that MSCs can be
      readily obtained from such individuals and additionally find that such MSCs have properties
      which would be predicted to be beneficial in lung transplant, this study would provide the
      rationale to use MSCs as a therapeutic agent in patients undergoing lung transplantation.
observational model: Cohort
time perspective: Cross-Sectional
measure: Intrinsic variability of MSCs measured by time to third passage of confluent MSC
time frame: Post Co-Culture (24 hours)
description: Assess for intrinsic variability of MSCs derived from individuals with end-stage lung disease across a range of ages, disease types, and comorbid conditions
measure: 2-3 IDO production measured as ug/mL of passage 3 MSCs
time frame: Post Co-Culture (24 hours)
description: Demonstrate autologous MSCs have in-vitro immunoregulatory properties against allo-specific T cell responses and compare the MSC effects to conditioned media from MSCs
measure: Percent specific inhibition of CD4 and CD8 T cell proliferation toward donor target cells in one way mixed-lymphocyte reactions
time frame: Post Co-Culture (24 hours)
description: Test the immunoregulatory properties of MSCs in the setting of conventional levels of immune suppression
mesenchymal stem cells derived from subject bone marrow aspiration
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: David Neujahr, MD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: David C Neujahr, MD
investigator title: Assistant Professor