xml: <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/NCT05978011</url>
    </required_header>
    <id_info>
      <org_study_id>2014TP001</org_study_id>
      <nct_id>NCT05978011</nct_id>
    </id_info>
    <brief_title>2014TP001 - Assessing the Biology of the Injured Lung - Version 1</brief_title>
    <official_title>Assessing the Biology of the Injured Lung - Version 1</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Manchester University NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Manchester University NHS Foundation Trust</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Respiratory diseases are very common and are the third leading cause of death in England. As&#xD;
        such, there is strong interest in understanding how respiratory disease occurs.&#xD;
  &#xD;
        This study intends to understand the changes that occur within diseased/injured lungs&#xD;
        obtained from humans. The end goal of this will be to create new drugs to help treat these&#xD;
        disorders.&#xD;
  &#xD;
        Diseased lungs will be obtained from patients receiving a lung transplant. Lungs will either&#xD;
        be placed onto a heart-lung machine, or surgically cut in order to create a model of the lung&#xD;
        that can be used experimentally in the laboratory. Using a heart-lung machine, lungs can be&#xD;
        maintained outside of the human body for a maximum of 12 hours, allowing the direct&#xD;
        assessment of the organ. Using this procedure, we aim to understand the processes that occur&#xD;
        within a disease, as well as during repair. Using the model of the lung, we will look at how&#xD;
        the body's immune system interacts within a diseased lung.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">August 29, 2014</start_date>
    <completion_date type="Actual">April 4, 2019</completion_date>
    <primary_completion_date type="Actual">April 4, 2019</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>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>To identify the mechanisms that occur during lung inflammation, injury and repair and the contribution of immune cells to these processes.</measure>
      <time_frame>Prior to lung transplantation.</time_frame>
      <description>Cytokines and chemokines within lungs will be assessed to determine inflammatory profiles. This will be done using luminex arrays that allow quantification of a range of immunologic molecules in bronchoalveolar lavage and perfusate samples. This will provide a broad overview of the prevailing local tissue environment. We will also assess this following immunomodulation as this may be significantly altered by the presence of immunomodulatory therapeutics.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Characterise the migration and functional profile of immune cells within the inflamed/damaged lung.</measure>
      <time_frame>Prior to lung transplantation</time_frame>
      <description>Immune cells obtained from the lungs on the EVLP circuit and cells cultured in the air liquid model will be incubated with antibodies that target specific cellular markers for the detection using flow cytometry. Immune cells can then be characterised and their function determined. The behavioural characteristics and activation status of immune cells will also be determined using flow cytometry, ELISpot/ELISA, immunohistochemistry and qPCR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assess the effectiveness of therapeutic agents that can repair lung damage.</measure>
      <time_frame>Prior to lung transplantation</time_frame>
      <description>Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Trial therapeutic agents that can modulate the effect of immune cells in response to lung tissue injury.</measure>
      <time_frame>Prior to lung transplantation</time_frame>
      <description>Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identify new therapeutic targets/agents that can reduce the incidence/severity of inflammatory respiratory conditions.</measure>
      <time_frame>Prior to lung transplantation</time_frame>
      <description>PDiseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cut sections of the lung to culture in an in vitro lung model to assess the effect of various different mechanisms of injury on the function and characteristics of immune cells.</measure>
      <time_frame>Prior to lung transplantation</time_frame>
      <description>Lungs will be dissected to be used in an in vitro model, generating a morphologically accurate model of the lung. This model will then be used to assess immune cell characteristics.</description>
    </secondary_outcome>
    <enrollment type="Actual">119</enrollment>
    <condition>Respiratory Diseases</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Respiratory disorders - lung transplantation&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients must be able to provide informed consent&#xD;
  &#xD;
            -  Patients must be aged between 18-80 years of age&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          -Patients under 16 or over 70 years of age&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 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>Respiratory Tract Diseases</mesh_term>
      <mesh_term>Respiration Disorders</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05978011
  org study id: 2014TP001
  nct id: NCT05978011
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Respiratory diseases are very common and are the third leading cause of death in England. As
        such, there is strong interest in understanding how respiratory disease occurs.
  
        This study intends to understand the changes that occur within diseased/injured lungs
        obtained from humans. The end goal of this will be to create new drugs to help treat these
        disorders.
  
        Diseased lungs will be obtained from patients receiving a lung transplant. Lungs will either
        be placed onto a heart-lung machine, or surgically cut in order to create a model of the lung
        that can be used experimentally in the laboratory. Using a heart-lung machine, lungs can be
        maintained outside of the human body for a maximum of 12 hours, allowing the direct
        assessment of the organ. Using this procedure, we aim to understand the processes that occur
        within a disease, as well as during repair. Using the model of the lung, we will look at how
        the body's immune system interacts within a diseased lung.
  observational model: Cohort
  time perspective: Prospective
  measure: To identify the mechanisms that occur during lung inflammation, injury and repair and the contribution of immune cells to these processes.
  time frame: Prior to lung transplantation.
  description: Cytokines and chemokines within lungs will be assessed to determine inflammatory profiles. This will be done using luminex arrays that allow quantification of a range of immunologic molecules in bronchoalveolar lavage and perfusate samples. This will provide a broad overview of the prevailing local tissue environment. We will also assess this following immunomodulation as this may be significantly altered by the presence of immunomodulatory therapeutics.
  measure: Characterise the migration and functional profile of immune cells within the inflamed/damaged lung.
  time frame: Prior to lung transplantation
  description: Immune cells obtained from the lungs on the EVLP circuit and cells cultured in the air liquid model will be incubated with antibodies that target specific cellular markers for the detection using flow cytometry. Immune cells can then be characterised and their function determined. The behavioural characteristics and activation status of immune cells will also be determined using flow cytometry, ELISpot/ELISA, immunohistochemistry and qPCR.
  measure: Assess the effectiveness of therapeutic agents that can repair lung damage.
  time frame: Prior to lung transplantation
  description: Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
  measure: Trial therapeutic agents that can modulate the effect of immune cells in response to lung tissue injury.
  time frame: Prior to lung transplantation
  description: Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
  measure: Identify new therapeutic targets/agents that can reduce the incidence/severity of inflammatory respiratory conditions.
  time frame: Prior to lung transplantation
  description: PDiseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs. The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution. Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored. We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
  measure: Cut sections of the lung to culture in an in vitro lung model to assess the effect of various different mechanisms of injury on the function and characteristics of immune cells.
  time frame: Prior to lung transplantation
  description: Lungs will be dissected to be used in an in vitro model, generating a morphologically accurate model of the lung. This model will then be used to assess immune cell characteristics.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Respiratory Tract Diseases
  mesh term: Respiration Disorders