<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/NCT03815864</url>
  </required_header>
  <id_info>
    <org_study_id>106961</org_study_id>
    <nct_id>NCT03815864</nct_id>
  </id_info>
  <brief_title>Antibodies and Liver Retransplantation</brief_title>
  <official_title>Role of Donor Specific Antibodies, Other Anti-human Leucocyte Antibodies and Autoantibodies in the Outcome of Liver Retransplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>London Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>London Health Sciences Centre</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>
      Despite reports that associate donor specific antibody (DSA) with rejection after liver&#xD;
      transplantation, grafts are still allocated according to blood group (ABO) but not human&#xD;
      leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible&#xD;
      clinical association between adverse recipient outcome and DSA. Re-transplantation provides a&#xD;
      test environment where the presence of preformed DSA or other antibodies is prevalent and&#xD;
      events (graft loss) more common so that the effect of these antibodies on outcome should be&#xD;
      apparent. This is an observational study of routine clinical care to determine these effects&#xD;
      on our own patients. The goal is to perfect donor-recipient matching to attain the best&#xD;
      outcome. In addition, we may develop hypotheses and potential treatments that would be tested&#xD;
      in further clinical trials&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite reports that associate donor specific antibody (DSA) with rejection after liver&#xD;
      transplantation, grafts are still allocated according to blood group (ABO) but not human&#xD;
      leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible&#xD;
      clinical association between adverse recipient outcome and DSA. Re-transplantation provides a&#xD;
      test environment where the presence of preformed DSA or other antibodies is prevalent and&#xD;
      events (graft loss) more common so that the effect of these antibodies on outcome should be&#xD;
      apparent. This is an observational study of routine clinical care to determine these effects&#xD;
      on our own patients.&#xD;
&#xD;
      In phase 1, we will examine the effect of antibodies specifically directed against the second&#xD;
      donor in liver retransplantation. Other factors known to effect the outcome will be checked&#xD;
      to allow for risk adjustment.&#xD;
&#xD;
      In phase 2, we will examine the role played by specific auto-antibodies such as angiotensin&#xD;
      II receptor type 1 antibodies and endothelin-1 type A receptor antibodies on the outcome of&#xD;
      liver retransplantation.&#xD;
&#xD;
      The goal of these observational study is to perfect donor-recipient matching to attain the&#xD;
      best outcome. In addition, we may develop hypotheses and potential treatments that would be&#xD;
      tested in further clinical trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 1977</start_date>
  <completion_date type="Anticipated">January 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2021</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Retransplant graft survival</measure>
    <time_frame>From date of transplantation until the date of next transplantation or date of death from any cause, whichever came first, assessed up to 240 months</time_frame>
    <description>Average length of time the second liver graft remains in a living recipient regardless of function</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient survival</measure>
    <time_frame>From date of transplantation until the date of death from any cause assessed up to 240 months</time_frame>
    <description>Average length of time a recipient is alive regardless of presence of the second liver transplant</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Acute rejection</measure>
    <time_frame>From date of transplantation until the date of first documented acute rejection assessed up to 240 months</time_frame>
    <description>number of participants with a clinically diagnosed and treated episode of rejection (either acute cellular or humoral)</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Liver Transplant Failure</condition>
  <condition>Antibody-mediated Rejection</condition>
  <arm_group>
    <arm_group_label>D2SA+</arm_group_label>
    <description>Median fluoresce intensity &gt; or = 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D2SA-</arm_group_label>
    <description>Median fluoresce intensity &lt; 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation</intervention_name>
    <description>Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)</description>
    <arm_group_label>D2SA+</arm_group_label>
    <arm_group_label>D2SA-</arm_group_label>
    <other_name>AT1R antibody</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and tissue samples stored for clinical use by the Transplant Laboratory since the&#xD;
      beginning of liver transplantation at our facility in 1977&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        all patients who have undergone a repeat transplantation of the liver at LHSC.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Recipients of a second liver transplantation performed at LHSC&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recipients of ABO incompatible second liver transplantation&#xD;
&#xD;
          -  Recipients of multiple organs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vivian McAlister</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Health Sciences Center</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 20, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>January 24, 2019</last_update_submitted>
  <last_update_submitted_qc>January 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>London Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Vivian McAlister</investigator_full_name>
    <investigator_title>Professor of Surgery</investigator_title>
  </responsible_party>
  <keyword>donor specific antibody</keyword>
  <keyword>autoantibody</keyword>
  <keyword>human leucocyte antigen</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>From publication until 5 years later</ipd_time_frame>
    <ipd_access_criteria>De-identified subject level data will be shared with researchers who contact the principal investigator, submit a research plan and sign an agreement. Approval by Western Research Ethics may be required depending on the request.</ipd_access_criteria>
  </patient_data>
  <pending_results>
    <submitted>April 4, 2022</submitted>
    <returned>October 18, 2022</returned>
    <submitted>October 18, 2022</submitted>
    <returned>August 29, 2023</returned>
  </pending_results>
  <!-- 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/NCT03815864
org study id: 106961
nct id: NCT03815864
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Despite reports that associate donor specific antibody (DSA) with rejection after liver
      transplantation, grafts are still allocated according to blood group (ABO) but not human
      leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible
      clinical association between adverse recipient outcome and DSA. Re-transplantation provides a
      test environment where the presence of preformed DSA or other antibodies is prevalent and
      events (graft loss) more common so that the effect of these antibodies on outcome should be
      apparent. This is an observational study of routine clinical care to determine these effects
      on our own patients. The goal is to perfect donor-recipient matching to attain the best
      outcome. In addition, we may develop hypotheses and potential treatments that would be tested
      in further clinical trials
Despite reports that associate donor specific antibody (DSA) with rejection after liver
      transplantation, grafts are still allocated according to blood group (ABO) but not human
      leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible
      clinical association between adverse recipient outcome and DSA. Re-transplantation provides a
      test environment where the presence of preformed DSA or other antibodies is prevalent and
      events (graft loss) more common so that the effect of these antibodies on outcome should be
      apparent. This is an observational study of routine clinical care to determine these effects
      on our own patients.

      In phase 1, we will examine the effect of antibodies specifically directed against the second
      donor in liver retransplantation. Other factors known to effect the outcome will be checked
      to allow for risk adjustment.

      In phase 2, we will examine the role played by specific auto-antibodies such as angiotensin
      II receptor type 1 antibodies and endothelin-1 type A receptor antibodies on the outcome of
      liver retransplantation.

      The goal of these observational study is to perfect donor-recipient matching to attain the
      best outcome. In addition, we may develop hypotheses and potential treatments that would be
      tested in further clinical trials.
observational model: Cohort
time perspective: Retrospective
measure: Retransplant graft survival
time frame: From date of transplantation until the date of next transplantation or date of death from any cause, whichever came first, assessed up to 240 months
description: Average length of time the second liver graft remains in a living recipient regardless of function
measure: Patient survival
time frame: From date of transplantation until the date of death from any cause assessed up to 240 months
description: Average length of time a recipient is alive regardless of presence of the second liver transplant
measure: Acute rejection
time frame: From date of transplantation until the date of first documented acute rejection assessed up to 240 months
description: number of participants with a clinically diagnosed and treated episode of rejection (either acute cellular or humoral)
arm group label: D2SA+
description: Median fluoresce intensity > or = 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
arm group label: D2SA-
description: Median fluoresce intensity < 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
intervention type: Diagnostic Test
intervention name: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
description: Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)
arm group label: D2SA+
arm group label: D2SA-
other name: AT1R antibody
Blood and tissue samples stored for clinical use by the Transplant Laboratory since the
      beginning of liver transplantation at our facility in 1977
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Vivian McAlister
role: Principal Investigator
affiliation: London Health Sciences Center
responsible party type: Principal Investigator
investigator affiliation: London Health Sciences Centre
investigator full name: Vivian McAlister
investigator title: Professor of Surgery
mesh term: Antibodies
mesh term: Immunoglobulins
sharing ipd: Yes
ipd description: Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: From publication until 5 years later
ipd access criteria: De-identified subject level data will be shared with researchers who contact the principal investigator, submit a research plan and sign an agreement. Approval by Western Research Ethics may be required depending on the request.
submitted: April 4, 2022
returned: October 18, 2022
submitted: October 18, 2022
returned: August 29, 2023