<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/NCT01714440</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT GEN-03</org_study_id>
    <nct_id>NCT01714440</nct_id>
  </id_info>
  <brief_title>Genomics of Kidney Transplantation</brief_title>
  <official_title>Genomics of Kidney Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genomics of Transplantation Cooperative Research Program</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The major aim of this research study is to investigate the relationship between genetic&#xD;
      variation in DNA (inherited code material in the cells of the body) and factors affecting&#xD;
      transplant outcomes, like the drugs people receive or the way their immune systems work, for&#xD;
      example. To do this, investigators will collect blood samples from participants. Genetic&#xD;
      material will be separated from each blood sample and analyzed, looking for genetic&#xD;
      variation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the past, the major problems in kidney transplantation were surgical complications, acute&#xD;
      rejection, and infections. Right now, researchers are focusing on improving immune&#xD;
      suppression therapy and achieving better long-term survival of kidney transplants. One of the&#xD;
      ways to try to understand what causes loss of function after many years is to find out if&#xD;
      there is a genetic factor involved.&#xD;
&#xD;
      There are a number of differences in specific genes that have been identified and are thought&#xD;
      to affect transplant outcomes. Studying these gene variations (differences between people or&#xD;
      differences between populations) is important in determining whether these variations are&#xD;
      related to transplant outcomes and how this information can help patients achieve better&#xD;
      long-term transplant survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>Transplant recipient genotypes: time to chronic graft disfunction</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>eGFR: Estimated GFR test results are a measure of kidney function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Transplant recipient genotypes: time to acute rejection</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Transplant recipient genotypes: time to allograft failure</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>allograft failure is defined as graft loss or participant death.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Donor Genotypes: time to chronic graft dysfunction</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>The time to dysfunction of the donated organ.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Donor Genotypes: time to a persistent 25% decrease in eGFR</measure>
    <time_frame>Day 0 to year 5</time_frame>
    <description>The time to a persistent 25% decrease in eGFR in the donated organ's recipient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Donor Genotypes: time to allograft failure</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>The time to the failure of the donated organ (defined as graft loss or participant death).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>Toxicities may include: new onset diabetes or nephrotoxicity. CNI: calcineurin inhibitor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>CN: Calcineurin. IMPDH: Inosine-5'-monophosphate dehydrogenase</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to renal biopsy with presence of the following semi-quantitative pathology endpoints: patterns of Banff biopsy score, presence of circulating anti-donor anti-Human Leukocyte Antigen (HLA) antibodies, C4d positivity</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Slope of eGFR</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delayed graft function</measure>
    <time_frame>Day 0 to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection</measure>
    <time_frame>Day 0 to Year 5</time_frame>
    <description>EBV: Epstein-Barr virus. CMV: cytomegalovirus.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">1552</enrollment>
  <condition>KidneyTransplant Recipients</condition>
  <condition>Simultaneous Kidney/Pancreas Recipients</condition>
  <condition>Kidney Transplant Donor</condition>
  <arm_group>
    <arm_group_label>Transplant Recipients Cohort</arm_group_label>
    <description>Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients. Enrollment for this cohort is closed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Transplant Donors Cohort</arm_group_label>
    <description>Main Study Cohort: The kidney donor for transplant recipients in this study. Enrollment for this cohort is closed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Activity&amp;mRNA Expression Substudy Cohort</arm_group_label>
    <description>A subset of subjects enrolled in the main study who will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance immunosuppression therapy. This group has a prospective observational cohort design. Enrollment into the Activity and messenger ribonucleic acid (mRNA) Expression Cohort, occurring concurrently with enrollment of the rest of the study, will continue until either the required sample size of 600 is achieved or the protocol team terminates enrollment. Participants in the Activity and mRNA Expression Cohort have additional blood draws up to 2 weeks prior to transplant, at week 1, Month 3 and Month 6 post-transplant.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Kidney (or kidney-pancreas) transplant recipient no more than 10 days post-transplant&#xD;
             or kidney donor no more than 30 days post-transplant or previously enrolled in Phase I&#xD;
             of the Genomics of Kidney Transplantation Study;&#xD;
&#xD;
          -  No organs other than kidney or pancreas transplanted simultaneously with the&#xD;
             qualifying kidney transplant; and&#xD;
&#xD;
          -  Participant or parent/guardian must be able to understand and provide written informed&#xD;
             consent.&#xD;
&#xD;
        Inclusion for the Activity and mRNA Expression Cohort:&#xD;
&#xD;
          -  Recipient enrolled in the Main Cohort Study;&#xD;
&#xD;
          -  Informed consent for participation in the Activity and mRNA Expression Cohort;&#xD;
&#xD;
          -  Age 18 years or greater as of day of transplantation;and&#xD;
&#xD;
          -  Will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance&#xD;
             immunosuppression therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Inability or unwillingness of the participant or parent/guardian to give a written&#xD;
        informed consent or comply with the study protocol.&#xD;
&#xD;
        For the Activity and mRNA Expression Cohort:&#xD;
&#xD;
        - Inability or unwillingness of the participant or parent/guardian to give a written&#xD;
        informed consent for participation in the Activity and mRNA Expression Cohort or comply&#xD;
        with the study protocol.&#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>A Matas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>A Israni, MD, MS</last_name>
    <role>Study Chair</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.niaid.nih.gov/</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID) website</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/about/dait</url>
    <description>Division of Allergy, Immunology, and Transplantation (DAIT) website</description>
  </link>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 17, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <last_update_submitted>June 2, 2017</last_update_submitted>
  <last_update_submitted_qc>June 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>genomics of kidney transplantation</keyword>
  <keyword>genetic variation</keyword>
  <keyword>recipient genotypes</keyword>
  <keyword>donor genotypes</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/NCT01714440
org study id: DAIT GEN-03
nct id: NCT01714440
lead sponsor: 
collaborator: 
has dmc: Yes
The major aim of this research study is to investigate the relationship between genetic
      variation in DNA (inherited code material in the cells of the body) and factors affecting
      transplant outcomes, like the drugs people receive or the way their immune systems work, for
      example. To do this, investigators will collect blood samples from participants. Genetic
      material will be separated from each blood sample and analyzed, looking for genetic
      variation.
In the past, the major problems in kidney transplantation were surgical complications, acute
      rejection, and infections. Right now, researchers are focusing on improving immune
      suppression therapy and achieving better long-term survival of kidney transplants. One of the
      ways to try to understand what causes loss of function after many years is to find out if
      there is a genetic factor involved.

      There are a number of differences in specific genes that have been identified and are thought
      to affect transplant outcomes. Studying these gene variations (differences between people or
      differences between populations) is important in determining whether these variations are
      related to transplant outcomes and how this information can help patients achieve better
      long-term transplant survival.
observational model: Cohort
time perspective: Prospective
measure: Transplant recipient genotypes: time to chronic graft disfunction
time frame: Day 0 to Year 5
measure: Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)
time frame: Day 0 to Year 5
description: eGFR: Estimated GFR test results are a measure of kidney function.
measure: Transplant recipient genotypes: time to acute rejection
time frame: Day 0 to Year 5
measure: Transplant recipient genotypes: time to allograft failure
time frame: Day 0 to Year 5
description: allograft failure is defined as graft loss or participant death.
measure: Donor Genotypes: time to chronic graft dysfunction
time frame: Day 0 to Year 5
description: The time to dysfunction of the donated organ.
measure: Donor Genotypes: time to a persistent 25% decrease in eGFR
time frame: Day 0 to year 5
description: The time to a persistent 25% decrease in eGFR in the donated organ's recipient.
measure: Donor Genotypes: time to allograft failure
time frame: Day 0 to Year 5
description: The time to the failure of the donated organ (defined as graft loss or participant death).
measure: Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)
time frame: Day 0 to Year 5
measure: Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities
time frame: Day 0 to Year 5
description: Toxicities may include: new onset diabetes or nephrotoxicity. CNI: calcineurin inhibitor
measure: Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels
time frame: Day 0 to Year 5
measure: Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression
time frame: Day 0 to Year 5
description: CN: Calcineurin. IMPDH: Inosine-5'-monophosphate dehydrogenase
measure: Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine
time frame: Day 0 to Year 5
measure: Time to renal biopsy with presence of the following semi-quantitative pathology endpoints: patterns of Banff biopsy score, presence of circulating anti-donor anti-Human Leukocyte Antigen (HLA) antibodies, C4d positivity
time frame: Day 0 to Year 5
measure: Slope of eGFR
time frame: Day 0 to Year 5
measure: Delayed graft function
time frame: Day 0 to Year 5
measure: Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection
time frame: Day 0 to Year 5
description: EBV: Epstein-Barr virus. CMV: cytomegalovirus.
arm group label: Transplant Recipients Cohort
description: Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients. Enrollment for this cohort is closed.
arm group label: Transplant Donors Cohort
description: Main Study Cohort: The kidney donor for transplant recipients in this study. Enrollment for this cohort is closed.
arm group label: Activity&mRNA Expression Substudy Cohort
description: A subset of subjects enrolled in the main study who will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance immunosuppression therapy. This group has a prospective observational cohort design. Enrollment into the Activity and messenger ribonucleic acid (mRNA) Expression Cohort, occurring concurrently with enrollment of the rest of the study, will continue until either the required sample size of 600 is achieved or the protocol team terminates enrollment. Participants in the Activity and mRNA Expression Cohort have additional blood draws up to 2 weeks prior to transplant, at week 1, Month 3 and Month 6 post-transplant.
Whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: A Matas, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: A Israni, MD, MS
role: Study Chair
affiliation: University of Minnesota
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
url: https://www.niaid.nih.gov/
description: National Institute of Allergy and Infectious Diseases (NIAID) website
url: https://www.niaid.nih.gov/about/dait
description: Division of Allergy, Immunology, and Transplantation (DAIT) website
responsible party type: Sponsor