Genomics of Kidney Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genomics of Transplantation Cooperative Research Program
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01714440
First received: October 17, 2012
Last updated: July 15, 2016
Last verified: July 2016
  Purpose
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.

Condition
Kidney (or Simultaneous Kidney-Pancreas) Transplant Recipients
Kidney Transplant Donor

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genomics of Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Transplant recipient genotypes: time to chronic graft disfunction [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Transplant recipient genotypes: time to a persistent 25% decrease in eGFR [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
    eGFR: Estimated GFR test results are a measure of kidney function.

  • Transplant recipient genotypes: time to acute rejection [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Transplant recipient genotypes: time to allograft failure [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
    allograft failure is defined as graft loss or participant death.

  • Donor Genotypes: time to chronic graft dysfunction [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: No ]
    The time to dysfunction of the donated organ.

  • Donor Genotypes: time to a persistent 25% decrease in eGFR [ Time Frame: Day 0 to year 5 ] [ Designated as safety issue: No ]
    The time to a persistent 25% decrease in eGFR in the donated organ's recipient.

  • Donor Genotypes: time to allograft failure [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: No ]
    The time to the failure of the donated organ (defined as graft loss or participant death).

  • Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia) [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Recipient genotypes: time to select CNI-related toxicities [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
    Toxicities may include: new onset diabetes or nephrotoxicity. CNI: calcineurin inhibitor

  • Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: No ]
  • Recipient candidate genotypes: CN and IMPDH protein activity and expression [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: No ]
    CN: Calcineurin. IMPDH: Inosine-5'-monophosphate dehydrogenase


Secondary Outcome Measures:
  • Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Time to renal biopsy with presence of the following semi-quantitative pathology endpoints: patterns of Banff biopsy score, presence of circulating anti-donor anti-HLA antibodies, C4d positivity [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Slope of eGFR [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: No ]
  • Delayed graft function [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
  • Time to EBV and CMV infection [ Time Frame: Day 0 to Year 5 ] [ Designated as safety issue: Yes ]
    EBV: Epstein-Barr virus. CMV: cytomegalovirus.


Biospecimen Retention:   Samples With DNA
Whole blood

Enrollment: 1552
Study Start Date: August 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Transplant Recipients Cohort
Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients. Enrollment for this cohort is closed.
Transplant Donors Cohort
Main Study Cohort: The kidney donor for transplant recipients in this study. Enrollment for this cohort is closed.
Activity&mRNA Expression Substudy Cohort

**Enrollment for this subset of subjects already enrolled in the Main Study remains open at specific sites.

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 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.


Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors
Criteria

Inclusion Criteria:

  • Kidney (or kidney-pancreas) transplant recipient no more than 10 days post-transplant or kidney donor no more than 30 days post-transplant or previously enrolled in Phase I of the Genomics of Kidney Transplantation Study;
  • No organs other than kidney or pancreas transplanted simultaneously with the qualifying kidney transplant; and
  • Participant or parent/guardian must be able to understand and provide written informed consent.

Inclusion for the Activity and mRNA Expression Cohort:

  • Recipient enrolled in the Main Cohort Study;
  • Informed consent for participation in the Activity and mRNA Expression Cohort;
  • Age 18 years or greater as of day of transplantation;and
  • Will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance immunosuppression therapy.

Exclusion Criteria:

- Inability or unwillingness of the participant or parent/guardian to give a written informed consent or comply with the study protocol.

For the Activity and mRNA Expression Cohort:

- Inability or unwillingness of the participant or parent/guardian to give a written informed consent for participation in the Activity and mRNA Expression Cohort or comply with the study protocol.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714440

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55414
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
Mayo Clinic
Rochester, Minnesota, United States, 55905
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2B7
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Genomics of Transplantation Cooperative Research Program
Investigators
Principal Investigator: A Matas, MD University of Minnesota - Clinical and Translational Science Institute
Study Chair: A Israni, MD, MS University of Minnesota - Clinical and Translational Science Institute
  More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01714440     History of Changes
Other Study ID Numbers: DAIT GEN-03 
Study First Received: October 17, 2012
Last Updated: July 15, 2016
Health Authority: United States: Federal Government
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
genomics of kidney transplantation
genetic variation
recipient genotypes
donor genotypes

ClinicalTrials.gov processed this record on July 21, 2016