Genomics of Kidney Transplantation

This study is currently recruiting participants.
Verified October 2012 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01714440
First received: October 17, 2012
Last updated: November 5, 2013
Last verified: October 2012
  Purpose

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.

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 Transplantation

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective

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 ]
  • 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 Genotype: 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 Genotype: 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).

  • For 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.

  • 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 ]

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 ]

Estimated Enrollment: 4300
Study Start Date: August 2012
Groups/Cohorts
Kidney and Kidney-Pancreas Transplant Recipients
Transplant Donors
Activity and mRNA Expression
The Activity and mRNA Expression Cohort is a substudy cohort, and also 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 the required sample size of 600 is achieved or the protocol team terminates enrollment of the cohort. 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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.
  • 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 Study.
  • Informed consent for participation in the Activity and mRNA Expression Cohort.
  • Age 18 years or greater as of day of transplantation.
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01714440

Contacts
Contact: A Matas, MD 612-625-6460 matas001@umn.edu

Locations
United States, Alabama
University of Alabama Not yet recruiting
Birmingham, Alabama, United States
Contact: Tina Ayer    205-996-2577    tayer@uab.edu   
Contact: Tena Hilario    205-996-7733    tena@uab.edu   
Principal Investigator: R. Mannon, MD         
Sub-Investigator: R. Gaston, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55414
Contact: Mandi DeGrote    612-625-1172    carl1032@umn.edu   
Contact: Danielle Berglund    612-624-0427    bergl175@umn.edu   
Principal Investigator: Arthur Matas, MD         
Hennepin County Medical Center Recruiting
Minneapolis, Minnesota, United States, 55415
Contact: Lisa Berndt    612-347-5871      
Principal Investigator: Bertram Kasiske, MD         
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Thomas DeLeeuw    507-538-8764      
Principal Investigator: F. G. Cosio, MD         
Canada, Alberta
University of Alberta Not yet recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Susan Huygen       Susan.Huygen@albertahealthservices.ca   
Contact: Sergey Nikitin       Sergey.Nikitin@albertahealthservices.ca   
Principal Investigator: Sita Gourishankar, MD         
Sponsors and Collaborators
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

No publications provided

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: November 5, 2013
Health Authority: United States: Federal Government

ClinicalTrials.gov processed this record on April 15, 2014