Genomics of Kidney Transplantation

Completed

• Conditions: Kidney Transplant Donor; KidneyTransplant Recipients; Simultaneous Kidney/Pancreas Recipients

• Registration Number: NCT01714440
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

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.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-10-17
• Study First Submitted QC: 2012-10-25
• Study First Posted: 2012-10-26
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-02
• Last Update Posted: 2017-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1552

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)	Day 0 to Year 5	eGFR: Estimated GFR test results are a measure of kidney function.
Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities	Day 0 to Year 5	Toxicities may include: new onset diabetes or nephrotoxicity. CNI: calcineurin inhibitor
Transplant recipient genotypes: time to acute rejection	Day 0 to Year 5
Transplant recipient genotypes: time to allograft failure	Day 0 to Year 5	allograft failure is defined as graft loss or participant death.
Donor Genotypes: time to a persistent 25% decrease in eGFR	Day 0 to year 5	The time to a persistent 25% decrease in eGFR in the donated organ's recipient.
Donor Genotypes: time to chronic graft dysfunction	Day 0 to Year 5	The time to dysfunction of the donated organ.
Donor Genotypes: time to allograft failure	Day 0 to Year 5	The time to the failure of the donated organ (defined as graft loss or participant death).
Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression	Day 0 to Year 5	CN: Calcineurin. IMPDH: Inosine-5'-monophosphate dehydrogenase
Transplant recipient genotypes: time to chronic graft disfunction	Day 0 to Year 5
Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels	Day 0 to Year 5
Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)	Day 0 to Year 5

Secondary Outcome Measures

Name	Time	Method
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	Day 0 to Year 5
Slope of eGFR	Day 0 to Year 5
Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine	Day 0 to Year 5
Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection	Day 0 to Year 5	EBV: Epstein-Barr virus. CMV: cytomegalovirus.
Delayed graft function	Day 0 to Year 5

Trial Locations

Locations (5)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States