Genomics of Kidney Transplantation
2 juni 2017 uppdaterad av: National Institute of Allergy and Infectious Diseases (NIAID)
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.
Studieöversikt
Status
Avslutad
Detaljerad beskrivning
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.
Studietyp
Observationell
Inskrivning (Faktisk)
1552
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Alabama
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Birmingham, Alabama, Förenta staterna, 35294
- University of Alabama
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55415
- Hennepin County Medical Center
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Minneapolis, Minnesota, Förenta staterna, 55414
- University of Minnesota
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Rochester, Minnesota, Förenta staterna, 55905
- Mayo Clinic
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Alberta
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Edmonton, Alberta, Kanada, T6G 2B7
- University of Alberta
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Barn
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Testmetod
Icke-sannolikhetsprov
Studera befolkning
Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
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Transplant Recipients Cohort
Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients.
Enrollment for this cohort is closed.
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Transplant Donors Cohort
Main Study Cohort: The kidney donor for transplant recipients in this study.
Enrollment for this cohort is closed.
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Activity&mRNA Expression Substudy Cohort
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.
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Transplant recipient genotypes: time to chronic graft disfunction
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)
Tidsram: Day 0 to Year 5
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eGFR: Estimated GFR test results are a measure of kidney function.
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Day 0 to Year 5
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Transplant recipient genotypes: time to acute rejection
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Transplant recipient genotypes: time to allograft failure
Tidsram: Day 0 to Year 5
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allograft failure is defined as graft loss or participant death.
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Day 0 to Year 5
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Donor Genotypes: time to chronic graft dysfunction
Tidsram: Day 0 to Year 5
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The time to dysfunction of the donated organ.
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Day 0 to Year 5
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Donor Genotypes: time to a persistent 25% decrease in eGFR
Tidsram: Day 0 to year 5
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The time to a persistent 25% decrease in eGFR in the donated organ's recipient.
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Day 0 to year 5
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Donor Genotypes: time to allograft failure
Tidsram: Day 0 to Year 5
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The time to the failure of the donated organ (defined as graft loss or participant death).
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Day 0 to Year 5
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Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities
Tidsram: Day 0 to Year 5
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Toxicities may include: new onset diabetes or nephrotoxicity.
CNI: calcineurin inhibitor
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Day 0 to Year 5
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Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression
Tidsram: Day 0 to Year 5
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CN: Calcineurin.
IMPDH: Inosine-5'-monophosphate dehydrogenase
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Day 0 to Year 5
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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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
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Slope of eGFR
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Delayed graft function
Tidsram: Day 0 to Year 5
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Day 0 to Year 5
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Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection
Tidsram: Day 0 to Year 5
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EBV: Epstein-Barr virus.
CMV: cytomegalovirus.
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Day 0 to Year 5
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Samarbetspartners
Utredare
- Huvudutredare: A Matas, MD, University of Minnesota
- Studiestol: A Israni, MD, MS, University of Minnesota
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Oetting WS, Schladt DP, Dorr CR, Wu B, Guan W, Remmel RP, Ikle D, Mannon RB, Matas AJ, Israni AK, Jacobson PA; DeKAF Genomics and GEN03 Investigators. Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients: Validation of rs2910164 in MicroRNA MIR146A. Transplantation. 2019 Aug;103(8):1591-1602. doi: 10.1097/TP.0000000000002659.
- Nguyen TT, Pearson RA, Mohamed ME, Schladt DP, Berglund D, Rivers Z, Skaar DJ, Wu B, Guan W, van Setten J, Keating BJ, Dorr C, Remmel RP, Matas AJ, Mannon RB, Israni AK, Oetting WS, Jacobson PA. Pharmacogenomics in kidney transplant recipients and potential for integration into practice. J Clin Pharm Ther. 2020 Dec;45(6):1457-1465. doi: 10.1111/jcpt.13223. Epub 2020 Jul 14.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 augusti 2012
Primärt slutförande (Faktisk)
1 januari 2017
Avslutad studie (Faktisk)
1 januari 2017
Studieregistreringsdatum
Först inskickad
17 oktober 2012
Först inskickad som uppfyllde QC-kriterierna
25 oktober 2012
Första postat (Uppskatta)
26 oktober 2012
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
5 juni 2017
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
2 juni 2017
Senast verifierad
1 juni 2017
Mer information
Termer relaterade till denna studie
Andra studie-ID-nummer
- DAIT GEN-03
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