Genomics of Kidney Transplantation
2. juni 2017 oppdatert 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.
Studieoversikt
Status
Fullført
Detaljert beskrivelse
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.
Studietype
Observasjonsmessig
Registrering (Faktiske)
1552
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta
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Alabama
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Birmingham, Alabama, Forente stater, 35294
- University Of Alabama
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Minnesota
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Minneapolis, Minnesota, Forente stater, 55415
- Hennepin County Medical Center
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Minneapolis, Minnesota, Forente stater, 55414
- University of Minnesota
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Rochester, Minnesota, Forente stater, 55905
- Mayo Clinic
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors
Beskrivelse
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / 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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Transplant recipient genotypes: time to chronic graft disfunction
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine
Tidsramme: 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
Tidsramme: Day 0 to Year 5
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Day 0 to Year 5
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Slope of eGFR
Tidsramme: Day 0 to Year 5
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Day 0 to Year 5
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Delayed graft function
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: A Matas, MD, University of Minnesota
- Studiestol: A Israni, MD, MS, University of Minnesota
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. august 2012
Primær fullføring (Faktiske)
1. januar 2017
Studiet fullført (Faktiske)
1. januar 2017
Datoer for studieregistrering
Først innsendt
17. oktober 2012
Først innsendt som oppfylte QC-kriteriene
25. oktober 2012
Først lagt ut (Anslag)
26. oktober 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
5. juni 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
2. juni 2017
Sist bekreftet
1. juni 2017
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- DAIT GEN-03
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