Genomics of Kidney Transplantation
2 de junio de 2017 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Descripción detallada
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.
Tipo de estudio
De observación
Inscripción (Actual)
1552
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
Alberta
-
Edmonton, Alberta, Canadá, T6G 2B7
- University of Alberta
-
-
-
-
Alabama
-
Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama
-
-
Minnesota
-
Minneapolis, Minnesota, Estados Unidos, 55415
- Hennepin County Medical Center
-
Minneapolis, Minnesota, Estados Unidos, 55414
- University of Minnesota
-
Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
|
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
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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Transplant recipient genotypes: time to chronic graft disfunction
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)
Periodo de tiempo: Day 0 to Year 5
|
eGFR: Estimated GFR test results are a measure of kidney function.
|
Day 0 to Year 5
|
|
Transplant recipient genotypes: time to acute rejection
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Transplant recipient genotypes: time to allograft failure
Periodo de tiempo: Day 0 to Year 5
|
allograft failure is defined as graft loss or participant death.
|
Day 0 to Year 5
|
|
Donor Genotypes: time to chronic graft dysfunction
Periodo de tiempo: Day 0 to Year 5
|
The time to dysfunction of the donated organ.
|
Day 0 to Year 5
|
|
Donor Genotypes: time to a persistent 25% decrease in eGFR
Periodo de tiempo: Day 0 to year 5
|
The time to a persistent 25% decrease in eGFR in the donated organ's recipient.
|
Day 0 to year 5
|
|
Donor Genotypes: time to allograft failure
Periodo de tiempo: Day 0 to Year 5
|
The time to the failure of the donated organ (defined as graft loss or participant death).
|
Day 0 to Year 5
|
|
Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities
Periodo de tiempo: Day 0 to Year 5
|
Toxicities may include: new onset diabetes or nephrotoxicity.
CNI: calcineurin inhibitor
|
Day 0 to Year 5
|
|
Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression
Periodo de tiempo: Day 0 to Year 5
|
CN: Calcineurin.
IMPDH: Inosine-5'-monophosphate dehydrogenase
|
Day 0 to Year 5
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
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
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Slope of eGFR
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Delayed graft function
Periodo de tiempo: Day 0 to Year 5
|
Day 0 to Year 5
|
|
|
Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection
Periodo de tiempo: Day 0 to Year 5
|
EBV: Epstein-Barr virus.
CMV: cytomegalovirus.
|
Day 0 to Year 5
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Colaboradores
Investigadores
- Investigador principal: A Matas, MD, University of Minnesota
- Silla de estudio: A Israni, MD, MS, University of Minnesota
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de agosto de 2012
Finalización primaria (Actual)
1 de enero de 2017
Finalización del estudio (Actual)
1 de enero de 2017
Fechas de registro del estudio
Enviado por primera vez
17 de octubre de 2012
Primero enviado que cumplió con los criterios de control de calidad
25 de octubre de 2012
Publicado por primera vez (Estimar)
26 de octubre de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de junio de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
2 de junio de 2017
Última verificación
1 de junio de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- DAIT GEN-03
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .