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Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level (ACORG-HLA)

26 de abril de 2019 actualizado por: Assistance Publique - Hôpitaux de Paris

Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level: a Track to Improve Organ Allocation

Transplantation is the only treatment for end-stage organ dysfunction, with dialysis for the kidney. However, donor / recipient (D / R) tissue incompatibility accounts for the majority of long-term graft losses, through the development of serum-specific donor antibodies (DSA) to human leukocyte antigens (HLA) of donor, with a prevalence of about 10% at 2 years and 20% at 5 years.

DSA immunization is very often directed against one or a few of the donor's incompatible antigens, suggesting that epitopes (and antigens) are not all equally immunogenic. Identifying HLA epitopes that cause the most and the least immunization would help refine the graft distribution to better manage a limited resource by defining the D / R combinations to avoid or promote. Since the immunogenicity of an HLA epitope depends on the HLA of the recipient given the properties of the epitopes mentioned above, a very large cohort is needed to understand this question. To do so, it is necessary to redo these typings with a method exploring all the genes (add DQA1, DRB3 / 4/5, DPB1 and DPA1) when this has not been done after the graft as part of the standard care. This has become possible since 3 years by DNA sequencing called "new generation" (or NGS), a method that is supplanting all others for the medical care of patients in transplantation.

This study is a retrospective cohort study with 5-year follow-up. The investigators' main objective is to evaluate the predictive value of the number of mismatched HLA epitopes for the development of DSA anti-HLA de novo at 2 years. The investigators' secondary objectives are to evaluate this parameter at 5 and 8 years to determine which epitope mismatches should be favored / avoided in the future.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Tipo de estudio

De observación

Inscripción (Anticipado)

20000

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.

Estudio Contacto

Copia de seguridad de contactos de estudio

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

7 años y mayores (Niño, Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra no probabilística

Población de estudio

Patients (adults and children) récipients of a first kidney transplant / heart / lung / liver donor living or deceased,non-immunized anti-HLA before the transplant, having preserved their graft > 2 years will be enrolled

Descripción

Inclusion Criteria:

  • patients (adults and children)
  • patients recipients in France from 2008 to 2015 of a first kidney transplant / heart / lung / liver donor living or deceased, non-immunized anti-HLA before the transplant
  • patients having preserved their graft > 2 years
  • having agreed to the use for research purposes in transplantation of the remains of the DNA and serum samples taken as part of the care of which the remains are available

Exclusion Criteria:

  • no inclusion if one of the inclusion criteria is not met

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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Proportion of serum-specific donor antibodies (DSA)
Periodo de tiempo: at 2 years after organ transplantation
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
at 2 years after organ transplantation

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Proportion of dnDSA anti-HLA
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of dnDSA anti-HLA
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of dnDSA anti-HLA
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
Periodo de tiempo: at 2 years after organ transplantation
at 2 years after organ transplantation
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Survival of the graft
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Survival of the graft
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation
Overall survival
Periodo de tiempo: at 5 years after organ transplantation
at 5 years after organ transplantation
Overall survival
Periodo de tiempo: at 8 years after organ transplantation
at 8 years after organ transplantation

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

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 (Anticipado)

1 de mayo de 2019

Finalización primaria (Anticipado)

1 de mayo de 2019

Finalización del estudio (Anticipado)

1 de mayo de 2025

Fechas de registro del estudio

Enviado por primera vez

1 de marzo de 2019

Primero enviado que cumplió con los criterios de control de calidad

4 de marzo de 2019

Publicado por primera vez (Actual)

5 de marzo de 2019

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

29 de abril de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

26 de abril de 2019

Última verificación

1 de febrero de 2019

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • NI16035HLJ

Plan de datos de participantes individuales (IPD)

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INDECISO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

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. .

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