Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

Neurogenetics and Multi-omics of Neuroinflammatory Diseases in Multiplex Families to Improve Patients Health (NeuroDIP)

2 de noviembre de 2026 actualizado por: Institut National de la Santé Et de la Recherche Médicale, France

The goal of this observational study is to learn why some families have several members with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or MOG antibody-associated disease (MOGAD). These diseases happen when the immune system attacks the brain, optic nerves, or spinal cord. The study includes about 500 people from about 100 families: people with one of these diseases and their relatives who do not have it. The main question is: Do rare gene changes (variants) shared by family members explain why these diseases run in families? Researchers will compare the DNA of family members who have the disease with the DNA of relatives who do not. They will also look at how genes are switched on and off in blood cells. Participants will:

  • Attend one visit of 2 to 3 hours at one of five French hospitals
  • Answer questions about their health, treatments, and family history
  • Give a 50 mL blood sample

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

Background: Large genetic studies have found many common gene variants that raise the risk of multiple sclerosis, but they explain only part of the inherited risk. They also explain familial forms poorly. Rare variants with a strong effect may be shared within a family and go unnoticed in studies of unrelated people. Families with several affected members are well suited to finding them. NeuroDIP combines genetic, epigenetic (DNA methylation), and gene expression data from these families and links them to clinical information.

Design: This is a cross-sectional, family-based study with a single visit and no follow-up. Comparing affected members with unaffected relatives from the same family helps limit the effect of ancestry and of factors that relatives share.

Visit: At the hospital, participants give written consent and have a short physical examination. Patients also have a disability assessment (EDSS). The investigator draws a family tree and records medical history, treatments, lifestyle, and any previous brain MRI report. A blood sample is then drawn. The study does not change usual medical care. Relatives are invited through the affected family member and are contacted by the investigating centre.

Samples and data: Samples and data carry a code, and names are kept only at the investigating centre. Samples are processed and stored in accredited biological resource centres. Research data are stored on secure servers in France and are not transferred outside the European Union. With participants' consent, coded data and samples may be used in future research on neuroinflammatory diseases, including deposit in the French MS registry (OFSEP).

Results: Participants do not receive individual research results. The exception is an incidental finding with health consequences, and participants must agree to be informed of such a finding before they take part. Participants can ask for the overall results and may be invited to an optional information meeting for families.

Funding: The study is funded by the Inserm Messidore 2024 call and by the ARSEP Foundation, and belongs to the NeuroDINet network on neuroinflammatory diseases.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

500

Fase

  • No aplica

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

Ubicaciones de estudio

  • Francia
      • Bron, Francia, 69500
        • Hospice Civil de Lyon - Hospital Pierre Wertheimer
        • Contacto:
        • Investigador principal:
          • Sandra Vukusic
      • Nantes, Francia, 44000
        • University Hospital Laennec
        • Investigador principal:
          • David-Axel LAPLAUD
        • Contacto:
      • Nice, Francia, 06002
        • University Hospital Pasteur 2
        • Investigador principal:
          • Christine LEBRUN-FRENAY
        • Contacto:
      • Paris, Francia, 75013
        • Assistance Publique Hôpitaux de Paris- La Pitié Salpêtrière Hospital
        • Contacto:
        • Investigador principal:
          • Céline LOUAPRE
      • Rennes, Francia, 35000
        • University Hospital Pontchaillou
        • Investigador principal:
          • Laure MICHEL
        • Contacto:

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

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

Acepta Voluntarios Saludables

Sí

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Affected participants:

    • Age 15 years and 3 months or older
    • Multiple sclerosis (2024 McDonald criteria), neuromyelitis optica spectrum disorder with anti-AQP4 antibodies (2015 Wingerchuk criteria), or MOG antibody-associated disease (2023 international MOGAD panel criteria)
    • Member of a multiplex family: at least two affected members sharing at least 12.5% of their genetic heritage
    • Affiliated to a social security scheme or equivalent
    • Written informed consent (for minors: assent of the minor and consent of the holders of parental authority)

  • Unaffected relatives:

    • Age 18 years or older
    • Sharing at least 25% of genetic heritage with one of the two affected family members
    • No multiple sclerosis, NMOSD, MOGAD, or other known inflammatory disease of the central nervous system
    • Affiliated to a social security scheme or equivalent
    • Written informed consent

  • Transcriptomic sub-cohort (30 to 60 participants, about 10 families):

    • Patients with no immunomodulatory or immunosuppressive treatment for at least 12 months, and their relatives

Exclusion Criteria:

  • Refusal to participate before the inclusion visit
  • Inability to understand the study information or to consent
  • Person under guardianship, curatorship or legal protection
  • Person deprived of liberty by judicial or administrative decision
  • Pregnant or breastfeeding woman
  • No kinship with at least one affected member of the included family
  • Refusal to be informed of an incidental discovery of a pathogenic genetic variant

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

  • Propósito principal: Ciencia básica
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Otro: Multiplex family members (patients and relatives)

Four participant categories (people with MS, NMOSD, MOGAD, and healthy) with their approximate numbers.
Prueba de diagnóstico: Blood sampling and multi-omic profiling

One venous blood sample (50 mL) is drawn at a single visit. DNA is used for whole-genome sequencing. Cryopreserved peripheral blood mononuclear cells (PBMCs) are used for DNA methylation profiling and RNA sequencing. Serum is used to measure GFAP and NfL.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Rare high-penetrance variants co-segregating with disease within multiplex families.
Periodo de tiempo: 36 months from the first inclusion.

Proportion of rare (minor allele frequency < 1%), high-penetrance variants found in affected members and absent or significantly less frequent in unaffected relatives of the same family sharing at least 25% of their genetic heritage. Assessed by co-segregation and linkage analysis, family-based association tests and in silico prediction of variant impact.
36 months from the first inclusion.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
eQTL: genetic loci associated with gene expression in PBMC
Periodo de tiempo: 36 months from the first inclusion.

Loci where genetic variants are associated with differences in gene expression in peripheral blood mononuclear cells (PBMC), from integrated whole genome sequencing and RNA sequencing data, in the untreated patient sub-group and their relatives.
36 months from the first inclusion.
Disease-associated DNA methylation (CpG sites)
Periodo de tiempo: 36 months from the first inclusion.

Number and type of CpG sites differentially methylated between patients and unaffected relatives, measured with EPIC arrays on PBMC DNA, in the untreated patient sub-group and their relatives.
36 months from the first inclusion.
Transcriptomic signatures of PBMC subpopulations
Periodo de tiempo: 36 months from the first inclusion.

Differentially expressed genes and perturbed pathways in immune cell subpopulations, from bulk and single-cell RNA sequencing of PBMC, comparing untreated patients (dedicated sub-cohort, n = 30 to 60) with their unaffected relatives.
36 months from the first inclusion.
Multi-omic molecular signatures
Periodo de tiempo: 36 months from the first inclusion.

Molecular signatures obtained by integrating genomic, DNA methylation and transcriptomic data (omicsNPC framework, multilevel modelling), used to model familial risk.
36 months from the first inclusion.
Evaluation of the correlation with the disease phenotype
Periodo de tiempo: 36 months from the first inclusion.

A potential correlation will be evaluated between genetic variants, DNA methylation, gene expression profiles and clinical data (age at onset , disease course, treatment response ) of patient.
36 months from the first inclusion.

Colaboradores e Investigadores

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

Patrocinador

Institut National de la Santé Et de la Recherche Médicale, France

Colaboradores

Nantes University Hospital
Université de Nantes
Fondation ARSEP

Investigadores

  • Investigador principal: Nicolas VINCE, PhD, Nantes Université

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

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 (Estimado)

1 de noviembre de 2026

Finalización primaria (Estimado)

1 de abril de 2029

Finalización del estudio (Estimado)

1 de octubre de 2029

Fechas de registro del estudio

Enviado por primera vez

13 de octubre de 2026

Primero enviado que cumplió con los criterios de control de calidad

22 de octubre de 2026

Publicado por primera vez (Actual)

28 de octubre de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

4 de noviembre de 2026

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

2 de noviembre de 2026

Última verificación

1 de noviembre de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • C25-79
  • 2026-A01125-46 (Identificador de registro: IDRCB)

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. .

Suscribir