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

2. november 2026 oppdatert av: 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

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

500

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

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

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

15 år og eldre (Barn, Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Annen: Multiplex family members (patients and relatives)

Four participant categories (people with MS, NMOSD, MOGAD, and healthy) with their approximate numbers.
Diagnostisk test: 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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Rare high-penetrance variants co-segregating with disease within multiplex families.
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
eQTL: genetic loci associated with gene expression in PBMC
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

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

Samarbeidspartnere

Nantes University Hospital
Université de Nantes
Fondation ARSEP

Etterforskere

  • Hovedetterforsker: Nicolas VINCE, PhD, Nantes Université

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

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 (Antatt)

1. november 2026

Primær fullføring (Antatt)

1. april 2029

Studiet fullført (Antatt)

1. oktober 2029

Datoer for studieregistrering

Først innsendt

13. oktober 2026

Først innsendt som oppfylte QC-kriteriene

22. oktober 2026

Først lagt ut (Faktiske)

28. oktober 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

4. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

2. november 2026

Sist bekreftet

1. november 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • C25-79
  • 2026-A01125-46 (Registeridentifikator: IDRCB)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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