Multiple SclerosisNeuroDIPNCT07902479
Neurogenetics and Multi-omics of Neuroinflammatory Diseases in Multiplex Families to Improve Patients Health
A study testing Blood sampling and multi-omic profiling in people with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 15 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, MOG Antibody-Associated Disease
- What is being tested?
- Blood sampling and multi-omic profiling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 5 sitesFrance
- Study dates
- Nov 2026to Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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)
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites
Hospice Civil de Lyon - Hospital Pierre Wertheimer
Bron, 69500
Sandra VUKUSIC, +33 04 72 68 13 13, sandra.vukusic@chu-lyon.fr
Sandra Vukusic
University Hospital Laennec
Nantes, 44000
David-Axel LAPLAUD, +33 02 40 16 52 00, david.laplaud@chu-nantes.fr
David-Axel LAPLAUD
University Hospital Pasteur 2
Nice, 06002
Christine LEBRUN-FRENAY, +33 04 92 03 71 00, lebrun-frenay.c@chu-nice.fr
Christine LEBRUN-FRENAY
Assistance Publique Hôpitaux de Paris- La Pitié Salpêtrière Hospital
Paris, 75013
Céline a LOUAPRE, +33 01 42 16 57 66, celine.louapre@aphp.fr
Céline LOUAPRE
University Hospital Pontchaillou
Rennes, 35000
Laure MICHEL, +33 02 99 28 42 66, laure.michel@chu-rennes.fr
Laure MICHEL
About this study
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
Read the detailed description
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.
- Conditions
- Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, MOG Antibody-Associated Disease, Demyelinating Autoimmune Diseases, CNS
- Being tested
- Blood sampling and multi-omic profiling
- Keywords
- multiplex families, whole genome sequencing, rare variants, co-segregation, DNA methylation, RNA sequencing, eQTL, HLA, multi-omics, neuroinflammation
- Medical subject headings
- Multiple Sclerosis, Neuromyelitis Optica, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, Demyelinating Autoimmune Diseases, CNS, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampling and multi-omic profilingDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Multiplex family members (patients and relatives) | Other | Four participant categories (people with MS, NMOSD, MOGAD, and healthy) with their approximate numbers. Receives: Diagnostic Test: Blood sampling and multi-omic profiling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rare high-penetrance variants co-segregating with disease within multiplex families.
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.
Measured: 36 months from the first inclusion.
Secondary outcomes (5)
eQTL: genetic loci associated with gene expression in PBMC
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.
Measured: 36 months from the first inclusion.
Disease-associated DNA methylation (CpG sites)
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.
Measured: 36 months from the first inclusion.
Transcriptomic signatures of PBMC subpopulations
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.
Measured: 36 months from the first inclusion.
Multi-omic molecular signatures
Molecular signatures obtained by integrating genomic, DNA methylation and transcriptomic data (omicsNPC framework, multilevel modelling), used to model familial risk.
Measured: 36 months from the first inclusion.
Evaluation of the correlation with the disease phenotype
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.
Measured: 36 months from the first inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants follow the same single-visit procedures (clinical data collection and one blood sample). No intervention is assigned. Affected members and unaffected relatives of the same family are compared at the analysis stage.
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- Université de Nantes, Nantes University Hospital, Fondation ARSEP
- Responsible party
- Sponsor
- Investigators
- Nicolas VINCE, PhD, Principal investigator, Nantes Université
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07902479
- Sponsor's protocol ID
- C25-79
- Other IDs
- 2026-A01125-46
- Acronym
- NeuroDIP
- Status last verified
- Nov 2026
- First submitted
- 13 Oct 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460):eaav7188. doi: 10.1126/science.aav7188.
PubMed 31604244Horjus J, van Mourik-Banda T, Heerings MAP, Hakobjan M, De Witte W, Heersema DJ, Jansen AJ, Strijbis EMM, de Jong BA, Slettenaar AEJ, Zeinstra EMPE, Hoogervorst ELJ, Franke B, Kruijer W, Jongen PJ, Visser LJ, Poelmans G. Whole Exome Sequencing in Multi-Incident Families Identifies Novel Candidate Genes for Multiple Sclerosis. Int J Mol Sci. 2022 Sep 28;23(19):11461. doi: 10.3390/ijms231911461.
PubMed 36232761Wannaphut C, Ongphichetmetha T, Satiraphan P, Jitprapaikulsan J, Apiwattanakul M, Siritho S, Prayoonwiwat N, Savangned P, Rattanathamsakul N. Familial neuromyelitis optica spectrum disorders: Case series and systematic review. Mult Scler Relat Disord. 2023 May;73:104627. doi: 10.1016/j.msard.2023.104627. Epub 2023 Mar 21.
PubMed 37015139
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurogenetics and Multi-omics of Neuroinflammatory Diseases in Multiplex Families to Improve Patients Health
- ClinicalTrials.gov ID
- NCT07902479
- Acronym / sponsor ID
- NeuroDIP / C25-79
- Conditions
- Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, MOG Antibody-Associated Disease, Demyelinating Autoimmune Diseases, CNS
- Keywords
- multiplex families, whole genome sequencing, rare variants, co-segregation, DNA methylation, RNA sequencing, eQTL, HLA
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- Université de Nantes, Nantes University Hospital, Fondation ARSEP
- Study start
- Nov 2026 (estimated)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 28 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants follow the same single-visit procedures (clinical data collection and one blood sample). No intervention is assigned. Affected members and unaffected relatives of the same family are compared at the analysis stage.
| Arm | Type | Receives |
|---|---|---|
| Multiplex family members (patients and relatives) | Other | Diagnostic Test: Blood sampling and multi-omic profilingFour participant categories (people with MS, NMOSD, MOGAD, and healthy) with their approximate numbers. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Affected participants:
- Unaffected relatives:
- Transcriptomic sub-cohort (30 to 60 participants, about 10 families):
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sampling and multi-omic profilingOne 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. | Diagnostic test | Multiplex family members (patients and relatives) |
Primary outcome
Rare high-penetrance variants co-segregating with disease within multiplex families.
Time frame: 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.
5 secondary outcomes
eQTL: genetic loci associated with gene expression in PBMC
Time frame: 36 months from the first inclusion.
Disease-associated DNA methylation (CpG sites)
Time frame: 36 months from the first inclusion.
Transcriptomic signatures of PBMC subpopulations
Time frame: 36 months from the first inclusion.
Multi-omic molecular signatures
Time frame: 36 months from the first inclusion.
Evaluation of the correlation with the disease phenotype
Time frame: 36 months from the first inclusion.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Background: PubMed 31604244International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460):eaav7188. doi: 10.1126/science.aav7188.
- Background: PubMed 36232761Horjus J, van Mourik-Banda T, Heerings MAP, Hakobjan M, De Witte W, Heersema DJ, Jansen AJ, Strijbis EMM, de Jong BA, Slettenaar AEJ, Zeinstra EMPE, Hoogervorst ELJ, Franke B, Kruijer W, Jongen PJ, Visser LJ, Poelmans G. Whole Exome Sequencing in Multi-Incident Families Identifies Novel Candidate Genes for Multiple Sclerosis. Int J Mol Sci. 2022 Sep 28;23(19):11461. doi: 10.3390/ijms231911461.
- Background: PubMed 37015139Wannaphut C, Ongphichetmetha T, Satiraphan P, Jitprapaikulsan J, Apiwattanakul M, Siritho S, Prayoonwiwat N, Savangned P, Rattanathamsakul N. Familial neuromyelitis optica spectrum disorders: Case series and systematic review. Mult Scler Relat Disord. 2023 May;73:104627. doi: 10.1016/j.msard.2023.104627. Epub 2023 Mar 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicolas VINCE, PhD principal investigator
Nantes Université
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling and multi-omic profiling in people with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Axel LAPLAUD, MD PhD (+33 240165176, david.laplaud@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rare high-penetrance variants co-segregating with disease within multiplex families. (time frame: 36 months from the first inclusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07902479, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.