From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis

NCT04873492 | Recruiting

• 1 other identifier: RC20_0404
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

MS is a heterogeneous disease either in its response to treatment or clinical manifestation. Indeed, the natural history of MS is varying from a benign condition to a devastating and rapidly incapacitating disease. Clinical heterogeneity could also be cellular and / or molecular. The aim is to identify from OMIC analyses, at the early stage of the disease, differentially expressed molecules and / or cell subpopulations derived from CD8 + T lymphocytes and / or CD4 + T lymphocytes and / or B lymphocytes and monocytes from patients with aggressive versus non-aggressive, compared to a cohort of healthy controls

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Bulk RNA-sequencing

  Transcriptional profile of T and B cells in aggressive and non-aggressive MS and healthy volunteers. Measurement of gene expression of naïve and memory CD4+ and CD8+ T and B cell. Comparison of these expression level between MS patients with aggressive and non-aggressive form and healthy volunteers.

  Blood sample collection within 6 months after first inflammatory event for MS patients and at inclusion for healthy volunteers.

Secondary Outcomes (4)

• Single RNA sequencing

  Blood sample collection within 6 months after first inflammatory event.

• Association of genetic sequence variation from whole genome sequencing with gene expression profile via Bulk RNA-seq

  Blood sample collection within 6 months after first inflammatory event.

• Association of transcriptomic variation with DNA methylation

  Blood sample collection within 6 months after first inflammatory event.

• OMIC integration

  Blood sample collection within 6 months after first inflammatory event.

Study Arms (4)

Retrospective Aggressive MS patients

OTHER

Patients from who the clinical outcome is already known and classified as poor based on study definition detailed in inclusion criteria (retrospective arm). Blood sample collected after first event is available and used to characterize OMIC profile of T and B cells involve in MS.

Other: Biological sample collection

Retrospective Non Aggressive MS patient

OTHER

Patient from who the clinical outcome is already known and classified as non-aggressive based on study definition detailed in inclusion criteria (retrospective arm). Blood sample collected after first event is available and used to characterize OMIC profile of T and B cells involve in MS.

Other: Biological sample collection

Healthy volunteers

OTHER

Prospective arm use as comparator.

Other: Biological sample collection

Prospective MS patients

OTHER

MS patients from who the clinical outcome will be established at the end of the follow up. Blood sample will be collected after the first event to validate molecules of interest from OMIC results by using FACS a different technology and classify MS patient.

Other: Biological sample collection

Interventions

Biological sample collection OTHER

Venous blood sample will be collected from patients belonging to validation cohort and healthy volunteers at baseline resulting in 90 Ml EDTA tube and 10 ml serum tube. Approximately 100 ml will be collected. optional saliva and stool collection will be performed.

Healthy volunteers; Prospective MS patients; Retrospective Aggressive MS patients; Retrospective Non Aggressive MS patient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Common criteria for retrospective MS patients:
• Patients aged 18 years or older
• Clinical isolated syndrome (CIS) with or without dissemination in space
• Patients affiliated to an appropriate health insurance
• Criteria for Aggressive MS group
• Start of a 2nd line therapy within the two years following the CIS
• Criteria for Non aggressive MS group
• No conversion according to McDonald criteria from clinical isolated syndrome to multiple sclerosis within 2 years or
• Conversion based to McDonald criteria treated or not with first line disease modifying therapy within 2 years.
• Have a minimum of least 2 years of follow-up.
• Healthy volunteers
• Aged 18 years or older
• No history of clinically isolated syndrome or MS
• Pairing criteria :
• Age +/- 5 years

You may not qualify if:

• Ongoing participation to a another study
• Refusal to genetic analyses
• Immunosuppressive drug at the time of blood collection
• Plasma exchange or corticosteroid treatment within the four weeks prior to blood sample
• Adults under a legal protection regime (guardianship, trusteeship, judicial safeguard)
• Pregnancy

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes University Hospital

Nantes, Loire-Atlantique, 44093, France

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

David LAPLAUD, PhD

CONTACT

33 2 40 16 52 00; david.laplaud@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: NA/NO
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study model consists of two cohorts, the first one or "learning cohort" includes a group of health volunteers and 2 groups of MS patients from who clinical outcome (aggressive vs non-aggressive) is already known based on clinical follow up since first event. Clinical data and blood sample have been already collected and are available from OFSEP (Observatoire français de la Sclérose en plaques). Blood will be analyzed to characterize transcriptomic, epigenomic, genomic immune cells features to discover predictive markers of clinical outcome. The second cohort or "validation cohort" consists of MS patients enrolled after their first event and followed for maximum 2-years until the determination of their clinical outcome. Blood will be collected after their first event and used in FACS to classified the patients based on molecule of interest discover thanks to learning cohort and predict clinical outcome.

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 5, 2021
• Study Start: January 24, 2022
• Primary Completion (Estimated): July 24, 2029
• Study Completion (Estimated): July 24, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)