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

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Biological sample collection

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David LAPLAUD, PhD; Phone Number: 33 2 40 16 52 00; Email: david.laplaud@chu-nantes.fr

Study Locations

• France
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Recruiting
      • Nantes University Hospital
      • Contact: David LAPLAUD, Phd; Phone Number: 33240165200; Email: david.laplaud@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria :

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
• Sex

Prospective 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

Exclusion Criteria :

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Retrospective Aggressive MS patients; 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; 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.
Other: Retrospective Non Aggressive MS patient; 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; 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.
Other: Healthy volunteers; Prospective arm use as comparator.	Other: Biological sample collection; 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.
Other: Prospective MS patients; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single RNA sequencing	Single cell transcriptomics of T and B cells in order to identify by clustering, sub populations within these cells based on gene expression and associated to poor pronostic.	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	Add genetic variant analyzes to RNA seq analyses related to MS 1) Identify eQTL. 2 Impute SNPs result to calculate MS Genetic Burden (MSGB) a polygenic risk score of MS computed based on a weighted scoring algorithm using independent MS-SNPs.	Blood sample collection within 6 months after first inflammatory event.
Association of transcriptomic variation with DNA methylation	Add Analyzes of gene expression regulation throughout DNA methylation of CpG sites to RNA seq analyses related to MS.	Blood sample collection within 6 months after first inflammatory event.
OMIC integration	Developing machine learning method to combine genomic, epigenomic transcriptomic and clinical data to pinpoint genes of interest particularly involved in aggressive MS outcomes.	Blood sample collection within 6 months after first inflammatory event.

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Estimated): July 24, 2029
• Study Completion (Estimated): July 24, 2029

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: RC20_0404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No