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

Multiple Sclerosis Clinical Trial

— OUTCOMS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04873492
• Other study ID #: RC20_0404
• Status: Recruiting
• Phase: N/A
• Start date: January 24, 2022
• Est. completion date: July 24, 2025

Study information

• Verified date: January 2023
• Source: Nantes University Hospital
• Contact: David LAPLAUD, PhD
• Phone: 33 2 40 16 52 00
• Email: david.laplaud[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: July 24, 2025
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• Adults under a legal protection regime (guardianship, trusteeship, judicial safeguard)
• Pregnancy

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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.

Locations

Country	Name	City	State
France	Nantes University Hospital	Nantes	Loire-Atlantique

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.