Clinical trial NCT04873492: From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis
Official title: From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2021-05-05
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Bulk RNA-sequencing
timeFrame: Blood sample collection within 6 months after first inflammatory event for MS patients and at inclusion for healthy volunteers.
Secondary outcomes:
measure: Single RNA sequencing
timeFrame: Blood sample collection within 6 months after first inflammatory event.
measure: Association of genetic sequence variation from whole genome sequencing with gene expression profile via Bulk RNA-seq
timeFrame: Blood sample collection within 6 months after first inflammatory event.
measure: Association of transcriptomic variation with DNA methylation
timeFrame: Blood sample collection within 6 months after first inflammatory event.
measure: OMIC integration
timeFrame: Blood sample collection within 6 months after first inflammatory event.
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes University Hospital
state: Loire-Atlantique
Study officials:
References: