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

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Biological sample collection
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Multiple Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Nantes University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Retrospective Aggressive MS patients

Retrospective Non Aggressive MS patient

Healthy volunteers

Prospective MS patients

Arm Description

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.

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.

Prospective arm use as comparator.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
April 30, 2021
Last Updated
January 27, 2023
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04873492
Brief Title
From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis
Acronym
OUTCOMS
Official Title
From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
July 24, 2023 (Anticipated)
Study Completion Date
July 24, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Masking Description
NA/NO
Allocation
Non-Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Retrospective Aggressive MS patients
Arm Type
Other
Arm Description
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.
Arm Title
Retrospective Non Aggressive MS patient
Arm Type
Other
Arm Description
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.
Arm Title
Healthy volunteers
Arm Type
Other
Arm Description
Prospective arm use as comparator.
Arm Title
Prospective MS patients
Arm Type
Other
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Biological sample collection
Intervention Description
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.
Primary Outcome Measure Information:
Title
Bulk RNA-sequencing
Description
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.
Time Frame
Blood sample collection within 6 months after first inflammatory event for MS patients and at inclusion for healthy volunteers.
Secondary Outcome Measure Information:
Title
Single RNA sequencing
Description
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.
Time Frame
Blood sample collection within 6 months after first inflammatory event.
Title
Association of genetic sequence variation from whole genome sequencing with gene expression profile via Bulk RNA-seq
Description
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.
Time Frame
Blood sample collection within 6 months after first inflammatory event.
Title
Association of transcriptomic variation with DNA methylation
Description
Add Analyzes of gene expression regulation throughout DNA methylation of CpG sites to RNA seq analyses related to MS.
Time Frame
Blood sample collection within 6 months after first inflammatory event.
Title
OMIC integration
Description
Developing machine learning method to combine genomic, epigenomic transcriptomic and clinical data to pinpoint genes of interest particularly involved in aggressive MS outcomes.
Time Frame
Blood sample collection within 6 months after first inflammatory event.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David LAPLAUD, PhD
Phone
33 2 40 16 52 00
Email
david.laplaud@chu-nantes.fr
Facility Information:
Facility Name
Nantes University Hospital
City
Nantes
State/Province
Loire-Atlantique
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David LAPLAUD, Phd
Phone
33240165200
Email
david.laplaud@chu-nantes.fr

12. IPD Sharing Statement

Plan to Share IPD
No

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

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