Stratification of Risks of Conversion of Radiologically Isolated Syndromes (RIS) by Identifying Biomarkers in Serum and Cerebrospinal Fluid.

NCT06395662 | Active Not Recruiting

• 1 other identifier: ProBioRIS
• Study Type: observational
• Target: 320
• Locations: 2 countries
• Sites: 3

Brief Summary

Radiologically isolated syndrome (RIS) often precedes Multiple Sclerosis (MS) but some patients have no symptoms. This study aims to use biological samples and magnetic resonance imaging (MRI) data from four large cohorts of patients with MS in the United States, Europe and France, to stratify the chances of RIS developing into MS. Identifying early biomarkers to predict greater disease severity would have a significant impact, not only on RIS but also on the entire clinical spectrum of multiple sclerosis.

Conditions

Radiologically Isolated Syndrome; Multiple Sclerosis

Keywords

Radiologically Isolated Syndrome; Multiple Sclerosis; Biomarkers

Outcome Measures

Primary Outcomes (8)

• Aim 1a : Association between Serum Neurofilament Light chain (sNfL) and RIS in all groups of patients

  Quantitative in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327

  Week 0

• Aim 1a : Association between Serum Neurofilament Light chain (sNfL) and RIS in all groups of patients

  Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327

  Week 96

• Aim 1a : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP) and RIS in all groups of patients

  Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327

  Week 0

• Aim 1a : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP) and RIS in all groups of patients

  Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327

  Week 96

• Aim 1b: Association between Serum Neurofilament Light chain (sNfL) and RIS in placebo-treated patients

  Serum Neurofilament Light chain (sNfL) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)

  Week 0

• Aim 1b: Association between Serum Neurofilament Light chain (sNfL) and RIS in placebo-treated patients

  Serum Neurofilament Light chain (sNfL) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)

  Week 96

• Aim 1b : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP)and RIS in placebo-treated patients

  Serum Glial Fibrillary Astrocytic Protein (sGFAP) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)

  Week 0

• Aim 1b: Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP)and RIS in placebo-treated patients

  Serum Glial Fibrillary Astrocytic Protein (sGFAP)will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)

  Week 96

Secondary Outcomes (16)

• Aim 2a: Kappa free light chain (KFLC) index in RIS patients in the SFSEP, OFSEP and ARISE cohorts, n=121

  Week 0

• Aim 2a: Kappa free light chain (KFLC) index in RIS patients in the SFSEP, OFSEP and ARISE cohorts, n=121

  Week 96

• Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.

  Week 0

• Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.

  Week 96

• Aim 2a: Chitinase-3-like protein 1 as a potential biomarker of RIS.

  Week 0

Other Outcomes (3)

• Age of patients who provided serum and cerebrospinal fluid samples

  Week 0

• Sex of patients who provided serum and cerebrospinal fluid samples

  Week 0

• Disease-Modifying Therapy exposure in patients who provided serum and cerebrospinal fluid samples

  Week 0

Study Arms (5)

ARISE cohort

n=87, clinicaltrials.gov NCT02739542

Other: Observational

TERIS cohort

n=90, clinicaltrials.gov NCT03122652

Other: Observational

OFSEP cohort

OFSEP, n=75

Other: Observational

SFSEP cohort

SFSEP, n=75

Other: Observational

Subset of serum and cerebrospinal biomarkers

As a validation group, the best subset of serum and cerebrospinal biomarkers from Objective 2a will be tested in a separate group of RIS patients. Their association with the same outcomes (clinical relapse and magnetic resonance imaging measurements of disease severity/activity) will be measured using the same regression techniques as in Objective 2a. This subset will consist of the remaining third of RIS patients from the SFSEP, OFSEP, and ARISE cohorts with serum and cerebrospinal fluid available (n=60)

Other: Observational

Interventions

Observational OTHER

Search for biomarkers

ARISE cohort; OFSEP cohort; SFSEP cohort; Subset of serum and cerebrospinal biomarkers; TERIS cohort

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients registered in the ARISE, TERIS, OFSEP and SFSEP cohorts.

You may qualify if:

• Patients from the OFSEP, SFSEP, RISE and TERIS cohorts with centralized validated radiologoically isolated syndrome and a standardized magnetic resonance imaging from the OFSEP or Randomized Clinical Trials database.
• at least one cerebro-spinal fluid and/or serum sample at baseline available at a local or centralized biological resource center.
• if present, serum sample collected at the time of clinical conversion.

You may not qualify if:

• patients with no biocollection, or with non-standardized magnetic resonance imaging acquisitions

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead
• International Center of Research in Infectiology, Lyon University: collaborator
• Universite Cote d'Azur: collaborator
• The University of Texas at Dallas: collaborator

Study Sites (3)

University of Texas, Southwestern

Dallas, Texas, 75390, United States

Location

COTE D'AZUR UNIVERSITY, URRIS-UR2CA. Hôpital Pasteur 2, 30, Voie Romaine

Nice, Alpes-Maritimes, 06001, France

Location

INTERNATIONAL CENTER OF RESEARCH IN INFECTIOLOGY, LYON UNIVERSITY, INSERM U1111, CNRS UMR 5308, ENS, UCBL 46 Allée d'Italie

Lyon, Rhône, 69364, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biological samples and magnetic resonance imaging data from four large cohorts of patients with multiple sclerosis in the United States, Europe and France will be used for this study. Indeed, this proposal is based on existing clinical and magnetic resonance imaging data and stored serum and cerebrospinal fluid samples from ARISE (clinicaltrials. gov NCT02739542) and TERIS (NCT03122652), which are randomized, double-blind, placebo-controlled trials in multiple sclerosis, as well as two prospective, real-world cohorts of multiple sclerosis patients from the French multiple sclerosis registry (OFSEP) and the French multiple sclerosis society (SFSEP).

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 2, 2024
• Study Start: April 15, 2024
• Primary Completion: December 1, 2024
• Study Completion: July 1, 2025
• Last Updated: November 1, 2024

Record last verified: 2024-10

Locations

FR (2); US (1)