RIS International Cohort

The Radiologically Isolated Syndrome International Cohort

The Radiologically Isolated Syndrome (RIS) corresponds to the discovery of white matter (WM) abnormalities suggestive of multiple sclerosis (MS) by their location, size, and appearance, on the brain or spinal cord Magnetic Resonance Imaging (MRI). This imaging is performed for a reason other than for suspicion of demyelinating disease in subjects without a history of neurological symptoms and a strict routine clinical neurological examination. It was defined and named in 2009 (Okuda et al.) after publishing 3 case series (French, USA, Turkey). The Radiologically Isolated Syndrome Consortium (RISC) published a cohort of subjects with an extended follow-up after the first brain MRI of MS, with 34% presenting an event (clinical conversion) at five years, 51.2 % of these subjects showed an event at ten years. The patients who offer a higher risk of developing a first clinical demyelinating event were identified such as male sex, young age, the presence of oligoclonal bands (BOCs) in the Cerebrospinal Fluid (CSF), the presence of infratentorial lesions and spinal cord lesions on the first MRI suggestive of RIS. The location and morphology of the lesions appear to be decisive for studying the risk of conversion. Our first objective is to prospectively collect data to identify the subjects who present a higher risk of developing a first clinical demyelinating event and the progression of the disease in these subjects.

Among the objectives of this worldwide cohort is the analysis of (1) environmental factors (Vit D, EBV, tobacco…), (2) MRI biomarkers, including atrophy, central veins signs, paramagnetic rings, and DTI.

(3) digital biomarkers (4) oculography (5) biological markers To summarize, this cohort will allow for analyzing features in imaging, biology and the exploration of digital and oculographic characteristics to identify predictive factors of clinical evolution of a large cohort of subjects presenting WM abnormalities suggestive of multiple sclerosis.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Radiologically Isolated Syndrome
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Christine LEBNRUN-FRENAY; Phone Number: 33 4 92 03 41 26; Email: lebrun-frenay.c@chu-nice.fr
• Study Contact Backup: Name: Cassandre LANDES; Phone Number: 33 4 92 03 41 26; Email: landes.c@chu-nice.fr

Study Locations

• France
  • Nice, France, 06000
    • Recruiting
    • Nice University Hospital
    • Contact: Christine Lebrun-Frenay; Email: lebrun-frenay.c@chu-nice.fr
    • Contact: Cassandre Landes; Email: landes.c@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects demonstrating white matter T2 lesion suggestive of demyelination, asymptomatic with a normal neurological exam, corresponding to RIS diagnostic criteria.

Description

Inclusion Criteria:

• white matter T2 lesions suggestive of demyelination
• asymptomatic
• normal neurological exam

Exclusion Criteria:

• abnormal neurological exam,
• suspicion of another disease explaining MRI lesions.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RIS/1-2 criteria	Other: No intervention; No intervention
RIS/3-4 criteria	Other: No intervention; No intervention
NON RIS/0 criteria	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of lesions T2-weighted sequence at the index scan	number of T2-weighted sequence	at inclusion
Identification of lesions T2-weighted sequence at the index scan	localisation of interest of T2 lesion (juxtacortical, periventricular, infratentorial, spinal cord)	at inclusion
Identification of lesions T1 sequence with and without Gd at the index scan.	Lesions number	at inclusion
Identification of lesions T1 sequence with and without Gd at the index scan.	localisation of interest	at inclusion
Radiological progression : new T2 lesions	localisation of interest	year 1
Radiological progression : new contrast enhancing lesions	Lesions number	year 1
Radiological progression : new contrast enhancing lesions	localisation of interest	year 1
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	year 1
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	year 2
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	year 3
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	year 4
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	year 5
Brain atrophy	measurement of global and regional grey matter volume measurement of global and regional white matter volume	MS onset assessed up to 2 years
Radiological progression : new T2 lesions	number of T2-weighted sequence	year 2
Radiological progression : new T2 lesions	localisation of interest of T2 lesion	year 2
Radiological progression : new T2 lesions	number of T2-weighted sequence	year 3
Radiological progression : new T2 lesions	localisation of interest of T2 lesion	year 4
Radiological progression : new T2 lesions	number of T2-weighted sequence	year 5
Radiological progression : new T2 lesions	localisation of interest of T2 lesion	MS onset assessed up to 2 years
Radiological progression : new contrast enhancing lesions	localisation of interest	year 2
Radiological progression : new contrast enhancing lesions	Lesions number	year 2
Radiological progression : new contrast enhancing lesions	Lesions number	year 3
Radiological progression : new contrast enhancing lesions	localisation of interest	year 3
Radiological progression : new contrast enhancing lesions	Lesions number	year 4
Radiological progression : new contrast enhancing lesions	localisation of interest	year 4
Radiological progression : new contrast enhancing lesions	Lesions number	year 5
Radiological progression : new contrast enhancing lesions	localisation of interest	year 5
Radiological progression : new contrast enhancing lesions	Lesions number	MS onset assessed up to 2 years
Radiological progression : new contrast enhancing lesions	localisation of interest	MS onset assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collect biological data	number of plasma samples	At inclusion
Collect biological data	number of plasma samples	MS onset assessed up to 2 years
Collect digital markers	The number of abnormalities identified by the eVOG application correlated with cerebral atrophy	at inclusion
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	year 1
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	year 2
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	year 3
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	year 4
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	year 5
Collect digital markers	Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy	MS onset assessed up to 2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2022
• Primary Completion (ANTICIPATED): April 15, 2023
• Study Completion (ANTICIPATED): April 15, 2029

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (ACTUAL): May 24, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Multiple Sclerosis; Syndrome
• Other Study ID Numbers: 22Neuro01

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