Radiologically Isolated SyndromeProBioRISNCT06395662
Stratification of Risks of Conversion of Radiologically Isolated Syndromes (RIS) by Identifying Biomarkers in Serum and Cerebrospinal Fluid.
An observational study of Radiologically Isolated Syndrome and Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nīmes at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Radiologically Isolated Syndrome, Multiple Sclerosis
- What is being tested?
- Observational
- How many people
- 320 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 15 Apr 2024to 25 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Child, Adult, Older adult
Study population: All patients registered in the ARISE, TERIS, OFSEP and SFSEP cohorts.
Who may be able to join
- 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.
Who cannot join
- patients with no biocollection, or with non-standardized magnetic resonance imaging acquisitions
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
France2 sites
INTERNATIONAL CENTER OF RESEARCH IN INFECTIOLOGY, LYON UNIVERSITY, INSERM U1111, CNRS UMR 5308, ENS, UCBL 46 Allée d'Italie
Lyon, Rhône, 69364
COTE D'AZUR UNIVERSITY, URRIS-UR2CA. Hôpital Pasteur 2, 30, Voie Romaine
Nice, Alpes-Maritimes, 06001
United States1 site
University of Texas, Southwestern
Dallas, Texas, 75390
About this study
Official title: Improving the Stratification of Risks of Conversion of Radiologically Isolated Syndromes (RIS) by Identifying Biomarkers in Serum and Cerebrospinal Fluid. The ProBioRIS Study
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.
Read the detailed description
Radiologically Isolated Syndrome (RIS) is defined as the presence of asymptomatic, idiopathic demyelinating-appearing white matter lesions in the central nervous system. RIS often precedes clinical multiple sclerosis. Data from the international RIS Consortium indicate that 34% of RIS patients will have their first multiple sclerosis symptom within 5 years, and 51% within 10 years, making RIS the earliest identifiable phase of MS. While most RIS patients will evolve to relapsing MS, ~10% directly evolve towards progressive multiple sclerosis. RIS is an informative cohort for studying the earliest pathophysiologic changes, but remains a significant challenge for MS clinicians, as not all RIS patients will develop clinical symptoms. There is a need to distinguish RIS patients at high risk of clinical MS from those who will remain asymptomatic. Stratification would be invaluable to inform treatment/monitoring recommendations and counsel patients.
In the RIS Consortium cohort, age at diagnosis, positive CSF oligoclonal bands (OCBs) or elevated IgG index, infratentorial or spinal cord lesions, and gadolinium-enhancing (Gd+) lesions during follow-up independently predicted a first clinical event at 10 years. Additional serum and CSF biomarkers may further refine the risk stratification for clinical MS and may predict more severe tissue injury measured by MRI.
Serum and cerebrospinal fluid biomarkers can refine risk stratification of the progression from risk to clinical multiple sclerosis and predict more severe tissue damage as measured by magnetic resonance imaging. 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. However, RIS remains a rare disease and large cohorts are needed to validate potential prognostic biomarkers.
The international RIS Consortium has had a unique opportunity to apply for a research grant from the National Multiple Sclerosis Society to combine biomarker expertise, advanced magnetic resonance imaging analysis, and collaborative networks and cohorts to refine the prognosis of multiple sclerosis. Here, the proposal is to use biological samples and magnetic resonance imaging data from four large cohorts of patients with multiple sclerosis in the United States, Europe and France. In fact, this proposal is based on existing clinical and magnetic resonance imaging data and stored serum and cerebrospinal fluid samples from the ARISE (clinicaltrials. gov NCT02739542) and TERIS (NCT03122652) trials, which are randomized, double-blind, placebo-controlled trials on multiple sclerosis, as well as two prospective, real-world cohorts of multiple sclerosis patients from the French multiple sclerosis observatory (OFSEP = Observatoire Français de la Sclérose en Plaques) and the French multiple sclerosis society (SFSEP = Société Francophone de la Sclérose En Plaques).
The French observatory for multiple sclerosis, coordinated by Professor Sandra Vukusic in Lyon, brings together neurologists from all over France and 61 centers that use the European Database for Multiple Sclerosis, including 31 French hospitals and expert centers, and more than 45,000 people with multiple sclerosis or related diseases (half the population with multiple sclerosis in France). This includes a priority effort involving at least 85 RIS patients validated by the central supervision of the RIS consortium (Prof. Christine Lebrun-Frenay, Nice), with longitudinal follow-up and systematic association of clinical data with biological samples and neuro-imaging.
Standardized biological samples obtained from RIS patients and banked in certified biological resource centers guarantee the high quality of biological samples associated with clinical and medical imaging data collected prospectively in the EDMUS database. This biocollection offers a unique opportunity to identify and validate potential biomarkers of disease activity and clinical conversion in RIS patients, notably in association with those of randomized clinical trials and the SFSEP, which relies on the same French network of experts in multiple sclerosis (CRC-SEP = Centres de Ressources et de Compétences sur la Sclérose en Plaques) and biological research centers.
The hypothesis is that increases in the serum Neurofilament Light (sNfl) chain and serum Glial Fibrillary Astrocytic Protein (sGFAP) will be associated with higher numbers of new gadolinium-enhancing (Gd+) lesions, higher T2 lesion volume, higher rates of clinical relapse, and faster thalamic volume decline over 96 weeks.
- Being tested
- Observational
- Keywords
- Radiologically Isolated Syndrome, Multiple Sclerosis, Biomarkers
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
Search for biomarkers
| Study group | Role | What they receive |
|---|---|---|
| ARISE cohort | n=87, clinicaltrials.gov NCT02739542 Receives: Other: Observational | |
| TERIS cohort | n=90, clinicaltrials.gov NCT03122652 Receives: Other: Observational | |
| OFSEP cohort | OFSEP, n=75 Receives: Other: Observational | |
| SFSEP cohort | SFSEP, n=75 Receives: 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) Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
CSF NfL, CHI3L1, and OCBs have been tested as predictors of clinical evolution in RIS, but a comprehensive examination of a large number of candidate serum and CSF biomarkers has not been undertaken. The kappa free light chain (KFLC) index will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) by cytokine multiplex assay (ProcartaPlexTM and Simoa TM). Regression techniques (chosen according to the outcome variable) will measure the univariate association between each CSF and serum biomarker and the number of Gd+ lesions, T2LV, and thalamic volume at study entry and new T2/Gd+ lesions, clinical relapse, and thalamic volume decline over time. Machine learning (LASSO; SAS HPGENSELECT) will select the final set of biomarkers most strongly associated with clinical and MRI measures.
Measured: Week 0
Aim 2a: Kappa free light chain (KFLC) index in RIS patients in the SFSEP, OFSEP and ARISE cohorts, n=121
CSF NfL, CHI3L1, and OCBs have been tested as predictors of clinical evolution in RIS, but a comprehensive examination of a large number of candidate serum and CSF biomarkers has not been undertaken. The kappa free light chain (KFLC) index will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) by Binding Site Optilite analyzer. Regression techniques (chosen according to the outcome variable) will measure the univariate association between each CSF and serum biomarker and the number of Gd+ lesions, T2LV, and thalamic volume at study entry and new T2/Gd+ lesions, clinical relapse, and thalamic volume decline over time. Machine learning (LASSO; SAS HPGENSELECT) will select the final set of biomarkers most strongly associated with clinical and MRI measures.
Measured: Week 96
Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
The neurofilament light chain will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (Simoa TM).
Measured: Week 0
Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
The neurofilament light chain will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (Simoa TM).
Measured: Week 96
Aim 2a: Chitinase-3-like protein 1 as a potential biomarker of RIS.
Chitinase-3-like protein 1will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (ProcartaPlexTM).
Measured: Week 0
Aim 2a: Chitinase-3-like protein 1 as a potential biomarker of RIS.
Chitinase-3-like protein 1will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (ProcartaPlexTM).
Measured: Week 96
Aim 2a: Oligoclonal bands as a potential biomarker of RIS.
Oligoclonal bands will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 0
Aim 2a: Oligoclonal bands as a potential biomarker of RIS.
Oligoclonal bands will be measured in two-thirds of the total cerebral spinal fluid samples available (n= 121) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 96
Aim 2b: Validation of cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
The neurofilament light chain will be measured in the remaining third of the total cerebral spinal fluid samples available (n= 60) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 0
Aim 2b: Validation of cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
The neurofilament light chain will be measured in the remaining third of the total cerebral spinal fluid samples available (n= 60) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 96
Aim 2b: Validation of chitinase-3-like protein 1 as a potential biomarker of RIS.
Chitinase-3-like protein 1 will be measured in the remaining third of the total cerebral spinal fluid samples available (n=60) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (ProcartaPlexTM).
Measured: Week 0
Aim 2b: Validation of chitinase-3-like protein 1 as a potential biomarker of RIS.
Chitinase-3-like protein 1 will be measured in the remaining third of the total cerebral spinal fluid samples available (n=60) from patients in the SFSEP, OFSEP and ARISE cohorts by cytokine multiplex assay (ProcartaPlexTM).
Measured: Week 96
Aim 2b: Validation of oligoclonal bands as a potential biomarker of RIS.
Oligoclonal bands will be measured in the remaining third of the total cerebral spinal fluid samples available (n=60) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 0
Aim 2b: Validation of oligoclonal bands as a potential biomarker of RIS.
Oligoclonal bands will be measured in the remaining third of the total cerebral spinal fluid samples available (n=60) from patients in the SFSEP, OFSEP and ARISE cohorts by isoelectric focusing.
Measured: Week 96
Aim 3: Improving prediction of clinical disease activity of RIS
Using patients from Aim 2 (n=181), a multivariate Cox regression model including known predictors of clinical disease activity (sex, age, OCBs, infratentorial and spinal cord lesions, Gd+ lesions, and DMT exposure) will be built to discern the added value of sNfL, sGFAP, and our final set of biomarkers from Aim 2 to predict clinical disease. Biomarker thresholds will be defined based on the distribution of the data.
Measured: Week 0
Aim 3: Improving prediction of clinical disease activity of RIS
Using patients from Aim 2 (n=181), a multivariate Cox regression model including known predictors of clinical disease activity (sex, age, OCBs, infratentorial and spinal cord lesions, Gd+ lesions, and DMT exposure) will be built to discern the added value of sNfL, sGFAP, and our final set of biomarkers from Aim 2 to predict clinical disease. Biomarker thresholds will be defined based on the distribution of the data.
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2024
- Study start15 Apr 2024
- Primary completion25 Jul 2025
- Study completion25 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Radiologically Isolated SyndromeStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NīmesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Collaborators
- International Center of Research in Infectiology, Lyon University, Universite Cote d'Azur, The University of Texas at Dallas
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06395662
- Sponsor's protocol ID
- ProBioRIS
- Acronym
- ProBioRIS
- Status last verified
- May 2026
- First submitted
- 29 Apr 2024
- Last updated
- 1 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving the Stratification of Risks of Conversion of Radiologically Isolated Syndromes (RIS) by Identifying Biomarkers in Serum and Cerebrospinal Fluid. The ProBioRIS Study
- ClinicalTrials.gov ID
- NCT06395662
- Acronym / sponsor ID
- ProBioRIS / ProBioRIS
- Keywords
- Radiologically Isolated Syndrome, Multiple Sclerosis, Biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NīmesUniversity, hospital or other
- Collaborators
- International Center of Research in Infectiology, Lyon University, Universite Cote d'Azur, The University of Texas at Dallas
- Study start
- 15 Apr 2024 (actual)
- Primary completion
- 25 Jul 2025 (actual)
- Study completion
- 25 Jul 2025 (actual)
- First posted
- 2 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Radiologically Isolated Syndrome (RIS) is defined as the presence of asymptomatic, idiopathic demyelinating-appearing white matter lesions in the central nervous system. RIS often precedes clinical multiple sclerosis. Data from the international RIS Consortium indicate that 34% of RIS patients will have their first multiple sclerosis symptom within 5 years, and 51% within 10 years, making RIS the earliest identifiable phase of MS. While most RIS patients will evolve to relapsing MS, ~10% directly evolve towards progressive multiple sclerosis. RIS is an informative cohort for studying the earliest pathophysiologic changes, but remains a significant challenge for MS clinicians, as not all RIS patients will develop clinical symptoms. There is a need to distinguish RIS patients at high risk of clinical MS from those who will remain asymptomatic. Stratification would be invaluable to inform treatment/monitoring recommendations and counsel patients.
In the RIS Consortium cohort, age at diagnosis, positive CSF oligoclonal bands (OCBs) or elevated IgG index, infratentorial or spinal cord lesions, and gadolinium-enhancing (Gd+) lesions during follow-up independently predicted a first clinical event at 10 years. Additional serum and CSF biomarkers may further refine the risk stratification for clinical MS and may predict more severe tissue injury measured by MRI.
Serum and cerebrospinal fluid biomarkers can refine risk stratification of the progression from risk to clinical multiple sclerosis and predict more severe tissue damage as measured by magnetic resonance imaging. 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. However, RIS remains a rare disease and large cohorts are needed to validate potential prognostic biomarkers.
The international RIS Consortium has had a unique opportunity to apply for a research grant from the National Multiple Sclerosis Society to combine biomarker expertise, advanced magnetic resonance imaging analysis, and collaborative networks and cohorts to refine the prognosis of multiple sclerosis. Here, the proposal is to use biological samples and magnetic resonance imaging data from four large cohorts of patients with multiple sclerosis in the United States, Europe and France. In fact, this proposal is based on existing clinical and magnetic resonance imaging data and stored serum and cerebrospinal fluid samples from the ARISE (clinicaltrials. gov NCT02739542) and TERIS (NCT03122652) trials, which are randomized, double-blind, placebo-controlled trials on multiple sclerosis, as well as two prospective, real-world cohorts of multiple sclerosis patients from the French multiple sclerosis observatory (OFSEP = Observatoire Français de la Sclérose en Plaques) and the French multiple sclerosis society (SFSEP = Société Francophone de la Sclérose En Plaques).
The French observatory for multiple sclerosis, coordinated by Professor Sandra Vukusic in Lyon, brings together neurologists from all over France and 61 centers that use the European Database for Multiple Sclerosis, including 31 French hospitals and expert centers, and more than 45,000 people with multiple sclerosis or related diseases (half the population with multiple sclerosis in France). This includes a priority effort involving at least 85 RIS patients validated by the central supervision of the RIS consortium (Prof. Christine Lebrun-Frenay, Nice), with longitudinal follow-up and systematic association of clinical data with biological samples and neuro-imaging.
Standardized biological samples obtained from RIS patients and banked in certified biological resource centers guarantee the high quality of biological samples associated with clinical and medical imaging data collected prospectively in the EDMUS database. This biocollection offers a unique opportunity to identify and validate potential biomarkers of disease activity and clinical conversion in RIS patients, notably in association with those of randomized clinical trials and the SFSEP, which relies on the same French network of experts in multiple sclerosis (CRC-SEP = Centres de Ressources et de Compétences sur la Sclérose en Plaques) and biological research centers.
The hypothesis is that increases in the serum Neurofilament Light (sNfl) chain and serum Glial Fibrillary Astrocytic Protein (sGFAP) will be associated with higher numbers of new gadolinium-enhancing (Gd+) lesions, higher T2 lesion volume, higher rates of clinical relapse, and faster thalamic volume decline over 96 weeks.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| ARISE cohort | – | Other: Observationaln=87, clinicaltrials.gov NCT02739542 |
| TERIS cohort | – | Other: Observationaln=90, clinicaltrials.gov NCT03122652 |
| OFSEP cohort | – | Other: ObservationalOFSEP, n=75 |
| SFSEP cohort | – | Other: ObservationalSFSEP, n=75 |
| Subset of serum and cerebrospinal biomarkers | – | Other: ObservationalAs 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) |
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- All patients registered in the ARISE, TERIS, OFSEP and SFSEP cohorts.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (1 listed)
- patients with no biocollection, or with non-standardized magnetic resonance imaging acquisitions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObservationalSearch for biomarkers | Other | ARISE cohort, OFSEP cohort, SFSEP cohort, Subset of serum and cerebrospinal biomarkers, TERIS cohort |
Primary outcome
Aim 1a : Association between Serum Neurofilament Light chain (sNfL) and RIS in all groups of patients
Time frame: Week 0
Quantitative in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327
Aim 1a : Association between Serum Neurofilament Light chain (sNfL) and RIS in all groups of patients
Time frame: Week 96
Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327
Aim 1a : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP) and RIS in all groups of patients
Time frame: Week 0
Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327
Aim 1a : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP) and RIS in all groups of patients
Time frame: Week 96
Quantitative, in g/mL, SIMOA (TM) in all cohorts: ARISE, TERIS, OFSEP and SFSEP. n=327
Aim 1b: Association between Serum Neurofilament Light chain (sNfL) and RIS in placebo-treated patients
Time frame: Week 0
Serum Neurofilament Light chain (sNfL) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)
Aim 1b: Association between Serum Neurofilament Light chain (sNfL) and RIS in placebo-treated patients
Time frame: Week 96
Serum Neurofilament Light chain (sNfL) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)
Aim 1b : Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP)and RIS in placebo-treated patients
Time frame: Week 0
Serum Glial Fibrillary Astrocytic Protein (sGFAP) will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)
Aim 1b: Association between Serum Glial Fibrillary Astrocytic Protein (sGFAP)and RIS in placebo-treated patients
Time frame: Week 96
Serum Glial Fibrillary Astrocytic Protein (sGFAP)will be measured in placebo-treated patients from the ARISE and TERIS cohorts (n= 88)
16 secondary outcomes
Aim 2a: Kappa free light chain (KFLC) index in RIS patients in the SFSEP, OFSEP and ARISE cohorts, n=121
Time frame: Week 0
Aim 2a: Kappa free light chain (KFLC) index in RIS patients in the SFSEP, OFSEP and ARISE cohorts, n=121
Time frame: Week 96
Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
Time frame: Week 0
Aim 2a: Cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
Time frame: Week 96
Aim 2a: Chitinase-3-like protein 1 as a potential biomarker of RIS.
Time frame: Week 0
Aim 2a: Chitinase-3-like protein 1 as a potential biomarker of RIS.
Time frame: Week 96
Aim 2a: Oligoclonal bands as a potential biomarker of RIS.
Time frame: Week 0
Aim 2a: Oligoclonal bands as a potential biomarker of RIS.
Time frame: Week 96
Aim 2b: Validation of cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
Time frame: Week 0
Aim 2b: Validation of cerebrospinal fluid neurofilament light chain as a potential biomarker of RIS.
Time frame: Week 96
Aim 2b: Validation of chitinase-3-like protein 1 as a potential biomarker of RIS.
Time frame: Week 0
Aim 2b: Validation of chitinase-3-like protein 1 as a potential biomarker of RIS.
Time frame: Week 96
Aim 2b: Validation of oligoclonal bands as a potential biomarker of RIS.
Time frame: Week 0
Aim 2b: Validation of oligoclonal bands as a potential biomarker of RIS.
Time frame: Week 96
Aim 3: Improving prediction of clinical disease activity of RIS
Time frame: Week 0
Aim 3: Improving prediction of clinical disease activity of RIS
Time frame: Week 96
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
Related trials for Radiologically Isolated Syndrome
Recruiting
Diagnostic Value of eVOG
Multiple Sclerosis, Radiologically Isolated Syndrome
Enrolling by invitationObservational study
The Italian Multiple Sclerosis and Related Disorders Register
Multiple Sclerosis, Neuromyelitis Optica
Recruiting
Comparison of Digital Biomarkers in Subjects With Radiologically Isolated Syndrome (RIS) and Multiple Sclerosis (MS) Patients With Clinically Normal Neurological Examination
Radiologically Isolated Syndromes; Multiple Sclerosis
RecruitingObservational study
Clinical Impact Through AI-assisted MS Care - A Retrospective Multi-center Observational Study.
Multiple Sclerosis, NMO Spectrum Disorder
Enrolling by invitation
Clinical Impact Through AI-assisted MS Care - A Prospective Multi-center Study
Multiple Sclerosis, Radiologically Isolated Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Radiologically Isolated Syndrome and Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nīmes at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aim 1a : Association between Serum Neurofilament Light chain (sNfL) and RIS in all groups of patients (time frame: Week 0). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.