Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity

NCT07292480 | Recruiting

• 1 other identifier: FINEX/2025/ET-01
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

Brief Summary

Reference MRI scan is recommended 6 months after treatment onset in patients with multiple sclerosis (MS), and follow-up scans at 12 months later to monitor subclinical activity. When monitoring treatment response in patients treated with disease modifying treatments (DMTs), the measurement of new or enlarging T2/FLAIR hyperintense lesions (NELs) is the preferred MRI method supplemented by contrast-enhancing lesions (CELs) for monitoring treatment response. However, some studies have suggested the deposition of gadolinium-based contrast agents in the basal ganglia and dentate nucleus of patients who underwent serial MRI acquisitions. Although significant clinical consequences of these deposits have not been demonstrated, further studies are required to better understand the potential long-term biological and clinical effects of gadolinium administration. To circumvent this potential risk, several recommendations suggested avoiding unnecessary use of gadolinium for follow-up scans. New sequences are also developed to replace gadolinium injection for the detection of active lesions. Moreover, MRI remains costly and time-consuming. In addition, systematic yearly MRI monitoring is not adapted to detect silent active lesions. This can delay identification of treatment failure and increase the risk of relapses and disability worsening, especially in the context of escalation therapy. Therefore, biological markers could allow more frequent analysis of disease activity and detect treatment failure earlier than classical clinical and MRI monitoring. Their use would greatly help clinicians to switch for high efficacy treatments (HET) and avoid potential relapses. Measurement of a structural axonal protein, neurofilament, in serum or plasma has shown promise as a marker of neuroaxonal injury and a measure of treatment response. In MS, cerebrospinal fluid (CSF) neurofilament-light chain (NfL) is also increased and is positively associated with MRI lesion load and disability scores and is a marker of treatment response. WThe study authors hypothesize that monthly plasma neurofilament-light chain (pNfL) monitoring can sensitively highlight subclinical (radiological disease activity) RDA by performing early MRI scans to confirm EDA and lead to timely treatment escalation. The main objective of this study is to compare the time to EDA in both arms (monthly pNfL monitoring vs. standard care with regular MRI scans), in patients with EDA.

Conditions

Multiple Sclerosis (MS) - Relapsing-remitting

Keywords

Biomarker

Outcome Measures

Primary Outcomes (2)

• Time to evidence of disease activity between groups

  As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan

  week 48

• Time to evidence of disease activity between groups

  As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan

  week 96

Secondary Outcomes (12)

• Proportion of CELs between groups

  week 48

• Proportion of CELs between groups

  week 96

• Rate of clinical relapses between groups

  week 48

• Rate of clinical relapses between groups

  week 96

• Time to switch to high efficacy treatments

  week 48

Other Outcomes (22)

• To estimate the best threshold of pNfL increase (last measure as compared to the mean of 2 previous measures) with best accuracy to detect evidence of disease activity

  week 96

• Time to evidence of disease activity using optimized threshold in experimental group

  week 96

• Correlation between basal pNfL fluctuations in patients with no evidence of disease activity and brain health questionnaire score

  week 96

Study Arms (2)

pNfL monitoring group

EXPERIMENTAL

Other: Monthly pNfL monitoring

Standard care

NO INTERVENTION

Interventions

Monthly pNfL monitoring OTHER

Monthly pNfL monitoring from blood samples. In case of \>50% pNfL increase as compared to the mean of the 2 previous measures, an unscheduled visit with brain and spinal cord MRI will be scheduled

pNfL monitoring group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient with RRMS according to 2017 McDonald's criteria.
• Less than 10 years from disease onset.
• Active RRMS (EDA) observed during the last 24 months: relapse and/or NELs and/or CELs as compared to a previous MRI performed within 24 months (± 3 months).
• MET (IFN, GA, TE, fumarates) for less than 24 months.
• Clinically stable disease for at least 30 days.
• Patients able to adhere to the study visit schedule.
• Patient must have signed and given the consent.
• Patient affiliated or beneficiary of a health insurance plan.

You may not qualify if:

• Pregnant or breastfeeding woman.
• Patient unable to perform brain and/or spinal cord MRI scans.
• Patient not willing to perform monthly blood punctures.
• Patient treated with HET (S1P agonists, natalizumab, ocrelizumab, ofatumumab, rituximab, alemtuzumab, cladribine, mitoxantrone).
• Patient with progressive MS.
• Patient unable to sign the consent.
• It is impossible to correctly inform the patient.
• Patient under judicial protection, or is an adult under guardianship.
• Female patients who are pregnant or breastfeeding or of reproductive potential who are not willing to employ effective birth control for the duration of the trial.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (2)

CHU de Nice

Nice, France

RECRUITING

CHU de Nîmes

Nîmes, France

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

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

Study Officials

• Eric Thouvenot

  Centre Hospitalier Universitaire de Nīmes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Thouvenot

CONTACT

04 66 68 32 61; eric.thouvenot@chu-nimes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 18, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

FR (2)