Multimodal Exploration of Patients With Multiple Sclerosis for an Early Detection of Subtle Progression

July 4, 2023 updated by: Bernard Dachy, Brugmann University Hospital

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS), characterized by a complex interplay of inflammatory demyelination and neuronal damage. The core MS phenotypes defined by clinical course are the relapsing and the progressive forms.Relapsing MS (RMS) is characterized by attacks - also called relapses - defined as new or increasing neurologic dysfunction, followed by periods of partial or complete recovery, without apparent progression of the disease during the periods of remission. In contrast, progressive MS (PMS) is characterized by progressive worsening of neurologic function leading to accumulation of disability over time independent of relapses. Additional descriptors ("active/not-active") serve to better characterize the presence of clinical and/or radiological activity both in relapsing and progressive forms.

In recent years, the concept of a silent progression, also known as smouldering MS, is making its way into the common lexicon of MS experts, challenging the current definitions of MS phenotypes. A growing body of literature suggests that the line between RMS and PMS is not as marked as men thought, and that inflammation and neurodegeneration can represent a single disease continuum coexisting early on in the disease course. Whilst it is established that relapse-associated worsening (RAW) can be accounted for by an acute inflammatory focal damage leading to axonal transection and conduction block, the physiopathology underlying the progression independent of relapse activity (PIRA) remains unclear.

It is becoming apparent that there is an increasing need for a personalized therapeutic approach by considering the individual MS phenotype of each patient, thereby enabling the choice of the molecule best suited to counteract the predominant disease pattern of that individual patient.

There is a limited number of studies combining clinical scores, neurophysiological evaluation and neuroimaging in patients with MS experiencing PIRA. Integrating a multimodal exploration of these patients might allow a step forward in the early recognition, management, and treatment of disability accumulation independent from relapses in patients with MS.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients ≥ 18-year-old with diagnosis of RMS according to 2017 McDonald diagnostic criteria
  2. Availability in the functional outcome database of at least 3 time-point complete evaluations with a time frame from the first to the last evaluation of minimum 12 months
  3. Most recent functional outcome evaluation within 12 months of enrollment
  4. Availability of follow-up MRI data during the observational period

Exclusion Criteria:

a) Contraindication to one or more of the paraclinical tests of the prospective multimodal evaluation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PIRA
From the MS functional outcome database, identification of a cohort of patients with RMS experiencing progression independent of relapse (PIRA)
Device: Visual Evoked Potential (VEP)
To assess the integrity of visual pathways through the optic nerves to the visual cortex, latencies and amplitudes of P100 will be measured after pattern-reversal stimuli.
Device: Somatosensory evoked potential (SSEP)
To assess the integrity of sensitive pathways through the peripheral nerves and dorsal spinal cord to the somatosensory cortex. For the upper limbs, latencies and amplitudes of N9, N13, P14, N20 and P25 will be measured after median nerve stimulation. For the lower limbs, latency and amplitude of P40 will be measured after tibial nerve stimulation.
Device: Transcranial magnetic motor evoked potentials (TCmMEP)
To measure the integrity of motor pathways, the central conduction times will be measured for upper and lower limbs through magnetic stimulations of the primary motor cortex and the spinal cord, at cervical and lumbar levels.
Device: Tesla Brain MRI
All patients will undergo a single brain MRI on a 3T scanner. The acquisition protocol will include high-resolution three-dimensional (3D) T2*-weighted echo-planar imaging and 3D T2-FLAIR images acquired, respectively, during or after intravenous injection of a single dose (0.1mmol/kg) of gadolinium-based contrast material.
Diagnostic test: Blood test - Neurofilament light chain (NfL)
- Neurofilament light chain (NfL) will be tested (Quanterix's Simoa® Technology) in the serum of patients. To evaluate their variation over time, 3 time-point tests will be obtained at 6 months apart (at baseline, at 6- and 12-month follow-up).
Diagnostic test: Blood test - EBV serology
EBV serology will be assessed (VCA IgG) in the serum of patients to evaluate the variation of antibody titers over time (at baseline, at 6- and 12-month follow-up), and compare to titers at the time of diagnosis (when available in their medical record).
Active Comparator: N-PIRA
From the MS functional outcome database, identification of a cohort of patients with RMS not experiencing progression independent of relapse (N-PIRA)
Device: Visual Evoked Potential (VEP)
To assess the integrity of visual pathways through the optic nerves to the visual cortex, latencies and amplitudes of P100 will be measured after pattern-reversal stimuli.
Device: Somatosensory evoked potential (SSEP)
To assess the integrity of sensitive pathways through the peripheral nerves and dorsal spinal cord to the somatosensory cortex. For the upper limbs, latencies and amplitudes of N9, N13, P14, N20 and P25 will be measured after median nerve stimulation. For the lower limbs, latency and amplitude of P40 will be measured after tibial nerve stimulation.
Device: Transcranial magnetic motor evoked potentials (TCmMEP)
To measure the integrity of motor pathways, the central conduction times will be measured for upper and lower limbs through magnetic stimulations of the primary motor cortex and the spinal cord, at cervical and lumbar levels.
Device: Tesla Brain MRI
All patients will undergo a single brain MRI on a 3T scanner. The acquisition protocol will include high-resolution three-dimensional (3D) T2*-weighted echo-planar imaging and 3D T2-FLAIR images acquired, respectively, during or after intravenous injection of a single dose (0.1mmol/kg) of gadolinium-based contrast material.
Diagnostic test: Blood test - Neurofilament light chain (NfL)
- Neurofilament light chain (NfL) will be tested (Quanterix's Simoa® Technology) in the serum of patients. To evaluate their variation over time, 3 time-point tests will be obtained at 6 months apart (at baseline, at 6- and 12-month follow-up).
Diagnostic test: Blood test - EBV serology
EBV serology will be assessed (VCA IgG) in the serum of patients to evaluate the variation of antibody titers over time (at baseline, at 6- and 12-month follow-up), and compare to titers at the time of diagnosis (when available in their medical record).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual Evoked Potential (VEP)
Time Frame: Change from baseline to 12 months
To assess the integrity of visual pathways through the optic nerves to the visual cortex.
Change from baseline to 12 months
Somatosensory evoked potential (SSEP)
Time Frame: Change from baseline to 12 months
To assess the integrity of sensitive pathways through the peripheral nerves and dorsal spinal cord to the somatosensory cortex.
Change from baseline to 12 months
Transcranial magnetic motor evoked potentials (TCmMEP)
Time Frame: Change from baseline to 12 months
To measure the integrity of motor pathways.
Change from baseline to 12 months
Tesla Brain MRI
Time Frame: Baseline
Tesla Brain MRI (descriptive outcome)
Baseline
Neurofilament light chain (NfL) serum levels
Time Frame: Baseline
Neurofilament light chain (NfL) serum levels
Baseline
Neurofilament light chain (NfL) serum levels
Time Frame: 6 months after baseline
Neurofilament light chain (NfL) serum levels
6 months after baseline
Neurofilament light chain (NfL) serum levels
Time Frame: 12 months after baseline
Neurofilament light chain (NfL) serum levels
12 months after baseline
Epstein-Barr virus (EBV) serology (VCA IgG)
Time Frame: Baseline
EBV serology will be assessed (VCA IgG) in the serum of patients to evaluate the variation of antibody titers over time (at baseline, at 6- and 12-month follow-up), and compare to titers at the time of diagnosis (when available in their medical record).
Baseline
Epstein-Barr virus (EBV) serology (VCA IgG)
Time Frame: 6 months after baseline
EBV serology will be assessed (VCA IgG) in the serum of patients to evaluate the variation of antibody titers over time (at baseline, at 6- and 12-month follow-up), and compare to titers at the time of diagnosis (when available in their medical record).
6 months after baseline
Epstein-Barr virus (EBV) serology (VCA IgG)
Time Frame: 12 months after baseline
EBV serology will be assessed (VCA IgG) in the serum of patients to evaluate the variation of antibody titers over time (at baseline, at 6- and 12-month follow-up), and compare to titers at the time of diagnosis (when available in their medical record).
12 months after baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brugmann University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 14, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 15, 2023

First Submitted That Met QC Criteria

July 4, 2023

First Posted (Actual)

July 12, 2023

Study Record Updates

Last Update Posted (Actual)

July 12, 2023

Last Update Submitted That Met QC Criteria

July 4, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUB-PIRA

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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