Multimodal Exploration of Patients With Multiple Sclerosis for an Early Detection of Subtle Progression
1 other identifier
interventional
60
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable multiple-sclerosis
Started Feb 2023
Typical duration for not_applicable multiple-sclerosis
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 14, 2023
CompletedFirst Submitted
Initial submission to the registry
May 15, 2023
CompletedFirst Posted
Study publicly available on registry
July 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedJuly 12, 2023
July 1, 2023
2.9 years
May 15, 2023
July 4, 2023
Conditions
Outcome Measures
Primary Outcomes (10)
Visual Evoked Potential (VEP)
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)
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)
To measure the integrity of motor pathways.
Change from baseline to 12 months
Tesla Brain MRI
Tesla Brain MRI (descriptive outcome)
Baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
6 months after baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
12 months after baseline
Epstein-Barr virus (EBV) serology (VCA IgG)
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)
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)
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
Study Arms (2)
PIRA
EXPERIMENTALFrom the MS functional outcome database, identification of a cohort of patients with RMS experiencing progression independent of relapse (PIRA)
N-PIRA
ACTIVE COMPARATORFrom the MS functional outcome database, identification of a cohort of patients with RMS not experiencing progression independent of relapse (N-PIRA)
Interventions
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.
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.
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.
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.
\- 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).
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).
Eligibility Criteria
You may qualify if:
- Patients ≥ 18-year-old with diagnosis of RMS according to 2017 McDonald diagnostic criteria
- 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
- Most recent functional outcome evaluation within 12 months of enrollment
- Availability of follow-up MRI data during the observational period
You may not qualify if:
- a) Contraindication to one or more of the paraclinical tests of the prospective multimodal evaluation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
CHU Brugmann
Brussels, 1020, Belgium
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Head of neurology department
Study Record Dates
First Submitted
May 15, 2023
First Posted
July 12, 2023
Study Start
February 14, 2023
Primary Completion
December 31, 2025
Study Completion
December 31, 2025
Last Updated
July 12, 2023
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will not share