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

CHU Brugmann University Hospital

Status: Enrolling

Conditions: Multiple Sclerosis

Treatments: Device: Somatosensory evoked potential (SSEP); Device: Visual Evoked Potential (VEP); Device: Transcranial magnetic motor evoked potentials (TCmMEP); Diagnostic Test: Blood test - Neurofilament light chain (NfL); Device: Tesla Brain MRI; Diagnostic Test: Blood test - EBV serology

Study type: Interventional

Funder types: Other

Identifiers

NCT05941975

CHUB-PIRA

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

PIRA

Experimental group

Description:

From the MS functional outcome database, identification of a cohort of patients with RMS experiencing progression independent of relapse (PIRA)

Treatment:

Diagnostic Test: Blood test - Neurofilament light chain (NfL)

Diagnostic Test: Blood test - EBV serology

Device: Transcranial magnetic motor evoked potentials (TCmMEP)

Device: Tesla Brain MRI

Device: Somatosensory evoked potential (SSEP)

Device: Visual Evoked Potential (VEP)

N-PIRA

Active Comparator group

Description:

From the MS functional outcome database, identification of a cohort of patients with RMS not experiencing progression independent of relapse (N-PIRA)

Treatment:

Diagnostic Test: Blood test - Neurofilament light chain (NfL)

Diagnostic Test: Blood test - EBV serology

Device: Transcranial magnetic motor evoked potentials (TCmMEP)

Device: Tesla Brain MRI

Device: Somatosensory evoked potential (SSEP)

Device: Visual Evoked Potential (VEP)