Multiple SclerosisNCT05941975
Multimodal Exploration of Patients With Multiple Sclerosis for an Early Detection of Subtle Progression
A study testing Visual Evoked Potential (VEP), Somatosensory evoked potential (SSEP) and Transcranial magnetic motor evoked potentials (TCmMEP) in people with Multiple Sclerosis, run by Brugmann University Hospital at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Visual Evoked Potential (VEP), Somatosensory evoked potential (SSEP) and Transcranial magnetic motor evoked potentials (TCmMEP)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- 14 Feb 2023to 31 Dec 2025
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Contraindication to one or more of the paraclinical tests of the prospective multimodal evaluation
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
CHU Brugmann
Brussels, 1020
Bernard Dachy, MD, 32 2 4772446, Bernard.DACHY@chu-brugmann.be
About this study
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.
Read more
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.
- Conditions
- Multiple Sclerosis
- Being tested
- Visual Evoked Potential (VEP), Somatosensory evoked potential (SSEP), Transcranial magnetic motor evoked potentials (TCmMEP), Tesla Brain MRI, Blood test - Neurofilament light chain (NfL)
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Visual Evoked Potential (VEP)Device
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.
Somatosensory evoked potential (SSEP)Device
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.
Transcranial magnetic motor evoked potentials (TCmMEP)Device
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.
Tesla Brain MRIDevice
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.
Blood test - Neurofilament light chain (NfL)Diagnostic test
- 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).
Blood test - EBV serologyDiagnostic test
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).
| Study group | Role | What they receive |
|---|---|---|
| PIRA | Experimental | From the MS functional outcome database, identification of a cohort of patients with RMS experiencing progression independent of relapse (PIRA) Receives: Device: Visual Evoked Potential (VEP); Device: Somatosensory evoked potential (SSEP); Device: Transcranial magnetic motor evoked potentials (TCmMEP); Device: Tesla Brain MRI; Diagnostic Test: Blood test - Neurofilament light chain (NfL); Diagnostic Test: Blood test - EBV serology |
| N-PIRA | Active comparator | From the MS functional outcome database, identification of a cohort of patients with RMS not experiencing progression independent of relapse (N-PIRA) Receives: Device: Visual Evoked Potential (VEP); Device: Somatosensory evoked potential (SSEP); Device: Transcranial magnetic motor evoked potentials (TCmMEP); Device: Tesla Brain MRI; Diagnostic Test: Blood test - Neurofilament light chain (NfL); Diagnostic Test: Blood test - EBV serology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Evoked Potential (VEP)
To assess the integrity of visual pathways through the optic nerves to the visual cortex.
Measured: 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.
Measured: Change from baseline to 12 months
Transcranial magnetic motor evoked potentials (TCmMEP)
To measure the integrity of motor pathways.
Measured: Change from baseline to 12 months
Tesla Brain MRI
Tesla Brain MRI (descriptive outcome)
Measured: Baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Measured: Baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Measured: 6 months after baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 12 months after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2023
- Study start14 Feb 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brugmann University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernard Dachy, Brugmann University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05941975
- Sponsor's protocol ID
- CHUB-PIRA
- Status last verified
- Jul 2023
- First submitted
- 15 May 2023
- Last updated
- 12 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Exploration of Patients With Multiple Sclerosis for an Early Detection of Subtle Progression
- ClinicalTrials.gov ID
- NCT05941975
- Acronym / sponsor ID
- CHUB-PIRA
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Brugmann University HospitalUniversity, hospital or other
- Study start
- 14 Feb 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 12 Jul 2023 (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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PIRA | Experimental | Device: Visual Evoked Potential (VEP), Device: Somatosensory evoked potential (SSEP), Device: Transcranial magnetic motor evoked potentials (TCmMEP), Device: Tesla Brain MRI, Diagnostic Test: Blood test - Neurofilament light chain (NfL), Diagnostic Test: Blood test - EBV serologyFrom the MS functional outcome database, identification of a cohort of patients with RMS experiencing progression independent of relapse (PIRA) |
| N-PIRA | Active comparator | Device: Visual Evoked Potential (VEP), Device: Somatosensory evoked potential (SSEP), Device: Transcranial magnetic motor evoked potentials (TCmMEP), Device: Tesla Brain MRI, Diagnostic Test: Blood test - Neurofilament light chain (NfL), Diagnostic Test: Blood test - EBV serologyFrom the MS functional outcome database, identification of a cohort of patients with RMS not experiencing progression independent of relapse (N-PIRA) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- Contraindication to one or more of the paraclinical tests of the prospective multimodal evaluation
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 |
|---|---|---|
| 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 | N-PIRA, PIRA |
| 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 | N-PIRA, PIRA |
| 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 | N-PIRA, PIRA |
| Tesla Brain MRIAll 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. | Device | N-PIRA, PIRA |
| 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 | N-PIRA, PIRA |
| Blood test - EBV serologyEBV 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). | Diagnostic test | N-PIRA, PIRA |
Primary outcome
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.
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.
Transcranial magnetic motor evoked potentials (TCmMEP)
Time frame: Change from baseline to 12 months
To measure the integrity of motor pathways.
Tesla Brain MRI
Time frame: Baseline
Tesla Brain MRI (descriptive outcome)
Neurofilament light chain (NfL) serum levels
Time frame: Baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Time frame: 6 months after baseline
Neurofilament light chain (NfL) serum levels
Neurofilament light chain (NfL) serum levels
Time frame: 12 months after baseline
Neurofilament light chain (NfL) serum levels
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).
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).
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2023.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Visual Evoked Potential (VEP), Somatosensory evoked potential (SSEP) and Transcranial magnetic motor evoked potentials (TCmMEP) in people with Multiple Sclerosis, run by Brugmann University Hospital at 1 site in Belgium.
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 4 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: status not confirmed, as of the sponsor's last update on 12 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vito Tota (3224772446, Vito.TOTA@chu-brugmann.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Evoked Potential (VEP) (time frame: Change from baseline to 12 months). The study lists 10 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 12 Jul 2023.