Multiple SclerosisMYTH-MSNCT07545889
Multicenter Prospective Study Analyzing the Occurrence of Multiple Sclerosis Relapses Without Radiological Evidence: Myth or Reality?
A study testing Early Cerebro-spinal MRI, Biomarker Assessment and Clinical and Neuropsychological Evaluations in people with Multiple Sclerosis and RRMS, run by University Hospital, Strasbourg, France at 8 sites in France.
Trial summary
The MYTH-MS study is a multicenter prospective study investigating the occurrence of clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) in the absence of radiological activity on MRI. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis, RRMS, Multiple Sclerosis (MS) - Relapsing-remitting
- What is being tested?
- Early Cerebro-spinal MRI, Biomarker Assessment and Clinical and Neuropsychological Evaluations
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 8 sitesFrance
- Study dates
- 1 Sep 2026to 1 May 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult aged 18 to 70 years.
- Relapsing-Remitting Multiple Sclerosis according to the McDonald 2024 criteria.
- Patient receiving disease-modifying therapy (DMT) for multiple sclerosis.
- Most recent EDSS score between 0 and 7.0, dating back less than 1 year.
- Patient presenting with a neurological exacerbation lasting more than 24 hours and less than 7 days (excluding fatigue and pain alone).
- Patient capable of understanding the objectives and risks associated with the study and who has provided informed consent.
- Patient affiliated with or a beneficiary of a social security health insurance scheme.
Who cannot join
- Primary progressive or secondary progressive multiple sclerosis.
- Diagnosis of chronic psychotic disorder.
- Infection within the past week.
- Body temperature > 38.5°C at V0 (baseline visit).
- Corticosteroid bolus or plasma exchange in the month preceding inclusion.
- Chronic treatment with corticosteroids or immunosuppressants for another pathology.
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- Contraindication to MRI or gadolinium.
- Uncontrolled cardiac, renal, or hepatic pathology.
- Patient participating in another interventional study or still within an exclusion period.
- Pregnant or breastfeeding woman.
- Severe claustrophobia.
- Patient deprived of liberty (e.g., incarcerated).
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
France8 sites
Hospices Civils de Colmar
Colmar, 68024
François SELLAL, PH, +33 (0)3 89 12 41 50 ext. +33, francois.sellal@ch-colmar.fr
CHU de Dijon Bourgogne
Dijon, 21079
Thibault MOREAU, PU-PH, +33 (0)3 80 29 55 84 ext. +33, thibault.moreau@chu-dijon.fr
Centre Hospitalier de Haguenau
Haguenau, 67504
Sophie CARRE, PH, +33 (0)3.88.06.31.02 ext. +33, sophie.carre@ch-haguenau.fr
Chr Metz-Thionville
Metz, 57085
Basile WITTWER, PH, +33 (0)3 87 55 77 77 ext. +33, basile.wittwer@chr-metz-thionville.fr
Grpe Hosp Region Mulhouse & Sud Alsace
Mulhouse, 68051
Mathilde GOUDOT, PH, +33 (0)3 89 64 64 64 ext. +33, mathilde.goudot@ghrmsa.fr
CHU de Nancy
Nancy, 54035
Guillaume MATHEY, MCU-PH, +33 (0)3 83 85 16 88 ext. +33, G.MATHEY@chru-nancy.fr
Chu Reims
Reims, 51092
Sami, CCU-AH, +33 (0)3 26 78 70 75 ext. +33, sbenhammida@chu-reims.fr
Hôpitaux Universitaires de Strasbourg
Strasbourg, 67098
Kévin BIGAUT, MCU-PH, +33 (0)3 88 12 85 68 ext. +33, kevin.bigaut@chru-strasbourg.fr
About this study
The MYTH-MS study is a multicenter prospective study investigating the occurrence of clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) in the absence of radiological activity on MRI.
While MS relapses are typically associated with gadolinium-enhancing lesions on MRI, some patients present with acute neurological symptoms without radiological correlates, referred to as acute clinical events with stable MRI (ACES). The frequency, mechanisms, and clinical relevance of these events remain unclear due to limitations in previous studies.
Read more
The primary objective is to determine the proportion of RRMS patients experiencing a relapse without gadolinium-enhancing lesions on early brain and spinal MRI. Secondary objectives include identifying clinical, radiological, biological, and psychological predictors, assessing neurologists' diagnostic accuracy, and evaluating clinical outcomes such as disability, cognition, and quality of life over a 6-month follow-up.
A total of 136 patients with recent neurological exacerbations will be included. Each participant will undergo clinical assessment, cognitive and psychological evaluation, and early MRI, with follow-up at 6 months. An ancillary study will explore blood biomarkers (NfL, GFAP, and circulating DNA) to help differentiate true inflammatory relapses from ACES.
This study aims to improve the understanding and diagnosis of MS exacerbations and to optimize patient management by reducing misdiagnosis and unnecessary treatments.
Read the detailed description
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by relapses corresponding to episodes of new or worsening neurological symptoms. These relapses are typically associated with focal inflammatory activity detectable on magnetic resonance imaging (MRI) as gadolinium-enhancing lesions. However, in clinical practice, a subset of patients presents with symptoms suggestive of relapse without corresponding radiological findings, referred to as acute clinical events with stable MRI (ACES). The clinical significance, underlying mechanisms, and frequency of these events remain uncertain.
The MYTH-MS study is a multicenter, prospective cohort study designed to determine the proportion of patients with relapsing-remitting MS (RRMS) who experience a clinical relapse without gadolinium-enhancing lesions on early brain and spinal MRI. The study also aims to better characterize these events by identifying associated clinical, radiological, biological, and psychological factors.
Eligible participants are adults with RRMS presenting with recent neurological worsening suggestive of a relapse. At inclusion, patients will undergo standardized clinical evaluation, including neurological examination, disability assessment, cognitive testing, and patient-reported outcomes related to quality of life and psychological status. An early brain and spinal MRI with gadolinium injection will be performed within a defined time window following symptom onset.
The study will also assess the diagnostic performance of neurologists by comparing their clinical judgment regarding the presence of radiological activity and the likelihood of a true relapse versus a pseudo-relapse, along with their level of diagnostic confidence.
Participants will be followed for six months to evaluate clinical outcomes, including disability progression, cognitive performance, quality of life, and psychological parameters, and to assess the impact of relapse treatment according to MRI findings.
An ancillary biological study will be conducted to evaluate circulating biomarkers of neuronal and glial injury (e.g., neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], and circulating cell-free DNA). These biomarkers will be analyzed at baseline and follow-up to explore their potential role in distinguishing inflammatory relapses from ACES.
By providing a comprehensive characterization of MS exacerbations with and without radiological activity, this study aims to improve diagnostic accuracy, reduce uncertainty in clinical decision-making, and optimize therapeutic strategies in patients with RRMS.
- Being tested
- Early Cerebro-spinal MRI, Biomarker Assessment, Clinical and Neuropsychological Evaluations
- Keywords
- Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Acute Clinical Events with Stable MRI (ACES), Gadolinium-enhancing lesions, MRI-negative relapse, Functional Neurological Disorder, Pseudo-relapse
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Conversion Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early Cerebro-spinal MRIOther
A standardized MRI of the brain and spinal cord with gadolinium injection. Performed very early during an acute neurological exacerbation, specifically between Day 0 and Day 6 (J0 to J6).
To detect the presence or absence of gadolinium-enhancing lesions, which is the study's primary endpoint.
Includes Susceptibility Weighted Imaging (SWI) to look for paramagnetic rim lesions and post-gadolinium FLAIR sequences to detect leptomeningeal enhancement.
Biomarker AssessmentDiagnostic test
Also called biological markers, NfL, GFAP, and cfDNA
Routine blood and urine tests, including CRP, blood count, and urinalysis (leukocytes, nitrites) to rule out infections that could cause a pseudo-relapse.
Ancillary Study Biomarkers: For consenting patients, blood samples are collected to measure specific molecular markers:
NfL (Neurofilaments): A marker of axonal damage. GFAP (Glial Fibrillary Acidic Protein): A marker of astrocytic activation. cfDNA (Cell-free DNA): Used to assess cellular stress or death
Clinical and Neuropsychological EvaluationsDiagnostic test
Standardized Scales:
- EDSS (Expanded Disability Status Scale): Used to measure the degree of neurological disability at inclusion and at the 6-month follow-up.
- SDMT (Symbol Digit Modalities Test) and CSCT (Computerized Speed Cognitive Test): Used to assess cognitive processing speed.
Functional Disorder Screening: A specific clinical examination is conducted to identify positive signs of Functional Neurological Disorders (FND/TNF), which may mimic a relapse.
| Study group | Role | What they receive |
|---|---|---|
| RRMS Patients with Acute Neurological Exacerbations | Experimental | Not described Receives: Other: Early Cerebro-spinal MRI; Diagnostic Test: Biomarker Assessment; Diagnostic Test: Clinical and Neuropsychological Evaluations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of RRMS Patients with Absence or Presence of Gadolinium-Enhancing Lesion(s) on Brain and Spinal Cord MRI
This measure evaluates the frequency of "Acute Clinical Events with Stable MRI" (ACES). Participants undergo a standardized MRI of the brain and spinal cord using gadolinium contrast medium within a strict window of 0 to 6 days following the onset of a suspected neurological relapse.
The primary finding is defined as the absence of any gadolinium-enhancing lesions (which indicate active inflammation) despite the presence of clinical symptoms. Data is reported as the percentage of the total cohort meeting these criteria, assessed through a centralized radiological review using a standardized reading grid. This allows for a precise characterization of clinical relapses that lack immediate radiological confirmation.
Measured: performed between Day 0 and Day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study start1 Sep 2026 (estimated)
- Primary completion7 Sep 2029 (estimated)
- Study completion1 May 2030 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07545889
- Sponsor's protocol ID
- RC25_0053
- Acronym
- MYTH-MS
- Status last verified
- Apr 2026
- First submitted
- 15 Apr 2026
- Last updated
- 22 Apr 2026
- 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 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Prospective Study Analyzing the Occurrence of Multiple Sclerosis Relapses Without Radiological Evidence: Myth or Reality?
- ClinicalTrials.gov ID
- NCT07545889
- Acronym / sponsor ID
- MYTH-MS / RC25_0053
- Keywords
- Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Acute Clinical Events with Stable MRI (ACES), Gadolinium-enhancing lesions, MRI-negative relapse, Functional Neurological Disorder, Pseudo-relapse
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 7 Sep 2029 (estimated)
- Study completion
- 1 May 2030 (estimated)
- First posted
- 22 Apr 2026 (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.
The MYTH-MS study is a multicenter prospective study investigating the occurrence of clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) in the absence of radiological activity on MRI.
While MS relapses are typically associated with gadolinium-enhancing lesions on MRI, some patients present with acute neurological symptoms without radiological correlates, referred to as acute clinical events with stable MRI (ACES). The frequency, mechanisms, and clinical relevance of these events remain unclear due to limitations in previous studies.
The primary objective is to determine the proportion of RRMS patients experiencing a relapse without gadolinium-enhancing lesions on early brain and spinal MRI. Secondary objectives include identifying clinical, radiological, biological, and psychological predictors, assessing neurologists' diagnostic accuracy, and evaluating clinical outcomes such as disability, cognition, and quality of life over a 6-month follow-up.
A total of 136 patients with recent neurological exacerbations will be included. Each participant will undergo clinical assessment, cognitive and psychological evaluation, and early MRI, with follow-up at 6 months. An ancillary study will explore blood biomarkers (NfL, GFAP, and circulating DNA) to help differentiate true inflammatory relapses from ACES.
This study aims to improve the understanding and diagnosis of MS exacerbations and to optimize patient management by reducing misdiagnosis and unnecessary treatments.
Detailed description
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by relapses corresponding to episodes of new or worsening neurological symptoms. These relapses are typically associated with focal inflammatory activity detectable on magnetic resonance imaging (MRI) as gadolinium-enhancing lesions. However, in clinical practice, a subset of patients presents with symptoms suggestive of relapse without corresponding radiological findings, referred to as acute clinical events with stable MRI (ACES). The clinical significance, underlying mechanisms, and frequency of these events remain uncertain.
The MYTH-MS study is a multicenter, prospective cohort study designed to determine the proportion of patients with relapsing-remitting MS (RRMS) who experience a clinical relapse without gadolinium-enhancing lesions on early brain and spinal MRI. The study also aims to better characterize these events by identifying associated clinical, radiological, biological, and psychological factors.
Eligible participants are adults with RRMS presenting with recent neurological worsening suggestive of a relapse. At inclusion, patients will undergo standardized clinical evaluation, including neurological examination, disability assessment, cognitive testing, and patient-reported outcomes related to quality of life and psychological status. An early brain and spinal MRI with gadolinium injection will be performed within a defined time window following symptom onset.
The study will also assess the diagnostic performance of neurologists by comparing their clinical judgment regarding the presence of radiological activity and the likelihood of a true relapse versus a pseudo-relapse, along with their level of diagnostic confidence.
Participants will be followed for six months to evaluate clinical outcomes, including disability progression, cognitive performance, quality of life, and psychological parameters, and to assess the impact of relapse treatment according to MRI findings.
An ancillary biological study will be conducted to evaluate circulating biomarkers of neuronal and glial injury (e.g., neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], and circulating cell-free DNA). These biomarkers will be analyzed at baseline and follow-up to explore their potential role in distinguishing inflammatory relapses from ACES.
By providing a comprehensive characterization of MS exacerbations with and without radiological activity, this study aims to improve diagnostic accuracy, reduce uncertainty in clinical decision-making, and optimize therapeutic strategies in patients with RRMS.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RRMS Patients with Acute Neurological Exacerbations | Experimental | Other: Early Cerebro-spinal MRI, Diagnostic Test: Biomarker Assessment, Diagnostic Test: Clinical and Neuropsychological Evaluations |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult aged 18 to 70 years.
- Relapsing-Remitting Multiple Sclerosis according to the McDonald 2024 criteria.
- Patient receiving disease-modifying therapy (DMT) for multiple sclerosis.
- Most recent EDSS score between 0 and 7.0, dating back less than 1 year.
- Patient presenting with a neurological exacerbation lasting more than 24 hours and less than 7 days (excluding fatigue and pain alone).
Key exclusion criteria (12 listed)
- Primary progressive or secondary progressive multiple sclerosis.
- Diagnosis of chronic psychotic disorder.
- Infection within the past week.
- Body temperature > 38.5°C at V0 (baseline visit).
- Corticosteroid bolus or plasma exchange in the month preceding inclusion.
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 |
|---|---|---|
| Early Cerebro-spinal MRIA standardized MRI of the brain and spinal cord with gadolinium injection. Performed very early during an acute neurological exacerbation, specifically between Day 0 and Day 6 (J0 to J6). To detect the presence or absence of gadolinium-enhancing lesions, which is the study's primary endpoint. Includes Susceptibility Weighted Imaging (SWI) to look for paramagnetic rim lesions and post-gadolinium FLAIR sequences to detect leptomeningeal enhancement. | Other | RRMS Patients with Acute Neurological Exacerbations |
| Biomarker AssessmentAlso: biological markers, NfL, GFAP, and cfDNARoutine blood and urine tests, including CRP, blood count, and urinalysis (leukocytes, nitrites) to rule out infections that could cause a pseudo-relapse. Ancillary Study Biomarkers: For consenting patients, blood samples are collected to measure specific molecular markers: NfL (Neurofilaments): A marker of axonal damage. GFAP (Glial Fibrillary Acidic Protein): A marker of astrocytic activation. cfDNA (Cell-free DNA): Used to assess cellular stress or death | Diagnostic test | RRMS Patients with Acute Neurological Exacerbations |
| Clinical and Neuropsychological EvaluationsStandardized Scales: * EDSS (Expanded Disability Status Scale): Used to measure the degree of neurological disability at inclusion and at the 6-month follow-up. * SDMT (Symbol Digit Modalities Test) and CSCT (Computerized Speed Cognitive Test): Used to assess cognitive processing speed. Functional Disorder Screening: A specific clinical examination is conducted to identify positive signs of Functional Neurological Disorders (FND/TNF), which may mimic a relapse. | Diagnostic test | RRMS Patients with Acute Neurological Exacerbations |
Primary outcome
Proportion of RRMS Patients with Absence or Presence of Gadolinium-Enhancing Lesion(s) on Brain and Spinal Cord MRI
Time frame: performed between Day 0 and Day 6
This measure evaluates the frequency of "Acute Clinical Events with Stable MRI" (ACES). Participants undergo a standardized MRI of the brain and spinal cord using gadolinium contrast medium within a strict window of 0 to 6 days following the onset of a suspected neurological relapse. The primary finding is defined as the absence of any gadolinium-enhancing lesions (which indicate active inflammation) despite the presence of clinical symptoms. Data is reported as the percentage of the total cohort meeting these criteria, assessed through a centralized radiological review using a standardized reading grid. This allows for a precise characterization of clinical relapses that lack immediate radiological confirmation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- 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.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early Cerebro-spinal MRI, Biomarker Assessment and Clinical and Neuropsychological Evaluations in people with Multiple Sclerosis and RRMS, run by University Hospital, Strasbourg, France at 8 sites in France.
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 7 inclusion and 12 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: opening soon, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kévin BIGAUT, MCU-PH (+33 (0)3 88 12 85 68 ext. +33, kevin.bigaut@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of RRMS Patients with Absence or Presence of Gadolinium-Enhancing Lesion(s) on Brain and Spinal Cord MRI (time frame: performed between Day 0 and Day 6). 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 22 Apr 2026.