Multiple SclerosisMSpineNCT06827834
Spinal Cord Monitoring in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by Zuyderland Medisch Centrum at 5 sites in Netherlands.
Trial summary
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young adults. Magnetic resonance imaging (MRI) is the most important paraclinical investigation used in the diagnosis and monitoring of the disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 155 participants
- Where
- 5 sitesNetherlands
- Study dates
- 6 Aug 2024to 1 Jun 2028
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Population of treatment-naïve relapsing-remitting MS patients, early in the disease course (within 5 years of first clinical event) between 18 - 65 years old, where a first DMT is initiated.
Who may be able to join
- Patients between 18 and 65 years old
- Patients diagnosed with relapsing-remitting MS (≤5 years of first clinical event)
- Treatment-naïve patients starting (currently in the Netherlands approved) DMT
Who cannot join
- Patients who presented first clinical event more than five years ago
- Patients who have already started DMT
- Patients who are incapable of giving informed consent
- Patients who are unable to undergo local MRI scan, due to for instance
- Physical problems, for instance due to size/obesity (not fitting in regular MRI scanner), not being able to lie flat for extended periods of time (e.g. due to pain, shortness of breath)
- Due to claustrophobia
Show all 9Show fewer
- Patients who have contraindications for MRI scan, for instance
- Due to MRI-unsafe or non-compatible implanted material/devices, such as pacemakers or ocular metal splinters
- Patients who are pregnant at inclusion
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Not yet recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, North Brabant, 5223GZ
Jeroen van Eijk, +31735532325, j.eijkvan@jbz.nl
Jeroen van Eijk
- Not yet recruiting
Rijnstate
Arnhem, Gelderland, 6815AD
Tom Olde Dubbelink, +31880058888, toldedubbelink@rijnstate.nl
Tom Olde Dubbelink
- Recruiting
Albert Schweitzer ziekenhuis
Dordrecht, South Holland, 3318AT
Janet de Beukelaar, +31786541111, beukelaarj@asz.nl
Janet de Beukelaar
- Recruiting
Zuyderland Medisch Centrum
Geleen, Limburg, 6162BG
Demmie Bouweriks, MD, +31884597603, d.bouweriks@zuyderland.nl
Oliver Gerlach
- Not yet recruiting
Erasmus MC
Rotterdam, South Holland, 3015GD
Joost Smolders, +31107040130, j.j.f.m.smolders@erasmusmc.nl
Joost Smolders
About this study
Official title: A Prospective Longitudinal Study of Spinal Cord Lesions in Multiple Sclerosis: MRI Monitoring and Prognostic Factors for Active Disease
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young adults. Magnetic resonance imaging (MRI) is the most important paraclinical investigation used in the diagnosis and monitoring of the disease. In the past years, spinal cord MRI has improved significantly and has become an important part of the diagnostic workup for MS. Presently, follow-up imaging of the spinal cord is only performed when spinal cord related symptoms occur. However, there is increasing evidence that asymptomatic spinal cord lesions can occur, independently of brain disease activity. Despite these cord lesions being asymptomatic, they impact disability accrual in the long term. Although this might be an imaging marker for monitoring and treatment, it is not yet applied in the clinical setting.
The investigators will prospectively collect spinal cord MRI data (in addition to routine brain MRI), and blood-based biomarkers (plus cerebral spinal fluid markers, if available), in recently diagnosed MS patients, to address the following research questions:
- What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
- And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
- A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.
Read the detailed description
The investigators aim to prospectively collect spinal cord MRI data (in addition to routine brain MRI), in recently diagnosed MS patients, to address the following research questions:
What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
- What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
- In the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
Hypothesis: The hypothesis is that the detected incidence of asymptomatic cord lesions independent of brain MRI activity will be higher than the approximately 10% per year reported in retrospective studies.
A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.
- What subgroups are prone to new spinal cord lesions at follow-up in early disease? In particular:
- Can disease activity on spinal cord MRI be predicted by baseline CSF profiles, i.e. is there an association between intrathecal IgM/IgG synthesis, number of oligoclonal bands and/or kappa free light chains at baseline and formation of new spinal cord lesions at follow-up?
- Is there an association between low number of transitional B cells in blood at baseline and formation of new spinal cord lesions?
- Is there an association between soluble blood markers and other blood biomarkers at baseline and formation of new spinal cord lesions at follow-up?
- What subtype of clinical presentation or certain physical complaints are associated with new spinal cord lesions during follow-up?
Hypothesis: The hypothesis is that more new spinal cord lesions occur in patients with CSF profile positive for intrathecal IgM, IgG synthesis and higher number oligoclonal bands, a low number of transitional B cells at baseline, a low number of CD56bright NK cells, high levels of activating sICPs and low levels of inhibitory sICPs at baseline, and/or a presenting syndrome of optic neuritis or myelitis.
To investigate the research questions, MS patients will be enrolled from five Dutch MS centres in an observational study with a follow-up of 27 months. Patients will be asked to participate when they are being screened for DMT initiation and given 7 days to consider. Informed consent will be obtained by a doctor, part of the research team. Next to routine regular follow-up with brain MRI and outpatient clinic visits, patients will receive spinal cord MRI and a structured registration of clinical parameters and collection of blood samples. Towards the end of follow-up, it will be evaluated whether starting an extension study is of additional value.
- Conditions
- Multiple Sclerosis
- Keywords
- spinal cord, mri, biomarkers, multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Spinal cord lesion count
Measured: 27 months
Secondary outcomes (7)
Brain MRI acitivity
Number of new (new T2, T1 gadolinium-enhancing) and expanding lesions
Measured: 27 months
Expanded disability status scale (EDSS)
Measured at 3, 15 and 27 months
Measured: 27 months
Timed 25 foot walk test
Measured at 3, 15 and 27 months
Measured: 27 months
Nine hole peg test
Measured at 3, 15 and 27 months
Measured: 27 months
No evidence of disease activity
Composite outcome: no relapses, no progression independent of relapse activity, no new lesions on brain or spinal cord MRI
Measured: 27 months
Biomarkers neuronal damage
Neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAP)
Measured: 27 months
Lower urinary tract symptoms
- For females: International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Module (ICIQ-FLUTS)
- For males: International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS)
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2025
- Study start6 Aug 2024
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zuyderland Medisch Centrum
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06827834
- Sponsor's protocol ID
- Z2023148
- Acronym
- MSpine
- Status last verified
- Jan 2025
- First submitted
- 27 Jan 2025
- Last updated
- 14 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Di Sabatino E, Gaetani L, Sperandei S, Fiacca A, Guercini G, Parnetti L, Di Filippo M. The no evidence of disease activity (NEDA) concept in MS: impact of spinal cord MRI. J Neurol. 2022 Jun;269(6):3129-3135. doi: 10.1007/s00415-021-10901-2. Epub 2021 Nov 24.
PubMed 34820734Kreiter D, Spee R, Merry A, Hupperts R, Gerlach O. Effect of disease-modifying treatment on spinal cord lesion formation in multiple sclerosis: A retrospective observational study. Mult Scler Relat Disord. 2023 Nov;79:104994. doi: 10.1016/j.msard.2023.104994. Epub 2023 Sep 4.
PubMed 37683557Brownlee WJ, Altmann DR, Alves Da Mota P, Swanton JK, Miszkiel KA, Wheeler-Kingshott CG, Ciccarelli O, Miller DH. Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome. Mult Scler. 2017 Apr;23(5):665-674. doi: 10.1177/1352458516663034. Epub 2016 Aug 6.
PubMed 27481210Granella F, Tsantes E, Graziuso S, Bazzurri V, Crisi G, Curti E. Spinal cord lesions are frequently asymptomatic in relapsing-remitting multiple sclerosis: a retrospective MRI survey. J Neurol. 2019 Dec;266(12):3031-3037. doi: 10.1007/s00415-019-09526-3. Epub 2019 Sep 7.
PubMed 31494713Zecca C, Disanto G, Sormani MP, Riccitelli GC, Cianfoni A, Del Grande F, Pravata E, Gobbi C. Relevance of asymptomatic spinal MRI lesions in patients with multiple sclerosis. Mult Scler. 2016 May;22(6):782-91. doi: 10.1177/1352458515599246. Epub 2015 Oct 12.
PubMed 26459149Bouweriks D, Kreiter D, Knippenberg SAM, Damoiseaux JGMC, Smolders J, van Eijk JJJ, Mommers EHH, de Beukelaar JWK, Olde Dubbelink TBG, Merry AHH, Hupperts RMM, Gerlach OHH. MSpine: a prospective longitudinal study of spinal cord lesions in multiple sclerosis: MRI monitoring and prognostic factors for active disease. A study protocol. Neurol Res Pract. 2026 Apr 17;8(1):23. doi: 10.1186/s42466-026-00465-9.
PubMed 41998718
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Longitudinal Study of Spinal Cord Lesions in Multiple Sclerosis: MRI Monitoring and Prognostic Factors for Active Disease
- ClinicalTrials.gov ID
- NCT06827834
- Acronym / sponsor ID
- MSpine / Z2023148
- Conditions
- Multiple Sclerosis
- Keywords
- spinal cord, mri, biomarkers, multiple sclerosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Zuyderland Medisch CentrumUniversity, hospital or other
- Study start
- 6 Aug 2024 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 14 Feb 2025 (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 the most common demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young adults. Magnetic resonance imaging (MRI) is the most important paraclinical investigation used in the diagnosis and monitoring of the disease. In the past years, spinal cord MRI has improved significantly and has become an important part of the diagnostic workup for MS. Presently, follow-up imaging of the spinal cord is only performed when spinal cord related symptoms occur. However, there is increasing evidence that asymptomatic spinal cord lesions can occur, independently of brain disease activity. Despite these cord lesions being asymptomatic, they impact disability accrual in the long term. Although this might be an imaging marker for monitoring and treatment, it is not yet applied in the clinical setting.
The investigators will prospectively collect spinal cord MRI data (in addition to routine brain MRI), and blood-based biomarkers (plus cerebral spinal fluid markers, if available), in recently diagnosed MS patients, to address the following research questions:
- What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
- And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
- A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.
Detailed description
The investigators aim to prospectively collect spinal cord MRI data (in addition to routine brain MRI), in recently diagnosed MS patients, to address the following research questions:
What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
- What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
- In the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
Hypothesis: The hypothesis is that the detected incidence of asymptomatic cord lesions independent of brain MRI activity will be higher than the approximately 10% per year reported in retrospective studies.
A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.
- What subgroups are prone to new spinal cord lesions at follow-up in early disease? In particular:
- Can disease activity on spinal cord MRI be predicted by baseline CSF profiles, i.e. is there an association between intrathecal IgM/IgG synthesis, number of oligoclonal bands and/or kappa free light chains at baseline and formation of new spinal cord lesions at follow-up?
- Is there an association between low number of transitional B cells in blood at baseline and formation of new spinal cord lesions?
- Is there an association between soluble blood markers and other blood biomarkers at baseline and formation of new spinal cord lesions at follow-up?
- What subtype of clinical presentation or certain physical complaints are associated with new spinal cord lesions during follow-up?
Hypothesis: The hypothesis is that more new spinal cord lesions occur in patients with CSF profile positive for intrathecal IgM, IgG synthesis and higher number oligoclonal bands, a low number of transitional B cells at baseline, a low number of CD56bright NK cells, high levels of activating sICPs and low levels of inhibitory sICPs at baseline, and/or a presenting syndrome of optic neuritis or myelitis.
To investigate the research questions, MS patients will be enrolled from five Dutch MS centres in an observational study with a follow-up of 27 months. Patients will be asked to participate when they are being screened for DMT initiation and given 7 days to consider. Informed consent will be obtained by a doctor, part of the research team. Next to routine regular follow-up with brain MRI and outpatient clinic visits, patients will receive spinal cord MRI and a structured registration of clinical parameters and collection of blood samples. Towards the end of follow-up, it will be evaluated whether starting an extension study is of additional value.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Population of treatment-naïve relapsing-remitting MS patients, early in the disease course (within 5 years of first clinical event) between 18 - 65 years old, where a first DMT is initiated.
Key inclusion criteria (3 listed)
- Patients between 18 and 65 years old
- Patients diagnosed with relapsing-remitting MS (≤5 years of first clinical event)
- Treatment-naïve patients starting (currently in the Netherlands approved) DMT
Key exclusion criteria (9 listed)
- Patients who presented first clinical event more than five years ago
- Patients who have already started DMT
- Patients who are incapable of giving informed consent
- Patients who are unable to undergo local MRI scan, due to for instance
- Physical problems, for instance due to size/obesity (not fitting in regular MRI scanner), not being able to lie flat for extended periods of time (e.g. due to pain, shortness of breath)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Spinal cord lesion count
Time frame: 27 months
7 secondary outcomes
Brain MRI acitivity
Time frame: 27 months
Expanded disability status scale (EDSS)
Time frame: 27 months
Timed 25 foot walk test
Time frame: 27 months
Nine hole peg test
Time frame: 27 months
No evidence of disease activity
Time frame: 27 months
Biomarkers neuronal damage
Time frame: 27 months
Lower urinary tract symptoms
Time frame: 27 months
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 14 Feb 2025.
- Background: PubMed 34820734Di Sabatino E, Gaetani L, Sperandei S, Fiacca A, Guercini G, Parnetti L, Di Filippo M. The no evidence of disease activity (NEDA) concept in MS: impact of spinal cord MRI. J Neurol. 2022 Jun;269(6):3129-3135. doi: 10.1007/s00415-021-10901-2. Epub 2021 Nov 24.
- Background: PubMed 37683557Kreiter D, Spee R, Merry A, Hupperts R, Gerlach O. Effect of disease-modifying treatment on spinal cord lesion formation in multiple sclerosis: A retrospective observational study. Mult Scler Relat Disord. 2023 Nov;79:104994. doi: 10.1016/j.msard.2023.104994. Epub 2023 Sep 4.
- Background: PubMed 27481210Brownlee WJ, Altmann DR, Alves Da Mota P, Swanton JK, Miszkiel KA, Wheeler-Kingshott CG, Ciccarelli O, Miller DH. Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome. Mult Scler. 2017 Apr;23(5):665-674. doi: 10.1177/1352458516663034. Epub 2016 Aug 6.
- Background: PubMed 31494713Granella F, Tsantes E, Graziuso S, Bazzurri V, Crisi G, Curti E. Spinal cord lesions are frequently asymptomatic in relapsing-remitting multiple sclerosis: a retrospective MRI survey. J Neurol. 2019 Dec;266(12):3031-3037. doi: 10.1007/s00415-019-09526-3. Epub 2019 Sep 7.
- Background: PubMed 26459149Zecca C, Disanto G, Sormani MP, Riccitelli GC, Cianfoni A, Del Grande F, Pravata E, Gobbi C. Relevance of asymptomatic spinal MRI lesions in patients with multiple sclerosis. Mult Scler. 2016 May;22(6):782-91. doi: 10.1177/1352458515599246. Epub 2015 Oct 12.
- Derived from this study: PubMed 41998718Bouweriks D, Kreiter D, Knippenberg SAM, Damoiseaux JGMC, Smolders J, van Eijk JJJ, Mommers EHH, de Beukelaar JWK, Olde Dubbelink TBG, Merry AHH, Hupperts RMM, Gerlach OHH. MSpine: a prospective longitudinal study of spinal cord lesions in multiple sclerosis: MRI monitoring and prognostic factors for active disease. A study protocol. Neurol Res Pract. 2026 Apr 17;8(1):23. doi: 10.1186/s42466-026-00465-9.
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Zuyderland Medisch Centrum at 5 sites in Netherlands.
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 3 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. 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 Demmie Bouweriks, MD (+31884597603, d.bouweriks@zuyderland.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spinal cord lesion count (time frame: 27 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06827834, which also lists 6 linked publications.
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 14 Feb 2025.