Spinal Cord Monitoring in Multiple Sclerosis (MSpine)

February 10, 2025 updated by: Zuyderland Medisch Centrum

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.

Study Overview

Status

Recruiting

Conditions

Multiple Sclerosis

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.

2. 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 Type

Observational

Enrollment (Estimated)

155

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Demmie Bouweriks, MD
Phone Number: +31884597603
Email: d.bouweriks@zuyderland.nl

Study Locations

Netherlands
- Brabant
  - 's-Hertogenbosch, Brabant, Netherlands, 5223GZ
    - Not yet recruiting
    - Jeroen Bosch Ziekenhuis
    - Contact:
      
      Jeroen van Eijk
      
      Phone Number: +31735532325
      
      Email: j.eijkvan@jbz.nl
    - Contact:
      
      Jeroen van Eijk
- Gelderland
  - Arnhem, Gelderland, Netherlands, 6815AD
    - Not yet recruiting
    - Rijnstate
    - Contact:
      
      Tom Olde Dubbelink
      
      Phone Number: +31880058888
      
      Email: toldedubbelink@rijnstate.nl
    - Contact:
      
      Tom Olde Dubbelink
- Limburg
  - Geleen, Limburg, Netherlands, 6162BG
    - Recruiting
    - Zuyderland Medisch Centrum
    - Contact:
      
      Demmie Bouweriks, MD
      
      Phone Number: +31884597603
      
      Email: d.bouweriks@zuyderland.nl
    - Contact:
      
      Oliver Gerlach
- Zuid-Holland
  - Dordrecht, Zuid-Holland, Netherlands, 3318AT
    - Recruiting
    - Albert Schweitzer ziekenhuis
    - Contact:
      
      Janet de Beukelaar
      
      Phone Number: +31786541111
      
      Email: beukelaarj@asz.nl
    - Contact:
      
      Janet de Beukelaar
  - Rotterdam, Zuid-Holland, Netherlands, 3015GD
    - Not yet recruiting
    - Erasmus MC
    - Contact:
      
      Joost Smolders
      
      Phone Number: +31107040130
      
      Email: j.j.f.m.smolders@erasmusmc.nl
    - Contact:
      
      Joost Smolders

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Spinal cord lesion count Time Frame: 27 months	27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain MRI acitivity Time Frame: 27 months	Number of new (new T2, T1 gadolinium-enhancing) and expanding lesions	27 months
Expanded disability status scale (EDSS) Time Frame: 27 months	Measured at 3, 15 and 27 months	27 months
Timed 25 foot walk test Time Frame: 27 months	Measured at 3, 15 and 27 months	27 months
Nine hole peg test Time Frame: 27 months	Measured at 3, 15 and 27 months	27 months
No evidence of disease activity Time Frame: 27 months	Composite outcome: no relapses, no progression independent of relapse activity, no new lesions on brain or spinal cord MRI	27 months
Biomarkers neuronal damage Time Frame: 27 months	Neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAP)	27 months
Lower urinary tract symptoms Time Frame: 27 months	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)	27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zuyderland Medisch Centrum

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 6, 2024

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

February 10, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)