DTI in Children With Multiple Sclerosis

Study Overview
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Brief Summary
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This is a prospective, non-randomised, non-blinded, single center study of children and adolescents with multiple sclerosis and clinically isolated syndrome to detect differences or early changes in diffusion-weighted imaging (DTI) by magnetic resonance imaging (MRI).

Detailed Description
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In children and adolescents with either multiple sclerosis or clinically isolated syndrome an MRI with special DTI-sequences of the brain is performed at timepoint of first manifestation of disease and every 6 months at 3 Tesla MRI according to a specific investigation protocol. Besides MRI-DTI several clinical data are recorded every 6 months: expanded disability status scale (EDSS) disease activity/ relapse rate lesion load (number of T2-lesions) brain atrophy visual and somatosensoric evoked potentials (VEP, SSEP) neuropsychological examination Furthermore a complete neurological examination is done every 6 months and particular medication of each patient is recorded in a specific investigator form (case report form, CRF)

Official Title
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Monitoring of Neurodegenerative Processes in Children With Multiple Sclerosis by Diffusion-weighed Magnetic Resonance Imaging (DTI)

Conditions
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Multiple Sclerosis - Relapsing Remitting, Clinically Isolated Syndrome, CNS Demyelinating

Intervention / Treatment
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* Other: DTI-MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent diagnosis of multiple sclerosis (MS) according to the McDonald criteria 2010 and the consensus recommendations of International Pediatric MS Study Group (IPMSSG) (Krupp et al 2013) diagnosis of CIS according to the consensus recommendation of IPMSSG (Krupp et al 2013) all types of medication/therapy Exclusion Criteria: pregnancy claustrophobia allergic reaction of gadolinium (contrast medium) implantation of cardiac device implantation of neurostimulators implantation of cochlea implants presence of tattooing (over 20% of body surface) presence of permanent-make-up presence of permanent transdermal patches presence of special catheter systems with temperature probes which cannot be removed implantation of metalliferous implants or implants which could contain metal traces implantation of artificial heart valves implantation of stents or coils presence of metal fragments in the eyes

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: DTI-MRI<br>MRI of the brain with specific DTI-sequences according to a specific investigation protocol | Other: DTI-MRI<br>* MRI of the brain with special DTI-sequences are performed in each child with multiple sclerosis or clinically isolated syndrome at timepoint of first manifestation and every 6 months in a longterm follow-up of 3 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline fractional anisotropy (FA) at 36 months measured by cerebral MRI and special DTI sequences | measured by cerebral MRI and special DTI sequences | every 6 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| change from baseline apparent diffusion coefficient (ADC) at 36 months measured by cerebral MRI and special DTI sequences | measured by cerebral MRI and special DTI sequences | every 6 months (from date of randomization until the end of the study, assessed up to 36 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease activity (relapse rate, lesion load) | relapse rate, lesion load | every 6 months (from date of randomization until the end of the study after 36 months) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | every 6 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| EDSS (Expanded disability status scale, Values between 0-10) | Expanded disability status scale, Values between 0-10 | every six months (from date of randomization until the end of the study, assessed up to 36 months) | 
| spinal lesion load measured by spinal MRI (which is performed in each participant every 12 months) | measured by spinal MRI (which is performed in each participant every 12 months) | every 12 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| VEP-Score | score of visual evoked potential (amplitudes, latency) Values between 0-4 | every 6 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| SSEP somatosensory evoked potentials, records of amplitudes and latency | somatosensory evoked potentials, records of amplitudes and latency | every 12 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| Medication particular medication of each patient | particular medication of each patient | every 6 months (from date of randomization until the end of the study, assessed up to 36 months) | 
| neurocognitive deficits neuropsychological test battery | neuropsychological test battery including the following tests Standard Progressive Matrices (SPM) VLMT - verbal comprehension and retentivity test by Helmstaedter ROF - Rey-Osterrieth-Figure TMT A/B - Trail-Making-Test Form A and B RWT - Regensburg word fluency test block-span Corsi count span test SDMT - Symbol Digit Modalities Test BDI-II, Revision - Beck Depressions-Inventory PedsQL - Pediatric Quality of Life Inventory | every 12 months (from date of randomization until the end of the study, assessed up to 36 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric multiple sclerosis, clinically isolated syndrome in children, biomarker, magnetic resonance imaging, diffusion weighted imaging