Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: MRI, Neurocognitive examination for healthy subjects, blood sampling.
- Who it may be relevant to
- Registry conditions: Multiple Sclerosis (MS), Relapsing-remitting Multiple Sclerosis (RRMS), Secondary-progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS). Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Switzerland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
INsIDER: Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis
Overview
This project is to: 1. Quantify differences in axonal integrity and organization in aMS versus naPMS patients. 2. Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period. 3. Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.
Detailed description
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by multifocal inflammatory infiltrates, microglial activation and degradation of oligodendrocytes, myelin and axons. Clinical MS categories exhibit variable amount of central nervous system (CNS) damage and repair, depending on numerous variables including genetic, immunological, pathological and environmental factors.
Therefore, understanding the interplay between axonal damage (i.e. axonal demyelination/degeneration/loss/disorganization) and (ii) axonal repair (i.e. axonal remyelination/reorganization) in living MS patients may be the key to understand disease progression, to establish accurate disease monitoring criteria and to predict disease response to future reparative therapies. New in-vivo methods are necessary to elucidate the interplay between axonal damage and repair in the brain of living patients with MS. Advanced MRI (aMRI) permits a multifaced quantification of the various components of the axons and their organization. Neurite Orientation Dispersion and Density Imaging (NODDI) and Diffusion Kurtosis (DK) are new approaches in clinical research This study is to identify in vivo the specific neuropathological pattern of axonal damage and repair exhibited by active MS (aMS) and non-active progressive MS (naPMS) patient by leveraging the information provided by model-based diffusion metrics (NODDI, DK), Magnetization Transfer Imaging (MTI), Multi-echo Susceptibility-Based imaging (SBI), Myelin Water Imaging (MWI) and quantitative T1 relaxometry (qT1). These advanced MRI contrasts provide complementary and partially redundant information about the axonal structure and its organization (i.e. density and orientation of axons and dendrites in the brain tissue, axonal integrity and myelination, presence of myelin and iron, and brain tissue architecture). Therefore, their combination may prove high sensitivity and specificity to axonal damage and repair.
This project has 3 main aims:
Aim 1. Quantify differences in axonal integrity and organization in aMS versus naPMS patients.
Aim 2. Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.
Aim 3. Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.
Interventions
- Diagnostic test MRI
Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up. - Other Neurocognitive examination for healthy subjects
Neurocognitive examination for healthy subjects will be performed at both baseline and follow-up - Other blood sampling
Each enrolled subject will undergo a blood sampling (10 ml) at baseline
Primary outcome measures
- MRI- change in axonal integrity and organization over 2 years in aMS, naPMS and HC, by using machine learning techniques [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
Secondary outcome measures (5)
- Change in MUSIC Test [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
- Change in auditory verbal learning and memory test/ Verbaler Lern- und Merkfähigkeitstest (VLMT) [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
- Change in Symbol Digital Modalities Test (SDMT) [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
- Change in Brief Visuospatial Memory Test (BVMT) [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
- Change in Hospital Anxiety and Depression Scale (HADS) [Time frame: at baseline and 2 years (+/- 3 months) after baseline]
Eligibility criteria
Inclusion Criteria for patients:
- Patients may be diagnosed with:
- active RRMS (n=100): Relapsing-remitting course and > 1 clinical relapse and/or signs of MRI activity (> 1 Gd enhancing lesion) during the last year before study enrollment.
- non-active PMS (n=100): Progressive course (PPMS or SPMS) and no clinical relapses and/or signs of MRI activity during the last year before study enrollment.
- Age 18-80 years old
- No other neurological or psychiatric disorder
Inclusion criteria for healthy controls:
- Age 18-80 years old
- No other neurological or psychiatric disorder
Exclusion Criteria for patients and healthy controls:
- Pregnancy
- Contraindication to MRI (eg, claustrophobia, metallic implants, pacemaker etc).
- Inability to give consent
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Switzerland · 1 center
- University Hospital Basel, Department of Neurology — Basel
Identifiers
NCT: NCT05177523 · 2018-01174; me18Granziera