Multiple Sclerosis (MS)INsIDERNCT05177523
Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis
An observational study of Multiple Sclerosis (MS) and Relapsing-remitting Multiple Sclerosis (RRMS), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis (MS), Relapsing-remitting Multiple Sclerosis (RRMS), Secondary-progressive Multiple Sclerosis (SPMS)
- What is being tested?
- MRI, Neurocognitive examination for healthy subjects and blood sampling
- How many people
- 300 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 Sep 2018to Dec 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The recruitment of MS patients will take place at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel). Healthy subjects will be recruited by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board.
Who may be able to join
- 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
- Age 18-80 years old
- No other neurological or psychiatric disorder
Who cannot join
- Pregnancy
- Contraindication to MRI (eg, claustrophobia, metallic implants, pacemaker etc).
- Inability to give consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital Basel, Department of Neurology
Basel, 4031
Cristina Granziera, Prof. Dr. med., cristina.granziera@usb.ch
Cristina Granziera, Prof. Dr. med.
About this study
Official title: INsIDER: Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis
This project is to:
- Quantify differences in axonal integrity and organization in aMS versus naPMS patients.
- Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.
- Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.
Read the 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.
- Conditions
- Multiple Sclerosis (MS), Relapsing-remitting Multiple Sclerosis (RRMS), Secondary-progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS)
- Being tested
- MRI, Neurocognitive examination for healthy subjects, blood sampling
- Keywords
- axonal damage, axonal demyelination, axonal degeneration, axonal loss, axonal disorganization, axonal repair, axonal remyelination, axonal reorganization, Advanced MRI (aMRI), Neurite Orientation Dispersion and Density Imaging (NODDI), Diffusion Kurtosis (DK), Magnetization Transfer Imaging (MTI), Multi-echo Susceptibility-Based imaging (SBI), Myelin Water Imaging (MWI), T1 relaxometry (quantitative T1, qT1), machine learning technique
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up.
Neurocognitive examination for healthy subjectsOther
Neurocognitive examination for healthy subjects will be performed at both baseline and follow-up
blood samplingOther
Each enrolled subject will undergo a blood sampling (10 ml) at baseline
| Study group | Role | What they receive |
|---|---|---|
| MS patient group | Recruitment of 200 MS patients at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel) Receives: Diagnostic Test: MRI; Other: blood sampling | |
| control group (HC) | Recruitment of 100 healthy controls (HC) by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board. Receives: Diagnostic Test: MRI; Other: Neurocognitive examination for healthy subjects; Other: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI- change in axonal integrity and organization over 2 years in aMS, naPMS and HC, by using machine learning techniques
After magnetic resonance (MR) data preprocessing (image denoising, standardization, bias field correction) classical machine learning techniques will be used to classify a number of MRI metrics which will be averaged over a number of regions of interest (ROIs) including (i) normal-appearing white and brain matter in brain lobes and cervical spinal cord, (ii) basal ganglia, (iii) thalamus, (vi) cerebellum, MS lesions. Complex input data (voxels/patches) will be generated to learn from, then a deep learning model for supervised classification will be defined to identify the combination of aMRI parameters that characterize aMS, naPMS and HC.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Secondary outcomes (5)
Change in MUSIC Test
Neurocognitive examination. MUSIC is a rapid (about 10-12 min) multiple domain cognitive screening test reflecting the most frequently impaired cognitive domains in MS. At 20-30 points the performance is in the normal range, at 16-19 points there is at most slight cognitive dysfunction, at 11-15 points there is moderate cognitive dysfunction and at <= 10 points there is a clear cognitive dysfunction.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Change in auditory verbal learning and memory test/ Verbaler Lern- und Merkfähigkeitstest (VLMT)
Questionnaire to investigate memory performance, learning and recall information. Five presentations of a 15-word list are given, each followed by attempted recall. This is followed by a second 15-word interference list (list B), followed by recall of list A. Delayed recall and recognition are also tested.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Change in Symbol Digital Modalities Test (SDMT)
The SDMT detects cognitive impairment by measuring the time to pair abstracts. Using a reference key, the test taker has 90 seconds to pair specific numbers with given geometric figures.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Change in Brief Visuospatial Memory Test (BVMT)
The BVMT measures visuospatial memory In three Learning Trials, the respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Last, a Recognition Trial, in which the respondent is asked to identify which of 12 figures were included among the original geometric figures, is administered. Slower processing speed is associated with poorer learning and memory performance.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Change in Hospital Anxiety and Depression Scale (HADS)
HADS is a fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression.
Measured: at baseline and 2 years (+/- 3 months) after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study start4 Sep 2018
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis (MS)Studies 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
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Sponsor
- Investigators
- Cristina Granziera, Prof. Dr. med., Principal investigator, Department of Neurology, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05177523
- Sponsor's protocol ID
- 2018-01174; me18Granziera
- Other IDs
- 2018
- Acronym
- INsIDER
- Status last verified
- Dec 2024
- First submitted
- 15 Dec 2021
- Last updated
- 16 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INsIDER: Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05177523
- Acronym / sponsor ID
- INsIDER / 2018-01174; me18Granziera
- Conditions
- Multiple Sclerosis (MS), Relapsing-remitting Multiple Sclerosis (RRMS), Secondary-progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS)
- Keywords
- axonal damage, axonal demyelination, axonal degeneration, axonal loss, axonal disorganization, axonal repair, axonal remyelination, axonal reorganization
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- 4 Sep 2018 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 4 Jan 2022 (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.
This project is to:
- Quantify differences in axonal integrity and organization in aMS versus naPMS patients.
- Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MS patient group | – | Diagnostic Test: MRI, Other: blood samplingRecruitment of 200 MS patients at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel) |
| control group (HC) | – | Diagnostic Test: MRI, Other: Neurocognitive examination for healthy subjects, Other: blood samplingRecruitment of 100 healthy controls (HC) by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The recruitment of MS patients will take place at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel). Healthy subjects will be recruited by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board.
Key inclusion criteria (7 listed)
- Patients may be diagnosed with:
- Age 18-80 years old
- No other neurological or psychiatric disorder
- Age 18-80 years old
- No other neurological or psychiatric disorder
Key exclusion criteria (3 listed)
- Pregnancy
- Contraindication to MRI (eg, claustrophobia, metallic implants, pacemaker etc).
- Inability to give consent
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 |
|---|---|---|
| MRIEach enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up. | Diagnostic test | MS patient group, control group (HC) |
| Neurocognitive examination for healthy subjectsNeurocognitive examination for healthy subjects will be performed at both baseline and follow-up | Other | control group (HC) |
| blood samplingEach enrolled subject will undergo a blood sampling (10 ml) at baseline | Other | MS patient group, control group (HC) |
Primary outcome
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
After magnetic resonance (MR) data preprocessing (image denoising, standardization, bias field correction) classical machine learning techniques will be used to classify a number of MRI metrics which will be averaged over a number of regions of interest (ROIs) including (i) normal-appearing white and brain matter in brain lobes and cervical spinal cord, (ii) basal ganglia, (iii) thalamus, (vi) cerebellum, MS lesions. Complex input data (voxels/patches) will be generated to learn from, then a deep learning model for supervised classification will be defined to identify the combination of aMRI parameters that characterize aMS, naPMS and HC.
5 secondary outcomes
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
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 16 Dec 2024.
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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.
Cristina Granziera, Prof. Dr. med. principal investigator
Department of Neurology, University Hospital Basel
1 site 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 (MS) and Relapsing-remitting Multiple Sclerosis (RRMS), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 3 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 16 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. 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 Cristina Granziera, Prof. Dr. med. (+41 61-32 85 665, cristina.granziera@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 16 Dec 2024; AzTrials last refreshed its copy on 29 Oct 2026.