Multiple SclerosisMicro-MSNCT03692975
MRI Hippocampal Microstructure and Episodic Memory in Early Multiple Sclerosis
A study testing Clinical assessment, Neuropsychological evaluation and Psychological evaluation in people with Multiple Sclerosis, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
Clinically isolated syndrome (CIS) can evolve into multiple sclerosis. In CIS patients, episodic memory is frequently impaired. Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Clinical assessment, Neuropsychological evaluation and Psychological evaluation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteFrance
- Study dates
- 12 Feb 2019to 24 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- - PATIENTS:
- Men and Women,
- Age 18-60 years,
- Native French language,
- Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially beginning multiple sclerosis (MS) whatever the mode of presentation,
- Between 60 and 180 days from the onset,
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- At least two clinically silent lesions on their T2-weighted brain or spinal MRI scan with a size of least 3 mm, at least one of which being cerebral, ovoid, or periventricular,
- Willing to participate and to sign informed consent.
- - HEALTHY CONTROLS
- Men and Women,
- Age 18-60years,
- Native French language,
- Willing to participate and to sign informed consent.
Who cannot join
- - PATIENTS:
- Prior documented neurological episode suggestive of MS,
- History of neurological disease and/or other neurological diseases,
- Psychiatric diseases,
- Known chronic systemic diseases as judged by the investigator,
- Alcohol or other addiction to toxic,
Show all 27Show fewer
- Disabling visual or motor problems preventing participation to neuropsychological assessments,
- Acquisition disorders : Dyslexia, Dysphasia, Dyscalculia and dyspraxia,
- Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 30 days,
- Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia),
- Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily,
- Illiteracy, is unable to count or to read,
- Pregnant or breastfeeding women,
- Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
- - HEALTHY CONTROLS
- History of neurological disease and/or neurological diseases,
- Psychiatric diseases,
- Known chronic systemic diseases as judged by the investigator,
- Alcohol or other addiction to toxic,
- Acquisition disorders: Dyslexia, Dysphasia, Dyscalculia and dyspraxia,
- Known cognitive impairment or Prior neuropsychological testing with the same tests less than one year,
- Hypnotic or anxiolytic or antidepressive treatment,
- Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily,
- Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia) or refusing MRI,
- Illiteracy, unable to count or to read,
- Pregnant or breastfeeding women,
- Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hippocampal Microstructure Assessed by a New MRI Sequence and Episodic Memory at the Early Stage of Multiple Sclerosis: Comparison Between Patients After a Clinically Isolated Syndrome (CIS) and Controls
Clinically isolated syndrome (CIS) can evolve into multiple sclerosis. In CIS patients, episodic memory is frequently impaired. Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in the white matter (WM) and dendrites in the grey matter (GM). The aim of this study is to evaluate microstructural abnormalities in the dentate gyrus of the hippocampus in CIS patients compared to controls.
Read the detailed description
Cognitive deficiencies could occur after a first clinical event of the central nervous system suggestive of MS called clinically isolated syndrome (CIS). Cognitive impairment concerned several cognitive domains including episodic memory, attention, working memory and executive functions. It is recognized the negative impact of cognitive impairment on quality of life and vocational status in patients living with MS. Slowness of information processing speed is the main cognitive dysfunction observed in MS seen at the earliest stage of the disease. Recently an international group of MS experts has explain IPS and episodic memory as the minimal cognitive assessment in patients with MS. Visuospatial and verbal episodic memory deficits have been observed in 18 to 28% of patients assessed after a CIS.
Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in white matter and dendrite in the gray matter. No study has used the NODDI in CIS patients and very few studies have been conducted in MS.
The hypothesis is that the dentate gyrus is the anatomical substrate of early episodic memory dysfunction in patients included after a CIS.
The identification of predictive MRI biomarker of memory impairment would be a useful and clinically relevant prognostic marker at the early stage of MS. This biomarker could contribute to determine the prognosis of the disease and could help for the monitoring of the patients in clinical practice and clinical trials.
- Conditions
- Multiple Sclerosis
- Being tested
- Clinical assessment, Neuropsychological evaluation, Psychological evaluation, MRI Evaluation
- Keywords
- Clinically Isolated Syndrome, NODDI, Hippocampus, episodic memory function, dentate gyrus, MRI
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical assessmentOther
Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded.
Neuropsychological evaluationOther
cognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory.
Psychological evaluationOther
included questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve
MRI EvaluationDevice
Diffusion including NODDI, 3DT1 with and without gadolinium, 3D-FLAIR before and after gadolinium infusion, 3D White Matter nulled-MPRAGE, 3D Double-Inversion recovery sequences-weighted imaging and Resting state functional MRI
| Study group | Role | What they receive |
|---|---|---|
| CIS patients | Experimental | Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation Receives: Other: Clinical assessment; Other: Neuropsychological evaluation; Other: Psychological evaluation; Device: MRI Evaluation |
| Control | Active comparator | 50 Healthy controls Receives: Other: Neuropsychological evaluation; Other: Psychological evaluation; Device: MRI Evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Index of orientation-dispersion (IOD)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Index of Neurite density (ND)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Secondary outcomes (12)
Diffusion parameters : Index of orientation-dispersion
This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Diffusion parameters : Neurite density
This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Diffusion parameters : Fractional Anisotropy
This parameter is measured in dentate gyrus of hippocampus, thalamus and cerebellum from diffusion imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Diffusion parameters : Mean diffusivity
This parameter is measured in dentate gyrus of hippocampus, thalamus and cerebellum from diffusion imaging blind to the nature of the patient's group (CIS patients and controls).
Measured: At baseline (day 0)
Atrophy parameters
Normalized total brain volume and normalized total WM and total GM volumes and in hippocampus, thalamus and cerebellum from 3D-T1, 3D-DIR, 3D-WMn-MPRAGE in CIS patients and controls in double-blind.
Measured: At baseline (day 0)
Lesion volume
Normalized volume of lesions double-blind measured by a semi-automatic method based on 3 D Fast Fluid-attenuated inversion-recuperation (3D-FLAIR) and 3 D Double Inversion Recovery (3D-DIR) in whole brain and in the hippocampus, thalamus and cerebellum.
Measured: At baseline (day 0)
Inflammatory activity
The inflammatory activity will be the number of T1-gadolinium enhancing lesions in whole brain and in the hippocampus, thalamus and cerebellum.
Measured: At baseline (day 0)
Connectivity
The seed-based connectivity is measured between hippocampus and others cerebral regions (Thalamus, cerebellum…) from Diffusion Tensor Imaging (DTI) and resting state functional imaging.
Measured: At baseline (day 0)
Verbal episodic memory test
California Verbal Learning Test-Second version (CVLT-II)
Measured: At baseline (day 0)
Visual episodic memory score
Brief Visual Memory Test-Revised (BVMT-R) and Memonic Similarity Task (MST) : visuospatial memory tests (2 scores pour BVMT-R, 3 scores pour MST)
Measured: At baseline (day 0)
Information processing speed and attention score
Computerized Speed Cognitive Test (CSCT) and TAP
Measured: At baseline (day 0)
Working memory score
Paced-Auditory-Serial-Addition-Test (PASAT) and span
Measured: At baseline (day 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2018
- Study start12 Feb 2019
- Primary completion24 Feb 2023
- Study completion24 Feb 2023
Why it stopped: target number of patient not reached
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aurélie RUET, MD, PhD, Principal investigator, University Hospital, BordeauxEric FRISON, MD, PhD, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03692975
- Sponsor's protocol ID
- CHUBX 2017/30
- Acronym
- Micro-MS
- Status last verified
- Mar 2023
- First submitted
- 7 Aug 2018
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fournet A, Munsch F, Koubiyr I, Vidal JP, Morell-Ortega S, Saubusse A, Charre-Morin J, Lataste KK, Lavielle A, Bei Z, Coupe P, Barbeau EJ, Kumar VJ, Hornberger M, Dousset V, Brochet B, Manjon JV, Ruet A, Tourdias T. Interthalamic adhesion alterations in multiple sclerosis: associations with thalamic damage and cognition. J Neurol. 2026 Aug 20;273(9):535. doi: 10.1007/s00415-026-14069-5.
PubMed 42624921
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hippocampal Microstructure Assessed by a New MRI Sequence and Episodic Memory at the Early Stage of Multiple Sclerosis: Comparison Between Patients After a Clinically Isolated Syndrome (CIS) and Controls
- ClinicalTrials.gov ID
- NCT03692975
- Acronym / sponsor ID
- Micro-MS / CHUBX 2017/30
- Conditions
- Multiple Sclerosis
- Keywords
- Clinically Isolated Syndrome, NODDI, Hippocampus, episodic memory function, dentate gyrus, MRI
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: target number of patient not reached
- Enrolment
- 84 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 12 Feb 2019 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 24 Feb 2023 (actual)
- First posted
- 2 Oct 2018 (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.
Clinically isolated syndrome (CIS) can evolve into multiple sclerosis. In CIS patients, episodic memory is frequently impaired. Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in the white matter (WM) and dendrites in the grey matter (GM). The aim of this study is to evaluate microstructural abnormalities in the dentate gyrus of the hippocampus in CIS patients compared to controls.
Detailed description
Cognitive deficiencies could occur after a first clinical event of the central nervous system suggestive of MS called clinically isolated syndrome (CIS). Cognitive impairment concerned several cognitive domains including episodic memory, attention, working memory and executive functions. It is recognized the negative impact of cognitive impairment on quality of life and vocational status in patients living with MS. Slowness of information processing speed is the main cognitive dysfunction observed in MS seen at the earliest stage of the disease. Recently an international group of MS experts has explain IPS and episodic memory as the minimal cognitive assessment in patients with MS. Visuospatial and verbal episodic memory deficits have been observed in 18 to 28% of patients assessed after a CIS.
Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in white matter and dendrite in the gray matter. No study has used the NODDI in CIS patients and very few studies have been conducted in MS.
The hypothesis is that the dentate gyrus is the anatomical substrate of early episodic memory dysfunction in patients included after a CIS.
The identification of predictive MRI biomarker of memory impairment would be a useful and clinically relevant prognostic marker at the early stage of MS. This biomarker could contribute to determine the prognosis of the disease and could help for the monitoring of the patients in clinical practice and clinical trials.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CIS patients | Experimental | Other: Clinical assessment, Other: Neuropsychological evaluation, Other: Psychological evaluation, Device: MRI EvaluationClinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation |
| Control | Active comparator | Other: Neuropsychological evaluation, Other: Psychological evaluation, Device: MRI Evaluation50 Healthy controls |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- - PATIENTS:
- - HEALTHY CONTROLS
Key exclusion criteria (27 listed)
- - PATIENTS:
- - HEALTHY CONTROLS
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 |
|---|---|---|
| Clinical assessmentExpanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded. | Other | CIS patients |
| Neuropsychological evaluationcognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory. | Other | CIS patients, Control |
| Psychological evaluationincluded questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve | Other | CIS patients, Control |
| MRI EvaluationDiffusion including NODDI, 3DT1 with and without gadolinium, 3D-FLAIR before and after gadolinium infusion, 3D White Matter nulled-MPRAGE, 3D Double-Inversion recovery sequences-weighted imaging and Resting state functional MRI | Device | CIS patients, Control |
Primary outcome
Index of orientation-dispersion (IOD)
Time frame: At baseline (day 0)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Index of Neurite density (ND)
Time frame: At baseline (day 0)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
12 secondary outcomes
Diffusion parameters : Index of orientation-dispersion
Time frame: At baseline (day 0)
Diffusion parameters : Neurite density
Time frame: At baseline (day 0)
Diffusion parameters : Fractional Anisotropy
Time frame: At baseline (day 0)
Diffusion parameters : Mean diffusivity
Time frame: At baseline (day 0)
Atrophy parameters
Time frame: At baseline (day 0)
Lesion volume
Time frame: At baseline (day 0)
Inflammatory activity
Time frame: At baseline (day 0)
Connectivity
Time frame: At baseline (day 0)
Verbal episodic memory test
Time frame: At baseline (day 0)
Visual episodic memory score
Time frame: At baseline (day 0)
Information processing speed and attention score
Time frame: At baseline (day 0)
Working memory score
Time frame: At baseline (day 0)
Results and safety
The study was stopped early (reason given: target number of patient not reached). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Derived from this study: PubMed 42624921Fournet A, Munsch F, Koubiyr I, Vidal JP, Morell-Ortega S, Saubusse A, Charre-Morin J, Lataste KK, Lavielle A, Bei Z, Coupe P, Barbeau EJ, Kumar VJ, Hornberger M, Dousset V, Brochet B, Manjon JV, Ruet A, Tourdias T. Interthalamic adhesion alterations in multiple sclerosis: associations with thalamic damage and cognition. J Neurol. 2026 Aug 20;273(9):535. doi: 10.1007/s00415-026-14069-5.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Aurélie RUET, MD, PhD principal investigator
University Hospital, Bordeaux
Eric FRISON, MD, PhD study chair
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical assessment, Neuropsychological evaluation and Psychological evaluation in people with Multiple Sclerosis, run by University Hospital, Bordeaux at 1 site in France.
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 13 inclusion and 27 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: stopped early, as of the sponsor's last update on 26 Jun 2026. 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 France. 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?
The study was stopped early (reason given: target number of patient not reached). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Index of orientation-dispersion (IOD) (time frame: At baseline (day 0)). The study lists 2 primary outcomes in all. 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 NCT03692975, which also lists 1 linked publication.
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 26 Jun 2026.