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MRI Hippocampal Microstructure and Episodic Memory in Early Multiple Sclerosis (Micro-MS)

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ClinicalTrials.gov Identifier: NCT03692975
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Other: Clinical assessment Other: Neuropsychological evaluation Other: Psychological evaluation Device: MRI Evaluation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : February 12, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CIS patients
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
Other: Clinical assessment
Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded.

Other: Neuropsychological evaluation
cognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory.

Other: Psychological evaluation
included questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve

Device: MRI Evaluation
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

Active Comparator: Control
50 Healthy controls
Other: Neuropsychological evaluation
cognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory.

Other: Psychological evaluation
included questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve

Device: MRI Evaluation
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




Primary Outcome Measures :
  1. 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).

  2. 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).


Secondary Outcome Measures :
  1. Diffusion parameters : Index of orientation-dispersion [ Time Frame: At baseline (day 0) ]
    This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).

  2. Diffusion parameters : Neurite density [ Time Frame: At baseline (day 0) ]
    This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).

  3. Diffusion parameters : Fractional Anisotropy [ Time Frame: At baseline (day 0) ]
    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).

  4. Diffusion parameters : Mean diffusivity [ Time Frame: At baseline (day 0) ]
    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).

  5. Atrophy parameters [ Time Frame: At baseline (day 0) ]
    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.

  6. Lesion volume [ Time Frame: At baseline (day 0) ]
    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.

  7. Inflammatory activity [ Time Frame: At baseline (day 0) ]
    The inflammatory activity will be the number of T1-gadolinium enhancing lesions in whole brain and in the hippocampus, thalamus and cerebellum.

  8. Connectivity [ Time Frame: At baseline (day 0) ]
    The seed-based connectivity is measured between hippocampus and others cerebral regions (Thalamus, cerebellum…) from Diffusion Tensor Imaging (DTI) and resting state functional imaging.

  9. Verbal episodic memory test [ Time Frame: At baseline (day 0) ]
    California Verbal Learning Test-Second version (CVLT-II)

  10. Visual episodic memory score [ Time Frame: At baseline (day 0) ]
    Brief Visual Memory Test-Revised (BVMT-R) and Memonic Similarity Task (MST) : visuospatial memory tests (2 scores pour BVMT-R, 3 scores pour MST)

  11. Information processing speed and attention score [ Time Frame: At baseline (day 0) ]
    Computerized Speed Cognitive Test (CSCT) and TAP

  12. Working memory score [ Time Frame: At baseline (day 0) ]
    Paced-Auditory-Serial-Addition-Test (PASAT) and span



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • - 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,
    • 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.

Exclusion Criteria:

  • - 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,
    • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03692975


Contacts
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Contact: Aurélie RUET, MD, PhD (0)5 56 79 55 21 ext +33 aurelie.ruet@chu-bordeaux.fr
Contact: Mathilde DELOIRE, PhD (0)5 57 82 12 75 ext +33 mathilde.deloire@chu-bordeaux.fr

Locations
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France
CHU de Bordeaux - service de neurologie Recruiting
Bordeaux, France
Contact: Aurélie RUET, MD, PhD    (0)5 56 79 55 21 ext +33    aurelie.ruet@chu-bordeaux.fr   
Contact: Mathilde DELOIRE, PhD    (0)5 57 82 12 75 ext +33    mathilde.deloire@chu-bordeaux.fr   
Principal Investigator: Aurélie RUET, MD, PhD         
Sub-Investigator: Bruno BROCHET, Prof         
Sub-Investigator: Jean-Christophe OUALLET, MD, PhD         
Sub-Investigator: Cécile DULAU, MD         
Sub-Investigator: Amandine MOROSO, MD         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
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Principal Investigator: Aurélie RUET, MD, PhD CHU - Bordeaux
Study Chair: Paul PEREZ, MD, PhD CHU - Bordeaux
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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03692975    
Other Study ID Numbers: CHUBX 2017/30
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
Clinically Isolated Syndrome
NODDI
Hippocampus
episodic memory function
dentate gyrus
MRI
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases