search
Back to results

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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Clinical assessment
Neuropsychological evaluation
Psychological evaluation
MRI Evaluation
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Multiple Sclerosis focused on measuring Clinically Isolated Syndrome, NODDI, Hippocampus, episodic memory function, dentate gyrus, MRI

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • CHU de Bordeaux - service de neurologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CIS patients

Control

Arm Description

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

50 Healthy controls

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

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).
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).
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).
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).
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.
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.
Inflammatory activity
The inflammatory activity will be the number of T1-gadolinium enhancing lesions in whole brain and in the hippocampus, thalamus and cerebellum.
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.
Verbal episodic memory test
California Verbal Learning Test-Second version (CVLT-II)
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)
Information processing speed and attention score
Computerized Speed Cognitive Test (CSCT) and TAP
Working memory score
Paced-Auditory-Serial-Addition-Test (PASAT) and span

Full Information

First Posted
August 7, 2018
Last Updated
March 7, 2023
Sponsor
University Hospital, Bordeaux
search

1. Study Identification

Unique Protocol Identification Number
NCT03692975
Brief Title
MRI Hippocampal Microstructure and Episodic Memory in Early Multiple Sclerosis
Acronym
Micro-MS
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
February 12, 2019 (Actual)
Primary Completion Date
February 24, 2023 (Actual)
Study Completion Date
February 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Clinically Isolated Syndrome, NODDI, Hippocampus, episodic memory function, dentate gyrus, MRI

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CIS patients
Arm Type
Experimental
Arm Description
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
Arm Title
Control
Arm Type
Active Comparator
Arm Description
50 Healthy controls
Intervention Type
Other
Intervention Name(s)
Clinical assessment
Intervention Description
Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded.
Intervention Type
Other
Intervention Name(s)
Neuropsychological evaluation
Intervention Description
cognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory.
Intervention Type
Other
Intervention Name(s)
Psychological evaluation
Intervention Description
included questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve
Intervention Type
Device
Intervention Name(s)
MRI Evaluation
Intervention Description
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 Measure Information:
Title
Index of orientation-dispersion (IOD)
Description
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).
Time Frame
At baseline (day 0)
Title
Index of Neurite density (ND)
Description
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).
Time Frame
At baseline (day 0)
Secondary Outcome Measure Information:
Title
Diffusion parameters : Index of orientation-dispersion
Description
This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Time Frame
At baseline (day 0)
Title
Diffusion parameters : Neurite density
Description
This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Time Frame
At baseline (day 0)
Title
Diffusion parameters : Fractional Anisotropy
Description
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).
Time Frame
At baseline (day 0)
Title
Diffusion parameters : Mean diffusivity
Description
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).
Time Frame
At baseline (day 0)
Title
Atrophy parameters
Description
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.
Time Frame
At baseline (day 0)
Title
Lesion volume
Description
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.
Time Frame
At baseline (day 0)
Title
Inflammatory activity
Description
The inflammatory activity will be the number of T1-gadolinium enhancing lesions in whole brain and in the hippocampus, thalamus and cerebellum.
Time Frame
At baseline (day 0)
Title
Connectivity
Description
The seed-based connectivity is measured between hippocampus and others cerebral regions (Thalamus, cerebellum…) from Diffusion Tensor Imaging (DTI) and resting state functional imaging.
Time Frame
At baseline (day 0)
Title
Verbal episodic memory test
Description
California Verbal Learning Test-Second version (CVLT-II)
Time Frame
At baseline (day 0)
Title
Visual episodic memory score
Description
Brief Visual Memory Test-Revised (BVMT-R) and Memonic Similarity Task (MST) : visuospatial memory tests (2 scores pour BVMT-R, 3 scores pour MST)
Time Frame
At baseline (day 0)
Title
Information processing speed and attention score
Description
Computerized Speed Cognitive Test (CSCT) and TAP
Time Frame
At baseline (day 0)
Title
Working memory score
Description
Paced-Auditory-Serial-Addition-Test (PASAT) and span
Time Frame
At baseline (day 0)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aurélie RUET, MD, PhD
Organizational Affiliation
CHU Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eric FRISON, MD, PhD
Organizational Affiliation
CHU Bordeaux
Official's Role
Study Chair
Facility Information:
Facility Name
CHU de Bordeaux - service de neurologie
City
Bordeaux
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

MRI Hippocampal Microstructure and Episodic Memory in Early Multiple Sclerosis

We'll reach out to this number within 24 hrs