Prospective Longitudinal 1-year Study of the Correlation Between Cognitive Functioning in Patients With Clinically Isolated Syndrome Suggestive of Multiple Sclerosis and Disconnection in the Brain Assessed by MRI (SCI-COG)

Prospective Longitudinal 1-year Study of the Correlation Between Cognitive Functioning in Patients With Clinically Isolated Syndrome Suggestive of Multiple Sclerosis and Disconnection in the Brain Assessed by MRI:"SCI-COG" Study

Clinically isolated demyelinating syndromes (CIS) can evolve into multiple sclerosis (MS). Cognitive deficiencies could occur at this early stage and concern mainly information processing speed (IPS) and their mechanisms are not fully understood. Diffusion Tensor Imaging (DTI) can help in the understanding of these mechanisms.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Brain MRI; Clinically Isolated Demyelinating Syndromes; Cognitive Deficiencies
• Intervention / Treatment: Other: Brain MRI - Clinical and cognitive evaluation; Other: Eye movement

Detailed Description

This is a prospective cohort, observational, longitudinal, monocentric study. This study will include 60 patients with CIS followed for 1 year and 60 healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • CHU de Bordeaux

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients:

  • Men and Women
  • ≥16 years
  • Fluent French speaker
  • 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 at least 3 mm, at least one of which being cerebral, ovoid, or periventricular
  • Having a medical insurance
  • Free and informed consent signed

• Controls:

  • Men and Women
  • ≥18 years
  • Fluent French speaker
  • Having a medical insurance
  • Free and informed consent signed

Exclusion Criteria:

• Patients:

  • Prior documented neurological episode suggestive of MS.
  • Other ongoing neurological diseases.
  • Known chronic systemic diseases as judged by the investigator (for instance: lupus, Gougerot-Sjögren, sarcoidosis, sclerodermia, Crohn disease,…).
  • Other causes (trauma, tumor, radiotherapy, infections, vascular diseases, neuromyelitis optica).
  • Current dependence on alcohol or drugs.
  • Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 15 days
  • MRI contra-indications.
  • Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily.

• Controls:

  • Known chronic psychiatric or neurologic diseases which could interfere with neuropsychological testing, not taking into account stable and mild depressive syndrome
  • Known chronic systemic diseases as judged by the investigator (for instance: lupus, Gougerot-Sjögren, sarcoidosis, scleroderma, Crohn disease…).
  • MS familial history
  • Current dependence on alcohol or drugs
  • Known cognitive impairment
  • Prior neuropsychological testing with the same tests less than one year
  • Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 2 months
  • Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily.
  • MRI contra-indications
  • Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control; healthy subject	Other: Brain MRI - Clinical and cognitive evaluation; Clinical evaluation (EDSS, MSFC); Cognitive evaluation with tests of information processing speed, attention, working memory, episodic memory and executive functions, assessment of confounding factors (depression (BDI) and anxiety (HAD), mood (EHD), fatigue (M-FIS) and assessment of quality of life (SEP-59); Brain MRI (3 Tesla): FLAIR, 3D MPRAGE T1 and DTI; Other: Eye movement; Assessment of eye Movements (EyeBrain software) for only the group of 15 healthy subjects at baseline and at 12 months
Experimental: Patient; 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	Other: Brain MRI - Clinical and cognitive evaluation; Clinical evaluation (EDSS, MSFC); Cognitive evaluation with tests of information processing speed, attention, working memory, episodic memory and executive functions, assessment of confounding factors (depression (BDI) and anxiety (HAD), mood (EHD), fatigue (M-FIS) and assessment of quality of life (SEP-59); Brain MRI (3 Tesla): FLAIR, 3D MPRAGE T1 and DTI; Other: Eye movement; Assessment of eye Movements (EyeBrain software) for only the group of 15 healthy subjects at baseline and at 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between fractional anisotropy (FA) value and cognitive z scores or cognitive impairment indexes for each domains	IPS, attention, working memory, episodic memory and executive functions), established by voxel-wise statistics (TBSS) in CIS patients	visit 2 - 1 year after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of skeleton of FA between CIS patients and healthy subjects		V2 - 1 year after the inclusion
Comparison of cognitive scores at each test between CIS patients and controls		D0 and V2 - 1 year after the inclusion
Proportion of patients with cognitive impairment (≥ 3 tests impaired) and correlations with anxiety, depressive syndrome and fatigue		D0 and V2 - 1 year after the inclusion
Comparison of statistical maps of FA	mean cortical thickness and deep grey nuclei volumes with cognitive indexes in the 3 pre-define groups: cognitively preserved CIS patients at baseline and after one year; cognitively impaired CIS patients only after one year and cognitively impaired CIS patients at the two evaluations.	D0 and V2 - 1 year after the inclusion
Correlations between cognitive scores and mean cortical thickness and deep grey nuclei volumes in CIS patients		D0 and V2 - 1 year after the inclusion
Comparison of cognitive scores at each test and eye movements scores		D0 and V2 - 1 year after the inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: TEVA laboratories
• Investigators: Principal Investigator: Bruno BROCHET, Prof, CHU Bordeaux

Publications and helpful links

General Publications

• Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Coupe P, Ouallet JC, Planche V, Moscufo N, Meier DS, Tourdias T, Guttmann CR, Dousset V, Brochet B. Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):146-151. doi: 10.1136/jnnp-2016-313867. Epub 2016 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2012
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: May 24, 2013
• First Posted (Estimate): May 30, 2013

Study Record Updates

• Last Update Posted (Actual): October 3, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Multiple Sclerosis; Sclerosis; Syndrome
• Other Study ID Numbers: CHUBX 2011/33