search
Back to results

Cognition and MRI Markers in MS Patients With Aubagio® Treatment (AUBACOG)

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Clinical assessment
Ecological evaluation
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, Relapsing-Remitting focused on measuring Autoimmune Diseases of the Nervous System, Demyelinating Autoimmune Diseases, CNS, Demyelinating Diseases, Immune System Diseases, Nervous System Diseases, Pathologic Processes, cognitive impairment, ecological assessment, brain MRI

Eligibility Criteria

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

Inclusion Criteria:

PATIENTS

  • Male or female
  • Age 18-60 years
  • RRMS diagnosis according to McDonald criteria (Polman et al., 2005);
  • Treated with Aubagio® (Indication for first line therapy)
  • Native French speaking
  • Being affiliated to health insurance
  • Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research)

HEALTHY CONTROLS

  • Male or Female,
  • Age 18-60 years
  • Willing to participate and to sign informed consent.
  • Being affiliated to health insurance
  • Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research)

Exclusion Criteria:

PATIENTS

  • History of neurological disease and/or other neurological diseases,
  • Psychiatric comorbidity including severe depression according to DSM-IV,
  • 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
  • Relapse since less than one month,
  • Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily,
  • Prior neuropsychological testing with the same tests less than 6 months
  • 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, 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 comorbidity including severe depression according to DSM-IV;
  • Alcohol or other toxic addiction;
  • Known cognitive complaint or neuropsychological affection
  • Hypnotic or anxiolytic or antidepressive treatment,
  • Prior neuropsychological testing with the same tests less than 6 months
  • Acquisition disorders: Dyslexia, Dysphasia, Dyscalculia and dyspraxia,
  • 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, is unable to count or to read
  • Pregnant or breastfeeding women
  • Person 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

patient

Control

Arm Description

RRMS diagnosis according to McDonald criteria (Polman et al.,2005);

40 Healthy controls (HC)

Outcomes

Primary Outcome Measures

Change of composite z ecological score based on individual ecological scores.
The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time (baseline and 2 years).

Secondary Outcome Measures

Change of composite z cognitive score based on individual neuropsychological scores
The composite z cognitive score is the average of z individual cognitive scores. The score from each cognitive test is transformed into z-scores. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time. Individual neuropsychological scores included in composite z cognitive score : the Alertness subtest, the divided attention subtest and the visual-scanning subtest from the TAP, The Symbol-digit-modalities-test, the Paced-Auditory-Serial-Addition-Test 3s, reversed span, the Stroop test, the Verbal fluency, Trail Making test, the California Verbal memory learning test and the Brief visual memory test -revised.
Correlation of composite z cognitive score and ecological score with MRI parameters reflecting grey and white matter integrity and anatomic/functional connectivity
The composite z cognitive score and the composite ecological score are the average of z individual cognitive and ecological scores. The score from each cognitive and ecological test is transformed into z-scores. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time.

Full Information

First Posted
December 4, 2018
Last Updated
March 7, 2023
Sponsor
University Hospital, Bordeaux
Collaborators
Genzyme, a Sanofi Company
search

1. Study Identification

Unique Protocol Identification Number
NCT03768648
Brief Title
Cognition and MRI Markers in MS Patients With Aubagio® Treatment
Acronym
AUBACOG
Official Title
Everyday Life Cognition and Non-conventional Magnetic Resonance Markers in RRMS Patients Treated With Aubagio® in a Real-life Setting
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
May 21, 2019 (Actual)
Primary Completion Date
February 23, 2023 (Actual)
Study Completion Date
February 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
Genzyme, a Sanofi Company

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
Cognitive impairment is nowadays more and more recognized as an important feature of the multiple sclerosis (MS) disease which contributes largely to disability. Cognitive assessment using classical neuropsychological tests are poorly correlated with patient's complaints and daily functioning. Ecological evaluations, recent and innovative way to assess cognitive functions with the true impact of cognitive impairment in everyday daily life of patients. One goal of an ecological test could be to identify MS patients in whom cognitive impairment has a strong interaction with daily life. Different type of ecological evaluation have been recently proposed in MS, including assessment cognitive tasks in a virtual reality environment using the Urban DailyCog® software developed in our laboratory (Hamel et al, 2015). Virtual reality environment assessments are promising in detecting cognitive impairment while providing friendly assessments for patients and simulating daily activities. . Cognitive dysfunction is correlated with white matter diffuse injury in relapsing-remitting MS (RRMS) patients and brain atrophy However, the relationships between structural brain damage and brain connectivity with cognitive functioning assessed by ecological evaluation are also unknown. The use of new techniques for morphological and functional MRI can study the contribution of diffuse white matter (WM) alteration and diffuse gray matter (GM) alterations in cognitive impairment and on their evolution. The objectives are to evaluate the ecological assessment (Urban DailyCog® and actual reality) to detect cognitive impairment in everyday daily life of patients and their changes and to investigate structural WM and GM damages and the dynamic of functional connectivity for explaining and predicting cognitive disability during two years in RRMS patients treated by the same treatment Aubagio®.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
Keywords
Autoimmune Diseases of the Nervous System, Demyelinating Autoimmune Diseases, CNS, Demyelinating Diseases, Immune System Diseases, Nervous System Diseases, Pathologic Processes, cognitive impairment, ecological assessment, brain MRI

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
patient
Arm Type
Experimental
Arm Description
RRMS diagnosis according to McDonald criteria (Polman et al.,2005);
Arm Title
Control
Arm Type
Active Comparator
Arm Description
40 Healthy controls (HC)
Intervention Type
Other
Intervention Name(s)
Clinical assessment
Intervention Description
EDSS (Kurtzke JF; 1983) and the modified MS functional composite (MSFC) score. MS history and MS treatment will be recorded
Intervention Type
Other
Intervention Name(s)
Ecological evaluation
Intervention Description
Virtual reality task : Urban DailyCog© and Actual reality
Intervention Type
Other
Intervention Name(s)
Neuropsychological evaluation
Intervention Description
cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function
Intervention Type
Other
Intervention Name(s)
Psychological evaluation
Intervention Description
questionnaires for depression, anxiety and fatigue
Intervention Type
Device
Intervention Name(s)
MRI Evaluation
Intervention Description
morphological MRI and resting state functional MRI (fMRI)
Primary Outcome Measure Information:
Title
Change of composite z ecological score based on individual ecological scores.
Description
The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time (baseline and 2 years).
Time Frame
At baseline (day 0) and at 24 months from baseline
Secondary Outcome Measure Information:
Title
Change of composite z cognitive score based on individual neuropsychological scores
Description
The composite z cognitive score is the average of z individual cognitive scores. The score from each cognitive test is transformed into z-scores. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time. Individual neuropsychological scores included in composite z cognitive score : the Alertness subtest, the divided attention subtest and the visual-scanning subtest from the TAP, The Symbol-digit-modalities-test, the Paced-Auditory-Serial-Addition-Test 3s, reversed span, the Stroop test, the Verbal fluency, Trail Making test, the California Verbal memory learning test and the Brief visual memory test -revised.
Time Frame
At baseline (day 0) and at 24 months from baseline
Title
Correlation of composite z cognitive score and ecological score with MRI parameters reflecting grey and white matter integrity and anatomic/functional connectivity
Description
The composite z cognitive score and the composite ecological score are the average of z individual cognitive and ecological scores. The score from each cognitive and ecological test is transformed into z-scores. Z-scores will be calculated for each cognitive score with the following formula: (patient's score - mean value of HC group matched for age, sex, and education level)/standard deviation of the matched HC for each evaluation time.
Time Frame
At baseline (day 0) and at 24 months from baseline

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 Male or female Age 18-60 years RRMS diagnosis according to McDonald criteria (Polman et al., 2005); Treated with Aubagio® (Indication for first line therapy) Native French speaking Being affiliated to health insurance Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research) HEALTHY CONTROLS Male or Female, Age 18-60 years Willing to participate and to sign informed consent. Being affiliated to health insurance Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research) Exclusion Criteria: PATIENTS History of neurological disease and/or other neurological diseases, Psychiatric comorbidity including severe depression according to DSM-IV, 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 Relapse since less than one month, Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily, Prior neuropsychological testing with the same tests less than 6 months 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, 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 comorbidity including severe depression according to DSM-IV; Alcohol or other toxic addiction; Known cognitive complaint or neuropsychological affection Hypnotic or anxiolytic or antidepressive treatment, Prior neuropsychological testing with the same tests less than 6 months Acquisition disorders: Dyslexia, Dysphasia, Dyscalculia and dyspraxia, 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, is unable to count or to read Pregnant or breastfeeding women Person 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, Prof
Organizational Affiliation
CHU Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux - Service de neurologie
City
Bordeaux
Country
France

12. IPD Sharing Statement

Learn more about this trial

Cognition and MRI Markers in MS Patients With Aubagio® Treatment

We'll reach out to this number within 24 hrs