<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03768648</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2016/02</org_study_id>
    <nct_id>NCT03768648</nct_id>
  </id_info>
  <brief_title>Cognition and MRI Markers in MS Patients With Aubagio® Treatment</brief_title>
  <acronym>AUBACOG</acronym>
  <official_title>Everyday Life Cognition and Non-conventional Magnetic Resonance Markers in RRMS Patients Treated With Aubagio® in a Real-life Setting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Bordeaux</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cognitive impairment is nowadays more and more recognized as an important feature of the&#xD;
      multiple sclerosis (MS) disease which contributes largely to disability. Cognitive assessment&#xD;
      using classical neuropsychological tests are poorly correlated with patient's complaints and&#xD;
      daily functioning. Ecological evaluations, recent and innovative way to assess cognitive&#xD;
      functions with the true impact of cognitive impairment in everyday daily life of patients.&#xD;
      One goal of an ecological test could be to identify MS patients in whom cognitive impairment&#xD;
      has a strong interaction with daily life. Different type of ecological evaluation have been&#xD;
      recently proposed in MS, including assessment cognitive tasks in a virtual reality&#xD;
      environment using the Urban DailyCog® software developed in our laboratory (Hamel et al,&#xD;
      2015). Virtual reality environment assessments are promising in detecting cognitive&#xD;
      impairment while providing friendly assessments for patients and simulating daily activities.&#xD;
      . Cognitive dysfunction is correlated with white matter diffuse injury in relapsing-remitting&#xD;
      MS (RRMS) patients and brain atrophy However, the relationships between structural brain&#xD;
      damage and brain connectivity with cognitive functioning assessed by ecological evaluation&#xD;
      are also unknown. The use of new techniques for morphological and functional MRI can study&#xD;
      the contribution of diffuse white matter (WM) alteration and diffuse gray matter (GM)&#xD;
      alterations in cognitive impairment and on their evolution.&#xD;
&#xD;
      The objectives are to evaluate the ecological assessment (Urban DailyCog® and actual reality)&#xD;
      to detect cognitive impairment in everyday daily life of patients and their changes and to&#xD;
      investigate structural WM and GM damages and the dynamic of functional connectivity for&#xD;
      explaining and predicting cognitive disability during two years in RRMS patients treated by&#xD;
      the same treatment Aubagio®.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 21, 2019</start_date>
  <completion_date type="Actual">February 23, 2023</completion_date>
  <primary_completion_date type="Actual">February 23, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of composite z ecological score based on individual ecological scores.</measure>
    <time_frame>At baseline (day 0) and at 24 months from baseline</time_frame>
    <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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of composite z cognitive score based on individual neuropsychological scores</measure>
    <time_frame>At baseline (day 0) and at 24 months from baseline</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of composite z cognitive score and ecological score with MRI parameters reflecting grey and white matter integrity and anatomic/functional connectivity</measure>
    <time_frame>At baseline (day 0) and at 24 months from baseline</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Multiple Sclerosis, Relapsing-Remitting</condition>
  <arm_group>
    <arm_group_label>patient</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RRMS diagnosis according to McDonald criteria (Polman et al.,2005);</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>40 Healthy controls (HC)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical assessment</intervention_name>
    <description>EDSS (Kurtzke JF; 1983) and the modified MS functional composite (MSFC) score. MS history and MS treatment will be recorded</description>
    <arm_group_label>patient</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ecological evaluation</intervention_name>
    <description>Virtual reality task : Urban DailyCog© and Actual reality</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>patient</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Neuropsychological evaluation</intervention_name>
    <description>cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>patient</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Psychological evaluation</intervention_name>
    <description>questionnaires for depression, anxiety and fatigue</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>patient</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI Evaluation</intervention_name>
    <description>morphological MRI and resting state functional MRI (fMRI)</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>patient</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        PATIENTS&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Age 18-60 years&#xD;
&#xD;
          -  RRMS diagnosis according to McDonald criteria (Polman et al., 2005);&#xD;
&#xD;
          -  Treated with Aubagio® (Indication for first line therapy)&#xD;
&#xD;
          -  Native French speaking&#xD;
&#xD;
          -  Being affiliated to health insurance&#xD;
&#xD;
          -  Having signed an informed consent (at the latest on the day of inclusion and before&#xD;
             any examination required by research)&#xD;
&#xD;
        HEALTHY CONTROLS&#xD;
&#xD;
          -  Male or Female,&#xD;
&#xD;
          -  Age 18-60 years&#xD;
&#xD;
          -  Willing to participate and to sign informed consent.&#xD;
&#xD;
          -  Being affiliated to health insurance&#xD;
&#xD;
          -  Having signed an informed consent (at the latest on the day of inclusion and before&#xD;
             any examination required by research)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        PATIENTS&#xD;
&#xD;
          -  History of neurological disease and/or other neurological diseases,&#xD;
&#xD;
          -  Psychiatric comorbidity including severe depression according to DSM-IV,&#xD;
&#xD;
          -  Alcohol or other addiction to toxic,&#xD;
&#xD;
          -  Disabling visual or motor problems preventing participation to neuropsychological&#xD;
             assessments,&#xD;
&#xD;
          -  Acquisition disorders : Dyslexia, Dysphasia, Dyscalculia and dyspraxia,&#xD;
&#xD;
          -  Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment&#xD;
             less than 30 days&#xD;
&#xD;
          -  Relapse since less than one month,&#xD;
&#xD;
          -  Steroid treatment less than one month (be taken orally or by infusion) at the dosage&#xD;
             of 500mg daily,&#xD;
&#xD;
          -  Prior neuropsychological testing with the same tests less than 6 months&#xD;
&#xD;
          -  Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear&#xD;
             implants, metal fragments or foreign objects in the eyes, skin or body,&#xD;
             claustrophobia) or refusing MRI&#xD;
&#xD;
          -  Illiteracy, is unable to count or to read&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty&#xD;
             by a judicial or administrative decision, minors, persons of legal age who are the&#xD;
             object of a legal protection measure or unable to express their consent)&#xD;
&#xD;
        HEALTHY CONTROLS&#xD;
&#xD;
          -  History of neurological disease and/or neurological diseases&#xD;
&#xD;
          -  Psychiatric comorbidity including severe depression according to DSM-IV;&#xD;
&#xD;
          -  Alcohol or other toxic addiction;&#xD;
&#xD;
          -  Known cognitive complaint or neuropsychological affection&#xD;
&#xD;
          -  Hypnotic or anxiolytic or antidepressive treatment,&#xD;
&#xD;
          -  Prior neuropsychological testing with the same tests less than 6 months&#xD;
&#xD;
          -  Acquisition disorders: Dyslexia, Dysphasia, Dyscalculia and dyspraxia,&#xD;
&#xD;
          -  Steroid treatment less than one month (be taken orally or by infusion) at the dosage&#xD;
             of 500mg daily,&#xD;
&#xD;
          -  Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear&#xD;
             implants, metal fragments or foreign objects in the eyes, skin or body,&#xD;
             claustrophobia) or refusing MRI&#xD;
&#xD;
          -  Illiteracy, is unable to count or to read&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Person concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty&#xD;
             by a judicial or administrative decision, minors, persons of legal age who are the&#xD;
             object of a legal protection measure or unable to express their consent)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aurélie RUET, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Bordeaux</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Bordeaux - Service de neurologie</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autoimmune Diseases of the Nervous System</keyword>
  <keyword>Demyelinating Autoimmune Diseases, CNS</keyword>
  <keyword>Demyelinating Diseases</keyword>
  <keyword>Immune System Diseases</keyword>
  <keyword>Nervous System Diseases</keyword>
  <keyword>Pathologic Processes</keyword>
  <keyword>cognitive impairment</keyword>
  <keyword>ecological assessment</keyword>
  <keyword>brain MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03768648
org study id: CHUBX 2016/02
nct id: NCT03768648
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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®.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Change of composite z ecological score based on individual ecological scores.
time frame: At baseline (day 0) and at 24 months from baseline
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).
measure: Change of composite z cognitive score based on individual neuropsychological scores
time frame: At baseline (day 0) and at 24 months from baseline
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.
measure: Correlation of composite z cognitive score and ecological score with MRI parameters reflecting grey and white matter integrity and anatomic/functional connectivity
time frame: At baseline (day 0) and at 24 months from baseline
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.
arm group label: patient
arm group type: Experimental
description: RRMS diagnosis according to McDonald criteria (Polman et al.,2005);
arm group label: Control
arm group type: Active Comparator
description: 40 Healthy controls (HC)
intervention type: Other
intervention name: Clinical assessment
description: EDSS (Kurtzke JF; 1983) and the modified MS functional composite (MSFC) score. MS history and MS treatment will be recorded
arm group label: patient
intervention type: Other
intervention name: Ecological evaluation
description: Virtual reality task : Urban DailyCog© and Actual reality
arm group label: Control
arm group label: patient
intervention type: Other
intervention name: Neuropsychological evaluation
description: cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function
arm group label: Control
arm group label: patient
intervention type: Other
intervention name: Psychological evaluation
description: questionnaires for depression, anxiety and fatigue
arm group label: Control
arm group label: patient
intervention type: Device
intervention name: MRI Evaluation
description: morphological MRI and resting state functional MRI (fMRI)
arm group label: Control
arm group label: patient
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Aurélie RUET, Prof
role: Principal Investigator
affiliation: CHU Bordeaux
facility: 
country: France
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting