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Cognition Evolution and MRI Markers in PPMS Patients on 2 Years (PRO-COG)

Primary Purpose

Multiple Sclerosis, Primary Progressive

Status
Recruiting
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, Primary Progressive focused on measuring cognitive impairment, ecological assessment, brain MRI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

PATIENTS

  • Male or female;
  • Age ≥ 18 years;
  • PPMS diagnosis according to McDonald 2010 criteria;
  • Disease duration ≤ 15 years;
  • Native French speaking;
  • Being affiliated to health insurance;
  • Willing to participate and to sign informed consent.

HEALTHY CONTROLS

  • Male or Female;
  • Age ≥ 18 years;
  • Native French speaking;
  • Being affiliated to health insurance;
  • Willing to participate and to sign informed consent.

Exclusion Criteria:

PATIENTS

  • previous history of other neurological disease;
  • 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;
  • change of psychotropic drug since less than one month;
  • 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;
  • family history of MS;
  • psychiatric comorbidity including severe depression according to DSM-IV;
  • alcohol or other toxic addiction;
  • psychotropic drugs; known cognitive complaint or neuropsychological affection;
  • prior neuropsychological testing with the same tests less than 6 months
  • contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, meta 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 BordeauxRecruiting
  • CHU de LimogesRecruiting
  • CHU de PoitiersRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

patient

Control

Arm Description

PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)

40 Healthy controls

Outcomes

Primary 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 (baseline and 2 years). 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

Secondary Outcome Measures

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 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. The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests.
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.
Changes of composite z ecological score based on individual ecological 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. The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests.

Full Information

First Posted
January 4, 2018
Last Updated
March 10, 2023
Sponsor
University Hospital, Bordeaux
Collaborators
Roche Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT03455582
Brief Title
Cognition Evolution and MRI Markers in PPMS Patients on 2 Years
Acronym
PRO-COG
Official Title
Longitudinal Study of Cognition in Primary Progressive Multiple Sclerosis: a Cohort Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 24, 2018 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
Roche Pharma AG

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. Cognitive disorders frequency in MS is estimated between 40 and 60%. Cognitive impairment affects quality of life and vocational status in MS patients. Until recently, little information was available on the cognitive dysfunction and their evolution that occur in primary progressive multiple sclerosis (PPMS) as compared with relapsing-remitting MS (RRMS). In PPMS pathological studies have shown the importance of cortical demyelination and meningeal inflammation suggesting that the GM alteration could play a major role in the cognitive impairment in this phenotype. The cognitive evolution and the brain tissue alteration at the origin of these difficulties remain poorly understood in PPMS. The use of new techniques for morphological and functional MRI can study the contribution of diffuse White Matter (WM) alteration (probably through disconnexion of relevant network) and diffuse Grey matter (GM) alterations in the cerebral cortex and other structures (the hippocampi, the cerebellum, and the thalami) in cognitive impairment in PPMS patients and on their evolution.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Primary Progressive
Keywords
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
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
patient
Arm Type
Experimental
Arm Description
PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
Arm Title
Control
Arm Type
Active Comparator
Arm Description
40 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)
Ecological evaluation
Intervention Description
Virtual reality task 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 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 (baseline and 2 years). 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
Secondary Outcome Measure Information:
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 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. The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests.
Time Frame
At baseline (day 0) and at 24 months from baseline
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.
Time Frame
At baseline (day 0), at 12 months and at 24 months from baseline
Title
Changes of composite z ecological score based on individual ecological 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. The composite z ecological score is the average of z ecological scores of virtual reality task (Urban DailyCog©) and actual reality tests.
Time Frame
At baseline (day 0), at 12 months and at 24 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: PATIENTS Male or female; Age ≥ 18 years; PPMS diagnosis according to McDonald 2010 criteria; Disease duration ≤ 15 years; Native French speaking; Being affiliated to health insurance; Willing to participate and to sign informed consent. HEALTHY CONTROLS Male or Female; Age ≥ 18 years; Native French speaking; Being affiliated to health insurance; Willing to participate and to sign informed consent. Exclusion Criteria: PATIENTS previous history of other neurological disease; 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; change of psychotropic drug since less than one month; 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; family history of MS; psychiatric comorbidity including severe depression according to DSM-IV; alcohol or other toxic addiction; psychotropic drugs; known cognitive complaint or neuropsychological affection; prior neuropsychological testing with the same tests less than 6 months contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, meta 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aurélie RUET, Prof
Phone
05 56 79 55 21
Ext
+33
Email
aurelie.ruet@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Mathilde DELOIRE, PhD
Phone
05 57 82 12 75
Ext
+33
Email
mathilde.deloire@chu-bordeaux.fr
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
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurelie RUET, Prof
Phone
05 56 79 55 21
Ext
+33
Email
aurelie.ruet@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Mathilde DELOIRE, PhD
Phone
05 57 82 12 75
Ext
+33
Email
mathilde.deloire@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Bruno BROCHET, Prof
First Name & Middle Initial & Last Name & Degree
Aurélie RUET, Prof
Facility Name
CHU de Limoges
City
Limoges
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent MAGY, Prof
Email
laurent.magy@unilim.fr
First Name & Middle Initial & Last Name & Degree
Laurent MAGY, Prof
Facility Name
CHU de Poitiers
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Philippe NEAU, Prof
Email
jph.neau@chu-poitiers.fr
First Name & Middle Initial & Last Name & Degree
Jean-Philippe NEAU, Prof

12. IPD Sharing Statement

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Cognition Evolution and MRI Markers in PPMS Patients on 2 Years

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