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

March 10, 2023 updated by: University Hospital, Bordeaux

Longitudinal Study of Cognition in Primary Progressive Multiple Sclerosis: a Cohort Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France
      • Limoges, France
        • Recruiting
        • CHU de Limoges
        • Contact:
        • Principal Investigator:
          • Laurent MAGY, Prof
      • Poitiers, France
        • Recruiting
        • CHU de Poitiers
        • Contact:
        • Principal Investigator:
          • Jean-Philippe NEAU, Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patient
PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
Other: Clinical assessment
Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded.
Other: Ecological evaluation
Virtual reality task and Actual reality
Other: Neuropsychological evaluation
cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function
Other: Psychological evaluation
questionnaires for depression, anxiety and fatigue
Device: MRI Evaluation
morphological MRI and resting state functional MRI (fMRI)
Active Comparator: Control
40 Healthy controls
Other: Ecological evaluation
Virtual reality task and Actual reality
Other: Neuropsychological evaluation
cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function
Other: Psychological evaluation
questionnaires for depression, anxiety and fatigue
Device: MRI Evaluation
morphological MRI and resting state functional MRI (fMRI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of composite z cognitive score based on individual neuropsychological scores
Time Frame: At baseline (day 0) and at 24 months from baseline

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
At baseline (day 0) and at 24 months from baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

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.
At baseline (day 0) and at 24 months from baseline
Change of composite z cognitive score based on individual neuropsychological scores
Time Frame: At baseline (day 0), at 12 months and at 24 months from baseline
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.
At baseline (day 0), at 12 months and at 24 months from baseline
Changes of composite z ecological score based on individual ecological scores
Time Frame: At baseline (day 0), at 12 months and at 24 months from baseline
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.
At baseline (day 0), at 12 months and at 24 months from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Aurélie RUET, Prof, CHU Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2018

Primary Completion (Anticipated)

March 1, 2026

Study Completion (Anticipated)

March 1, 2026

Study Registration Dates

First Submitted

January 4, 2018

First Submitted That Met QC Criteria

February 27, 2018

First Posted (Actual)

March 6, 2018

Study Record Updates

Last Update Posted (Actual)

March 13, 2023

Last Update Submitted That Met QC Criteria

March 10, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2017/14

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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