Cognition Evolution and MRI Markers in PPMS Patients on 2 Years

Not Applicable

Active, not recruiting

• Conditions: Multiple Sclerosis, Primary Progressive
• Interventions: Other: Clinical assessment; Other: Ecological evaluation; Other: Neuropsychological evaluation; Other: Psychological evaluation; Device: MRI Evaluation

• Registration Number: NCT03455582
• Lead Sponsor: University Hospital, Bordeaux

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-04
• Study First Submitted QC: 2018-02-27
• Study First Posted: 2018-03-06
• Study Start: 2018-09-24
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-20
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 66

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
patient	Clinical assessment	PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
patient	MRI Evaluation	PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
Control	Ecological evaluation	40 Healthy controls
patient	Neuropsychological evaluation	PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
patient	Psychological evaluation	PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
Control	MRI Evaluation	40 Healthy controls
patient	Ecological evaluation	PPMS diagnosis according to McDonald 2010 criteria (Polman et al, 2011)
Control	Neuropsychological evaluation	40 Healthy controls
Control	Psychological evaluation	40 Healthy controls

Primary Outcome Measures

Name	Time	Method
Change of composite z cognitive score based on individual neuropsychological scores	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

Secondary Outcome Measures

Name	Time	Method
Changes of composite z ecological score based on individual ecological scores	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.
Change of composite z cognitive score based on individual neuropsychological scores	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.
Correlation of composite z cognitive score and ecological score with MRI parameters reflecting grey and white matter integrity and anatomic/functional connectivity	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.

Trial Locations

Locations (3)

CHU de Limoges; 🇫🇷 Limoges, France

CHU de Bordeaux; 🇫🇷 Bordeaux, France

CHU de Poitiers; 🇫🇷 Poitiers, France