Cognition Evolution and MRI Markers in PPMS Patients on 2 Years

NCT03455582 | Active Not Recruiting

• 1 other identifier: CHUBX 2017/14
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple Sclerosis, Primary Progressive

Keywords

cognitive impairment; ecological assessment; brain MRI

Outcome Measures

Primary Outcomes (1)

• 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

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

Secondary Outcomes (3)

• 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

• Change of composite z cognitive score based on individual neuropsychological scores

  At baseline (day 0), at 12 months and at 24 months from baseline

• Changes of composite z ecological score based on individual ecological scores

  At baseline (day 0), at 12 months and at 24 months from baseline

Study Arms (2)

patient

EXPERIMENTAL

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

Other: Clinical assessment; Other: Ecological evaluation; Other: Neuropsychological evaluation; Other: Psychological evaluation; Device: MRI Evaluation

Control

ACTIVE COMPARATOR

40 Healthy controls

Other: Ecological evaluation; Other: Neuropsychological evaluation; Other: Psychological evaluation; Device: MRI Evaluation

Interventions

Clinical assessment OTHER

Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded.

patient

Ecological evaluation OTHER

Virtual reality task and Actual reality

Control; patient

Neuropsychological evaluation OTHER

cognitive tests exploring information processing speed, attention/concentration, working and episodic memories and executive function

Control; patient

Psychological evaluation OTHER

questionnaires for depression, anxiety and fatigue

Control; patient

MRI Evaluation DEVICE

morphological MRI and resting state functional MRI (fMRI)

Control; patient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Roche Pharma AG: collaborator

Study Sites (3)

CHU de Bordeaux

Bordeaux, France

Location

CHU de Limoges

Limoges, France

Location

CHU de Poitiers

Poitiers, France

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Aurélie RUET, Prof

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: March 6, 2018
• Study Start: September 24, 2018
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

FR (3)