Telerehabilitation of Multidomain Cognitive Impairment in Multiple Sclerosis

NCT05611047 | Terminated

• 1 other identifier: CHUBX 2021/60
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

Treating cognitive impairment (CI) in multiple sclerosis (MS), the leading cause of disability due to nontraumatic neurological disease in young adults, is an important challenge. The contribution of CI to disability in MS has been increasingly recognized, and CI has been shown to decrease health-related quality of life (HR-QOL), even in the early stages of the disease. CI negatively impacts daily activities such as driving, vocational status, absenteeism, and instrumental activities in persons living with MS (PwMS). No medication has proven to have a consistent symptomatic effect on CI in MS, and disease-modifying therapies only have a small impact on CI progression. CI in MS is dominated by a slowdown in information processing speed (IPS), as well as by disturbances of more specific cognitive functions such as attention, episodic memory (EM), working memory (WM) and executive function (EF). The alteration of IPS has consequences for WM, attention, EF and EM. IPS impairment predicts subsequent disability and vocational status and changes in quality of life (QOL). Cognitive rehabilitation (CR) is the most promising approach for treating MS-related CI, as concluded by recent reviews and meta-analyses, despite important methodological shortcomings. Methodological limitations in early studies have led to disappointing results, and well-designed studies are still scarce. As noted recently, many studies lack a randomized controlled design that includes passive or active control conditions, primary neuropsychological end-points identified a priori, evidence of the sustainability of CR and the inclusion of near and far transfer outcomes. Tertiary outcomes of QOL, metacognition, or other patient-reported outcomes (PROs) are rarely used. In view of the results of these different studies, the investigators propose a single-blind randomized controlled trial of a telerehabilitation program for MS associated CI, based on Rehacom software, using appropriates modules according to specific CI, but complemented by individual remote online rehabilitation sessions allowing a better adaptation of the program to the patient's deficit, a more efficient supervision and meta-cognitive work. This program will be evaluated in terms of effectiveness on neuropsychological tests, effectiveness on specific cognitive domains re-educated according to the impairments detected in the baseline, an ecological evaluation and the impact on daily cognitive functioning. Specific active rehabilitation will be compared to a placebo intervention of the same duration and intensity. Only a multi-center study will make it possible to achieve sufficient number of patients to meet these objectives.

Conditions

Multiple Sclerosis

Keywords

Autoimmune Diseases of the Nervous System; Demyelinating Autoimmune Diseases; Demyelinating Diseases; Immune System Diseases; Nervous System Diseases; Pathologic Processes; cognitive impairment; ecological assessment; telerehabilitation

Outcome Measures

Primary Outcomes (1)

• Improvement of two of the four reaction time z scores over the 12 weeks of training in the ecological assessment of cognitive impairment (CI) using the Urban DailyCog®.

  12 weeks after baseline (Day 0)

Secondary Outcomes (13)

• Change in the neuropsychological tests raw scores between baseline (W0) and after rehabilitation (W12) between the two groups

  12 weeks after baseline (Day 0)

• Change in the neuropsychological tests raw scores between visit W12 and visit W24 between the two groups.

  24 weeks after baseline (Day 0)

• Change in information processing speed (IPS), composite z scores between W0-W12 and W12-W24

  24 weeks after baseline (Day 0)

• Change in attention and working memory (WM) domain neuropsychological tests composite z scores and raw scores between W0-W12 and W12-W24 in subgroups of patients affected for these domains

  24 weeks after baseline (Day 0)

• Change in the sum of the 4 reaction time differences over the 12 weeks of training in the ecological assessment of CI using the Urban DailyCog®.

  12 weeks after baseline (Day 0)

Study Arms (2)

Active cognitive rehabilitation

EXPERIMENTAL

Other: Clinical assessment; Other: Classical cognitive evaluation of several domains:; Other: Ecological evaluation; Behavioral: Patent reported outcomes (PRO's); Other: Telerehabilitation : active procedure

Sham cognitive rehabilitation

ACTIVE COMPARATOR

Other: Clinical assessment; Other: Classical cognitive evaluation of several domains:; Other: Ecological evaluation; Behavioral: Patent reported outcomes (PRO's); Other: Telerehabilitation : comparator procedure

Interventions

Clinical assessment OTHER

MS history and MS treatments and Expanded Disability Status Scale (EDSS) score will be recorded

Active cognitive rehabilitation; Sham cognitive rehabilitation

Classical cognitive evaluation of several domains: OTHER

Information processing speed (IPS) Working memory (WM) Executive functions (EF) Episodic memory (EM) Premorbid intelligence quotient (IQ) Multidomain or complex task

Active cognitive rehabilitation; Sham cognitive rehabilitation

Ecological evaluation OTHER

Virtual reality task : Urban DailyCog©

Active cognitive rehabilitation; Sham cognitive rehabilitation

Patent reported outcomes (PRO's) BEHAVIORAL

Patent reported outcomes (PRO's) : Beck Depression Inventory (BDI), European Quality of Life-5 Dimensions (EQ-5D-5L) for Health-Related Quality of Life (HRQOL), Multiple Sclerosis Impact Scale-29 Items (MSIS-29), French version of the Modified Fatigue Impact Scale (EMISEP) and State trait anxiety inventory (STAI). Subjective cognitive deficits: Perceived Deficits Questionnaire (PDQ) and Cognitive Activities Questionnaire (DCAQ)

Active cognitive rehabilitation; Sham cognitive rehabilitation

Telerehabilitation : active procedure OTHER

The Cognitive rehabilitation (CR) consists of weekly 45 minutes online individual session with the unblinded Speech Therapist.

Active cognitive rehabilitation

Telerehabilitation : comparator procedure OTHER

Once per week over a 12-week period completed by daily online exercises performed by the patient 4 days a week.

Sham cognitive rehabilitation

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female;
• Age 18-55 years;
• Native French speaking;
• Definite diagnosis of Relapsing-remitting MS (RRMS) according to McDonald 2017 criteria;
• Disease duration\> 12 months and ≤ 15 years;
• Computerized-Screening Cognitive Test (CSCT) score ≤ - 1.282 Standard Deviations (SD) (10th percentile) and/or cognitive complaint;
• scores -1 SDa or 2 scores -1.5 SDb at least 2 of 5 baseline preselection neuropsychological battery tests in one of the following domains: processing speed or attention or working memory (SDMT, subtests alert, divided attention, visual scanning for selective attention, TAP and subtest working memory of the WAIS IV) and SDMT score not ≤ -3 SD;
• Able to use a computer with Windows operating system, an internet connection;
• Being affiliated to health insurance

You may not qualify if:

• Previous history of other neurological disease;
• Psychiatric comorbidity including severe depression according to Diagnostic and Statistical Manual-IV (DSM-IV);
• Current dependence on alcohol or other addiction to toxic;
• Disabling visual or motor problems preventing participation to neuropsychological assessments;
• Change of psychotropic drug or disease-modifying therapies since less than one month;
• Illiteracy, ie: unable to count or to read;
• Acquisition disorders: dyslexia, dysphasia, dyscalculia and dyspraxia;
• 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).

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Celgene: collaborator

Study Sites (7)

CHU de Bordeaux - Service de neurologie

Bordeaux, France

Location

CHU de Clermont-Ferrand - Service de neurologie

Clermont-Ferrand, France

Location

CHU de Dijon-Bourgogne - Service de neurologie

Dijon, France

Location

CH de Dunkerque - Service de neurologie

Dunkirk, France

Location

Hôpital Saint Vincent de Paul - Service de neurologie

Lille, France

Location

CHU de Montpellier - Service de neurologie

Montpellier, France

Location

CHI Hôpital de Poissy Saint Germain en Laye - Service de neurologie

Poissy, France

Location

MeSH Terms

Conditions

Multiple Sclerosis; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Immune System Diseases; Nervous System Diseases; Pathologic Processes; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases; 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: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: November 9, 2022
• Study Start: February 21, 2023
• Primary Completion: February 19, 2025
• Study Completion: February 19, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)