Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis

NCT01207856 | Completed

• 1 other identifier: CHUBX 2010/07
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the need for cognitive rehabilitation, there is a paucity of well-designed research studies to investigate treatment approaches or their effectiveness in MS. Most of published studies suffer from significant methodological flaws including small sample size, short follow-up periods, and lack of specific outcome criteria to determine improvement. O'Brien et al. (2008) recently reviewed 16 studies of cognitive rehabilitation designed to persons with MS and found only 4 class I studies and only one class I study of rehabilitation of attention deficits. Methodologically rigorous research is needed to confirm the preliminary results reported by these studies and determine the effectiveness and efficacy of cognitive rehabilitation interventions in attention deficits in MS. O'Brien et al. listed limitations found in previous studies that must be addressed in future studies. The present study was designed according to these recommendations. It is a randomized, controlled study, in parallel groups, evaluator blinded. Number of participants: 25 RRMS patients in the active group, 25 RRMS patients in the control group and 25 healthy subjects. The protocol will be proposed to RRMS patients AFFILIATED TO FRENCH SOCIAL SECURITY referred to the investigators center by practicing neurologists and fulfilling the inclusion criteria for screening. Patients will be randomised between two groups. The active group (25 patients) will be treated by rehabilitation. Individual rehabilitation procedures will be focused on attention, executive functions and IPS. The program will be tailored to each patient cognitive status depending on the impairments identified during the initial assessment while maintaining a systematic work on attention and executive functions. A total of 50 sessions lasting one hour at a rate of 3 sessions per week for a total period of 4 months will be proposed. Patients randomized in the other group will participate to group session every week without specific cognitive rehabilitation. 25 healthy control subjects (group C), matched to patients for education, gender and age with patients of groups A/B will have the same evaluation procedures than patients. Evaluation will be performed at baseline, after 4 months (end of treatment period) and after 8 months. Evaluation will include clinical testing, cognitive battery (paper/pencil and computer tests), cognitive ecological evaluation (Computer test of attention in a virtual reality environment and driving test on a driving simulator), questionnaires about daily life and MRI (fMRI and MRI). All patients and healthy subjects will undergo the fMRI protocol using a paradigm previously published by the investigators group (Bonnet et al., 2009): Go/No-go paradigm with increasing difficulty during four successive conditions (the Tonic Alertness task, Go/No-go (IG), reversal Go/No-go (RG), and complex Go/No-go (CG). In a previous study the investigators observed compensatory activation in MS patients as compared to healthy controls for the three first conditions and a saturation of compensatory processes for the more complex. In the present study, the investigators hypothesize that a similar pattern will occur at baseline and that cognitive rehabilitation will improve brain compensation at the fourth level of complexity.

Conditions

Multiple Sclerosis; Cognitive Rehabilitation

Keywords

Multiple sclerosis; functional MRI; cognitive rehabilitation; ecological evaluation; neuroplasticity

Outcome Measures

Primary Outcomes (1)

• Comparison between groups concerning the z cognitive global executive z score .

  after 4 months (M4)

Secondary Outcomes (5)

• Comparison of brain activation in the treated group versus control group at the fourth condition.

  4 and 8 months

• Comparison between groups concerning the z score of the SDMT

  4 and 8 months

• Comparison between groups of the daily-life cognitive questionnaire scores

  at M4 and M8

• Comparison between groups concerning the z cognitive global executive z score

  8 months

• Clinical Global impression of patients

  4 and 8 months

Study Arms (3)

group A

ACTIVE COMPARATOR

specific cognitive rehabilitation

Behavioral: specific cognitive rehabilitation

Groupe B : non specific rehabilitation

ACTIVE COMPARATOR

Behavioral: non specific cognitive rehabilitation

group C

OTHER

group C for MRI, neuropsychological and ecological assessments

Other: no intervention

Interventions

specific cognitive rehabilitation BEHAVIORAL

Individual rehabilitation procedures will be focused on attention, executive functions, IPS and working memory. The program will be tailored to each patient cognitive status depending on the impairments identified during the initial assessment while maintaining a systematic work on attention and executive functions. A total of 50 sessions lasting one hour at a rate of 3 sessions per week for a total period of 4 months will be proposed. Sessions will include varied exercises according to complexity and presentation modality, using computerized and "paper-and-pencil" tasks and metacognitive training. Work will be progressive, depending on the progresses achieved (increase complexity and intensity of the exercises according to success at the previous level of exercises).

group A

non specific cognitive rehabilitation BEHAVIORAL

A total of 50 sessions lasting one hour at a rate of 3 sessions per week for a total period of 4 months will be proposed by group composed to 5 patients

Groupe B : non specific rehabilitation

no intervention OTHER

no intervention

group C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• patients
• male or female relapsing remitting or secondary progressive or primary progressive Multiple sclerosis patients according to Polman et al. (2005),
• age 18-55; disease duration \>6 months and ≤15 years,
• right handed,
• scores \<1 standard deviation (SD) on the scores evaluating information processing speed and attention (IPS-Attention) and 1 score \<1DS on other tests assessing executive functions (EF) and working memory (WM).
• if they performed worse than 2 scores \<1 SD on the 5 tests of information processing speed, attention and executive function (SDMT, Stroop and TMT battery GREFEX, and divided attention substests (TAP) and 1 score \<1DS on other tests assessing information processing speed, and executive and attention functions (IPS / FAE) and working memory (WM).
• healthy volunteers
• male or female,
• age 18-55 matched for age, gender and education
• Accepting to participate and signing the informed consent
• affiliated to french social security

You may not qualify if:

• existing other neurological or psychiatric disorder, visual, oculomotor, auditory and motor impairments precluding ability to perform computerized tasks and the driving simulator tasks,
• prior history of addictive behaviour,
• MS attack in the 2 months preceding the screening,
• corticosteroid pulse therapy within 2 months preceding screening,
• severe cognitive deficits or dementia (MMS\<27), moderate to severe visuospatial incapacity (type IV or V at the Rey figure score \< 28), moderate to severe depression (BDI \>27),
• Participant without driving licence

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Merck Serono International SA: collaborator
• ARSEP foundation: collaborator

Study Sites (1)

Service de Neurologie - Pôle des Neurosciences Cliniques, CHU de Bordeaux.

Bordeaux, 3300, France

Location

Related Publications (1)

• Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Coupe P, Ouallet JC, Planche V, Moscufo N, Meier DS, Tourdias T, Guttmann CR, Dousset V, Brochet B. Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):146-151. doi: 10.1136/jnnp-2016-313867. Epub 2016 Oct 27.

  PMID: 27789541 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bruno Brochet, Md PhD

  University Hospital, Bordeaux

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 23, 2010
• Study Start: May 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: February 1, 2016
• Last Updated: February 9, 2016

Record last verified: 2016-02

Locations

FR (1)