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Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis (REACTIV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01207856
Recruitment Status : Completed
First Posted : September 23, 2010
Last Update Posted : February 9, 2016
Sponsor:
Collaborators:
Merck Serono International SA
ARSEP foundation
Information provided by (Responsible Party):
University Hospital, Bordeaux

Tracking Information
First Submitted Date  ICMJE September 22, 2010
First Posted Date  ICMJE September 23, 2010
Last Update Posted Date February 9, 2016
Study Start Date  ICMJE May 2011
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
Comparison between groups concerning the z cognitive global executive z score . [ Time Frame: after 4 months (M4) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
  • Comparison of brain activation in the treated group versus control group at the fourth condition. [ Time Frame: 4 and 8 months ]
  • Comparison between groups concerning the z score of the SDMT [ Time Frame: 4 and 8 months ]
  • Comparison between groups of the daily-life cognitive questionnaire scores [ Time Frame: at M4 and M8 ]
  • Comparison between groups concerning the z cognitive global executive z score [ Time Frame: 8 months ]
  • Clinical Global impression of patients [ Time Frame: 4 and 8 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis
Official Title  ICMJE Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis and Assessment by Neuroimaging
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.

Detailed Description : Multiple Sclerosis (MS) is the most frequent disabling neurological disease in young adults. Over the past two decades, cognitive impairment in MS has received increasing interest. Although for a long time described in MS text books, it has been underestimated until recently. It is now accepted as an important feature of MS with a high impact on working and social abilities. The cognitive disorders in MS are dominated by a slowdown in information processing speed (IPS), as well as disturbances of attention and memory. The nature of cognitive findings suggest that the impairments depend on the integrity of large-scale cortical integrative processes, which involve long-distance white matter projections which can be impaired due to diffuse demyelinating injury in patients with MS. At the early stages of MS there is increasing evidence that neuroplasticity, the ability of the brain to respond to various insults, allows adaptive reorganization of cognitive functions to limit impairment, despite widespread tissue damage. Recently, we showed that at the early stages of RRMS compensatory capacities are relatively maintained, especially in highly-educated patients suggesting that cognitive training might be useful. The requirement of cerebral compensatory mechanisms to perform the cognitive tests was postulated in MS patients on the basis of functional MRI (fMRI) studies. By using a go/no go task of increasing complexity in a fMRI study in RRMS patients, we observed that a limitation of this compensatory cerebral recruitment appears when the attentional solicitations reach a particular level of difficulty. We postulate that a cognitive training program may help to maintain these compensatory capacities. Therefore, we propose to evaluate the effect of the program on brain activation using a task with several levels of attention requirement (increased attention load) by using fMRI and to evaluate in parallel its clinical effect and its impact in daily activities.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Sclerosis
  • Cognitive Rehabilitation
Intervention  ICMJE
  • Behavioral: specific cognitive rehabilitation
    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).
  • Behavioral: non specific cognitive rehabilitation
    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
  • Other: no intervention
    no intervention
Study Arms  ICMJE
  • Active Comparator: group A
    specific cognitive rehabilitation
    Intervention: Behavioral: specific cognitive rehabilitation
  • Active Comparator: Groupe B : non specific rehabilitation
    Intervention: Behavioral: non specific cognitive rehabilitation
  • group C
    group C for MRI, neuropsychological and ecological assessments
    Intervention: Other: no intervention
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2016)
65
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2010)
75
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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,

Patients will be eligible for randomization (cognitive inclusion criterion) if they performed worse than :

  • 2 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).

or

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01207856
Other Study ID Numbers  ICMJE CHUBX 2010/07
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Hospital, Bordeaux
Original Responsible Party Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
Current Study Sponsor  ICMJE University Hospital, Bordeaux
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Merck Serono International SA
  • ARSEP foundation
Investigators  ICMJE
Study Director: Bruno Brochet, Md PhD UH Bordeaux
PRS Account University Hospital, Bordeaux
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP