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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Bordeaux
Sponsor:
Collaborators:
Merck Serono International SA
ARSEP foundation
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01207856
First received: September 22, 2010
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Multiple Sclerosis
Cognitive Rehabilitation
Behavioral: specific cognitive rehabilitation
Behavioral: non specific cognitive rehabilitation
Other: no intervention

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis and Assessment by Neuroimaging

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Comparison between groups concerning the z cognitive global executive z score . [ Time Frame: after 4 months (M4) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of brain activation in the treated group versus control group at the fourth condition. [ Time Frame: 4 and 8 months ] [ Designated as safety issue: No ]
  • Comparison between groups concerning the z score of the SDMT [ Time Frame: 4 and 8 months ] [ Designated as safety issue: No ]
  • Comparison between groups of the daily-life cognitive questionnaire scores [ Time Frame: at M4 and M8 ] [ Designated as safety issue: No ]
  • Comparison between groups concerning the z cognitive global executive z score [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Clinical Global impression of patients [ Time Frame: 4 and 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: May 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: group A
specific cognitive rehabilitation
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).
Active Comparator: Groupe B : non specific rehabilitation 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
group C
group C for MRI, neuropsychological and ecological assessments
Other: no intervention
no intervention

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207856

Contacts
Contact: Bruno BROCHET, MD PhD 05 56 79 55 21 bruno.brochet@chu-bordeaux.fr
Contact: Mathilde DELOIRE, PhD mathilde.grassin@bb-luni.u-bordeaux2.fr

Locations
France
Service de Neurologie - Pôle des Neurosciences Cliniques, CHU de Bordeaux. Recruiting
Bordeaux, France, 3300
Contact: Bruno BROCHET, Pr    +33 (0)5 56 79 55 21    bruno.brochet@chu-bordeaux.fr   
Contact: Mathilde Deloire-Grassin    + 33(0)5 57 57 57 48 17    mathilde.grassin@bb-luni.u-bordeaux2.fr   
Principal Investigator: Bruno Mrochet, Pr         
Sponsors and Collaborators
University Hospital, Bordeaux
Merck Serono International SA
ARSEP foundation
Investigators
Study Director: Bruno Brochet, Md PhD UH Bordeaux
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01207856     History of Changes
Other Study ID Numbers: CHUBX 2010/07
Study First Received: September 22, 2010
Last Updated: July 1, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Multiple sclerosis
functional MRI
cognitive rehabilitation
ecological evaluation
neuroplasticity

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 26, 2014