Multiple SclerosisREACTIVNCT01207856
Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis
A study testing specific cognitive rehabilitation and non specific cognitive rehabilitation in people with Multiple Sclerosis and Cognitive Rehabilitation, run by University Hospital, Bordeaux at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Cognitive Rehabilitation
- What is being tested?
- specific cognitive rehabilitation and non specific cognitive rehabilitation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteFrance
- Study dates
- May 2011to Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Neurologie - Pôle des Neurosciences Cliniques, CHU de Bordeaux.
Bordeaux, 3300
About this study
Official title: Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis and Assessment by Neuroimaging
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.
Read more
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.
Read the 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.
- Conditions
- Multiple Sclerosis, Cognitive Rehabilitation
- Being tested
- specific cognitive rehabilitation, non specific cognitive rehabilitation, no intervention
- Keywords
- Multiple sclerosis, functional MRI, cognitive rehabilitation, ecological evaluation, neuroplasticity
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
specific cognitive rehabilitationBehavioural
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).
non specific cognitive rehabilitationBehavioural
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
no interventionOther
no intervention
| Study group | Role | What they receive |
|---|---|---|
| group A | Active comparator | specific cognitive rehabilitation Receives: Behavioral: specific cognitive rehabilitation |
| Groupe B : non specific rehabilitation | Active comparator | Not described Receives: Behavioral: non specific cognitive rehabilitation |
| group C | Other | group C for MRI, neuropsychological and ecological assessments Receives: Other: no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison between groups concerning the z cognitive global executive z score .
Measured: after 4 months (M4)
Secondary outcomes (5)
Comparison of brain activation in the treated group versus control group at the fourth condition.
Measured: 4 and 8 months
Comparison between groups concerning the z score of the SDMT
Measured: 4 and 8 months
Comparison between groups of the daily-life cognitive questionnaire scores
Measured: at M4 and M8
Comparison between groups concerning the z cognitive global executive z score
Measured: 8 months
Clinical Global impression of patients
Measured: 4 and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2010 (estimated)
- Study startMay 2011
- Primary completionJul 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Serono International SA, ARSEP foundation
- Responsible party
- Sponsor
- Investigators
- Bruno Brochet, Md PhD, Study director, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01207856
- Sponsor's protocol ID
- CHUBX 2010/07
- Acronym
- REACTIV
- Status last verified
- Feb 2016
- First submitted
- 22 Sep 2010
- Last updated
- 9 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 27789541
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis and Assessment by Neuroimaging
- ClinicalTrials.gov ID
- NCT01207856
- Acronym / sponsor ID
- REACTIV / CHUBX 2010/07
- Conditions
- Multiple Sclerosis, Cognitive Rehabilitation
- Keywords
- Multiple sclerosis, functional MRI, cognitive rehabilitation, ecological evaluation, neuroplasticity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- Merck Serono International SA, ARSEP foundation
- Study start
- May 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 23 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| group A | Active comparator | Behavioral: specific cognitive rehabilitationspecific cognitive rehabilitation |
| Groupe B : non specific rehabilitation | Active comparator | Behavioral: non specific cognitive rehabilitation |
| group C | Other | Other: no interventiongroup C for MRI, neuropsychological and ecological assessments |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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 :
Key exclusion criteria (6 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| specific cognitive rehabilitationIndividual 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). | Behavioural | group A |
| non specific cognitive rehabilitationA 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 | Behavioural | Groupe B : non specific rehabilitation |
| no interventionno intervention | Other | group C |
Primary outcome
Comparison between groups concerning the z cognitive global executive z score .
Time frame: after 4 months (M4)
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2016.
- Derived from this study: PubMed 27789541Moroso 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Brochet, Md PhD study director
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing specific cognitive rehabilitation and non specific cognitive rehabilitation in people with Multiple Sclerosis and Cognitive Rehabilitation, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison between groups concerning the z cognitive global executive z score . (time frame: after 4 months (M4)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01207856, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2016.