Cognitive Rehabilitation of Working Memory After Moderate to Severe Traumatic Brain Injury

Study Overview
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Brief Summary
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The study aims to demonstrate improvement of daily life functioning and improvement of cognitive tests in post traumatic brain injury (TBI) patients suffering from working memory deficit, by a 3-month specific cognitive rehabilitation program, in comparison with patients with usual non-specific rehabilitation of same duration. As secondary objectives, the study aims to: demonstrate improvement of specific neuropsychological tests of working memory; demonstrate improvement of non-specific tasks involving working memory; assess the evolution in not-targeted domains by the specific rehabilitation, which would give evidence of a global cognitive stimulation effect; demonstrate improvement of social integration ability and quality of life; demonstrate persistence of effects at 3 months and 6 months after the end of treatment; demonstrate the acceptability, the tolerance and the feasibility of rehabilitation.

Detailed Description
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Working memory is an essential cognitive function which allows to store briefly and treat simultaneous informations, but is often altered after a moderate to severe TBI. This alteration results in disabilities and social integration difficulties in the post TBI patients. The study team had developped a standardized and hierarchized rehabilitation program of working memory. Several experiments have shown the efficacy of the program which is now used in routine care by speech-language pathologists and neuropsychologists. However it is necessary to provide a robust demonstration of its efficacy in improving function in daily life. This randomized multicenter study will be performed in 6 centers in the area of Île-de-France. 54 patients will be randomized 1:1 to receive either specific rehabilitation of working memory or non-specific rehabilitation. A 10-month follow-up is planned for patients of the two arms.

Official Title
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A Randomized Controlled Trial of Cognitive Rehabilitation of Working Memory After Moderate to Severe Traumatic Brain Injury

Conditions
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Moderate to Severe Traumatic Brain Injury

Intervention / Treatment
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* Other: Specific rehabilitation
* Other: Non-specific rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 - 65 years; Moderate to severe TBI (Glasgow score between 3 and 12 in the 24 first hours); At least 6 months following TBI; Complaint related to working memory in daily life (scale > 29 of questionnaire of complaint on working memory (WMQ), and established deficit of working memory by one of the following criteria: Index of working memory (IWM) of Wechsler Adult Intelligence Scale (WAIS-IV) < 85 or p < .05 between IWM and one of the WAIS-IV index; Less than 70% correct responses on Brown-Peterson tasks test in the verbal modality with an interfering task as mental calculation; Less than 89% correct responses on Brown-Peterson tasks test in the verbal modality with an interfering task of articulatory suppression; Less than 70% correct responses on Brown-Peterson tasks test in the visuospatial modality with an interfering motor task. Prior medical examination; Correct vision after visual acuity correction; Stable neurological or psychoactive treatment for at least 4 weeks, if applicable; Able to move to the center where rehabilitation will be performed; Covered by a health insurance; Signed consent of patient or of the guardian. Exclusion Criteria: History of central nervous system disorder, or history of psychological disorder or substance abuse; Prior specific cognitive rehabilitation of working memory; Instrumental activities disabilities, cognitive disorder, behavioural disorders or major psychiatric disorder; Major anxio-depressive syndrome or present psychiatric disorder which can interfere with experimental procedure or measured variables; Pregnant or breastfeeding woman.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single blind trial with 2 parallel arms: Specific rehabilitation of working memory vs. non-specific rehabilitation
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Specific rehabilitation of working memory<br>Specific rehabilitation of working memory according to hierarchized rehabilitation. | Other: Specific rehabilitation<br>* Experimental rehabilitation of working memory: 3 sessions per week during 3 months, for a total 36 sessions.<br>|
| Active Comparator: Control group<br>Non-specific rehabilitation of working memory, usual therapy. | Other: Non-specific rehabilitation<br>* Usual non-specific rehabilitation treatment for moderate to severe TBI in healthcare facilities: 2-3 sessions per week for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of simultaneous responders | A patient will be considered as a responder if he improves simultaneously on the Working Memory Questionnaire (WMQ) and the Brown-Peterson Task. Proportions will be calculated of patients simultaneously improving on the Working Memory Questionnaire (WMQ) and the Brown-Peterson Task: increase of at least 12 points on WMQ scale, at least 13% score improvement on the verbal or visuo-spatial Brown-Peterson Task. | 3 months after the first rehabilitation session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working Memory Questionnaire during rehabilitation program | The Working Memory Questionnaire (WMQ), an auto-questionnaire elaborated by the study team, will be used. The WMQ is a self-administered scale, addressing three dimensions of working memory: short-term storage, attention, and executive control. It is a self-assessment questionnaire comprising 30 questions scored on a five-point Likert scale, ranging from 0 (no problem at all) to 4 (very severe problem in everyday life). The total score will be used. | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | Working memory span tasks | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | Verbal and visuospatial working memory. | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | n-back task | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | Brown-Peterson Visual. | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | reading span task. | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | Working Memory Index (WISC-IV). | At baseline, 3 months, 6 months and 9 months | 
| Cognitive task of working memory | divided attention task | At baseline, 3 months, 6 months and 9 months | 
| Arithmetic resolution | Non-specific tasks involving working memory: arithmetic resolution ability by WAIS index | At baseline, 3 months and 6 months | 
| Non-targeted cognitive measurements | Executive functions will be assessed. | At baseline, 3 months and 6 months | 
| Non-targeted cognitive measurements | Long-term memory will be assessed. | At baseline, 3 months and 6 months | 
| Non-targeted cognitive measurements | The speed of treatment will be assessed. | At baseline, 3 months and 6 months | 
| Social functioning assessement | Assessed by Manual for Sydney Psychosocial Reintegration Scale (SPRS) | At baseline, 3 months, 6 months and 9 months | 
| Quality of life assessment | Assessed by Qolibri scale | At baseline, 3 months, 6 months and 9 months | 
| Quality of life assessment | Assessed by EQ5D-5 | At baseline, 3 months, 6 months and 9 months | 
| Acceptability | Compliance of rehabilitation program: duration of training of speech-language pathologist and psychologist to the rehabilitation program. | At baseline, 3 months and 6 months | 
| Acceptability | Compliance of rehabilitation program: duration of session. | At baseline, 3 months and 6 months | 
| Acceptability | Compliance of rehabilitation program: patient's satisfaction of care (Client Satisfaction Questionnaire (CSQ-8)). | At baseline, 3 months and 6 months | 
| Acceptability | Compliance of rehabilitation program: presence during rehabilitation session of working memory. | At baseline, 3 months and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate to severe traumatic brain injury, cognitive rehabilitation, working memory, daily life function, Working Memory Questionnaire, WMQ, Brown-Peterson test