Broad-spectrum Cognitive Remediation: Effects of a Brain Plasticity-based Program in Mild Traumatic Brain Injury

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effects of plasticity-based, adaptive cognitive remediation on the cognitive abilities, functional status and quality of life of soldiers and veterans diagnosed with persistent post-concussive symptoms (PPCS) following a mild traumatic brain injury (mTBI, also referred to as a concussion, or blast exposure), as compared to a computer-based control.

Detailed Description
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This study is a multi-site, prospective, parallel arm, double-blind, randomized, controlled clinical trial to assess the safety and efficacy of plasticity-based, adaptive, computerized cognitive remediation treatment versus a computer-based control. Both the study and the cognitive remediation treatments meet the criteria of Non-Significant Risk.

Official Title
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BRAVE Trial: Broad-spectrum Cognitive Remediation Available to Veterans: Effects of a Brain Plasticity-based Program in Mild Traumatic Brain Injury (mTBI)

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Other: Computerized Plasticity-based Adaptive Cognitive Training
* Other: Commercially available computerized training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be 18 - 50 years of age at the time of consent Subjects must have a diagnosis of mTBI Subjects must have persistent cognitive dysfunction confirmed by an objective measure (as recommended by the ICD-10 definition for post-concussion syndrome) or a subjective measure (as recommended by the DSV-IV definition of post-concussional disorder). Subjects must be at least three months out from their most recent TBI, concussion, and/or blast exposure to minimize the effects of spontaneous recovery, as verified through participant interview. Subjects must be fluent English speakers. Subjects must have adequate sensorimotor capacity to perform the program in the judgment of the consenting clinician. Exclusion Criteria: Subjects must not have a history of penetrating head wounds or a diagnosis of moderate or severe TBI. Subjects must not be in-patients. Subjects must not have a diagnosis of an illness or condition with known cognitive consequences (e.g., schizophrenia, bipolar disorder, cancer, multiple sclerosis). Subjects must not show suicidal ideation as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects must now show signs of intoxication due to current substance abuse (including alcohol and/or illegal drugs) during any in person visit. Subjects must not have clinically significant visual field deficits noted by the consenting staff member by direct observation or by medical history. Subjects must not be judged to be lacking effort. Subjects must not have problems performing assessments or comprehending or following spoken instructions. Subjects must not be enrolled in a concurrent clinical trial involving an investigational pharmaceutical, nutraceutical, medical device, or behavioral treatment for TBI that could affect the outcome of this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Treatment<br>Computerized plasticity-based adaptive cognitive training, up to 65 hours | Other: Computerized Plasticity-based Adaptive Cognitive Training<br>* Computerized plasticity-based adaptive cognitive training, up to 65 hours<br>|
| Active Comparator: Active Comparator<br>Commercially available computerized training, up to 65 hours | Other: Commercially available computerized training<br>* Commercially available computerized training, up to 65 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Function | Between-group magnitude of change in composite score with the measure constructed from Rey Auditory Verbal Learning Test (RAVLT) sum of trials 1-5 (immediate verbal memory), RAVLT delayed verbal recall, the Ruff Light Trails Test (RULIT) sum of trials 2-10 (immediate visual memory), RULIT delayed recall scores, digit span (WAIS, sum of forwards, backwards, sequencing), symbol span (WMS), anti-saccades, flanker, and set-shifting (each from the EXAMINER battery). | After three months of training | 
| Change in Functional Performance | Between-group magnitude of change in sum time of all tasks in the Timed Instrumental Activities of Daily Living (TIADL). Higher scores indicate greater impairment in functional performance. | After three months of training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mental Health-Related Quality of Life | Between-group magnitude of change in the Mental Component Score (MCS) as measured by the SF-12v2 Health Survey. The component score is a normed-based score with a mean of 50. Scores less than 50 indicate worse mental health than the mean. | After three months of training and 3 months after training completion | 
| Change in Physical Health-Related Quality of Life | Between-group magnitude of change in the Physical Component Score (PCS) as measured by the SF-12v2 Health Survey. The component score is a normed-based score with a mean of 50. Scores less than 50 indicate worse physical health than the mean. | After three months of training and 3 months after training completion | 
| Change in Depressive Symptoms | Between-group magnitude of change in sum score using the self-report measure, Beck Depression Inventory (BDI-II). The scoring range is 0-63. Higher scores indicate more severe depressive symptoms. | After three months of training and 3 months after training completion | 
| Change in PTSD Symptoms | Between-group magnitude of change in sum score using the self-report measure, PTSD Checklist - Civilian Version (PCL-C). The scoring range is 17-85. Higher scores indicate more severe PTSD symptoms. | After three months of training and 3 months after training completion | 
| Change in Executive Function Symptoms | Between-group magnitude of change in After total T-score using the self-report measure, Frontal Systems Behavior Scale (FrSBe). Raw scores are converted to age- and education-corrected T-scores. The mean T-score is 50, scores greater than 65 are considered clinically significant. | After three months of training and 3 months after training completion | 
| Change in Cognitive Symptoms | Between-group magnitude of change in sum score using the self-report measure, Cognitive Failures Questionnaire (CFQ). The scoring range is 0-100. Higher scores indicate more severe cognitive symptoms. | After three months of training and 3 months after training completion | 
| Change in Neurobehavioral Symptoms | Between-group magnitude of change in sum score using the self-report measure, Neurobehavioral Symptoms Index (NSI). The scoring range is 0-88. Higher scores indicate more severe neurobehavioral symptoms. | After three months of training and 3 months after training completion | 
| Change in TBI Functional Status | Between-group magnitude of change in overall T-score using the self-report measure, Mayo-Portland Adaptability Inventory (MPAI-4). The overall T-score range is -38 to 106. Higher scores indicate more severe TBI functional status. | After three months of training and 3 months after training completion | 
| Change in Immediate Verbal Memory | Between-group magnitude of change in sum of Trials 1-5 of the Rey Auditory Verbal Learning Test (RAVLT). The scoring range is 0-75. Lower scores indicate greater impairment in immediate verbal memory. | After three months of training and 3 months after training completion | 
| Change in Delayed Verbal Memory | Between-group magnitude of change in total score of delayed verbal recall on the Rey Auditory Verbal Learning Test (RAVLT). The scoring range is 0-15. Lower scores indicate greater impairment in delayed verbal memory. | After three months of training and 3 months after training completion | 
| Change in Immediate Visual Memory | Between-group magnitude of change in sum of Trials 2-10 of the Ruff Light Trails Test (RULIT). The scoring range is 0-135. Lower scores indicate greater impairment in immediate visual memory. | After three months of training and 3 months after training completion | 
| Change in Delayed Visual Memory | Between-group magnitude of change in total score of delayed visual recall on the Ruff Light Trails Test (RULIT). The scoring range is 0-15. Lower scores indicate greater impairment in delayed visual memory. | After three months of training and 3 months after training completion | 
| Change in Short-Term Verbal Memory Span | Between-group magnitude of change in sum of forwards, backwards, and sequencing tasks of the Wechsler Adult Intelligence Scale (WAIS) 4th Edition - Digit Span. The scoring range is 0-48. Lower scores indicate greater impairment in short-term verbal memory. | After three months of training and 3 months after training completion | 
| Change in Short-Term Visual Memory Span | Between-group magnitude of change in total score of the Wechsler Memory Scale (WMS) 4th Edition - Symbol Span. The scoring range is 0-50. Lower scores indicate greater impairment in short-term visual memory. | After three months of training and 3 months after training completion | 
| Change in Inhibition of Reflexive Saccade | Between-group magnitude of change in total score of the Anti-Saccade task of the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER). The scoring range is 0-40. Lower scores indicate greater impairment in reflexive saccade inhibition. | After three months of training and 3 months after training completion | 
| Change in Response Inhibition | Between-group magnitude of change in total score of the Flanker task of the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER). The scoring range is 0-10. Lower scores indicate greater impairment in response inhibition. | After three months of training and 3 months after training completion | 
| Change in Cognitive Flexibility | Between-group magnitude of change in total score of the Set-Shifting task of the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER). The scoring range is 0-10. Lower scores indicate greater impairment in mental flexibility. | After three months of training and 3 months after training completion | 
| Change in Functional Performance | Between-group magnitude of change in sum score of all tasks in the Timed Instrumental Activities of Daily Living (TIADL). Higher scores indicate greater impairment in functional performance. | 3 months after training completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild Traumatic Brain Injury, Cognitive remediation, computer