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

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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Other: Computerized Plasticity-based Adaptive Cognitive Training; Other: Commercially available computerized training

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94108
      • Posit Science Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be 18 - 50 years of age at the time of consent
2. Subjects must have a diagnosis of mTBI
3. 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).
4. 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.
5. Subjects must be fluent English speakers.
6. Subjects must have adequate sensorimotor capacity to perform the program in the judgment of the consenting clinician.

Exclusion Criteria:

1. Subjects must not have a history of penetrating head wounds or a diagnosis of moderate or severe TBI.
2. Subjects must not be in-patients.
3. Subjects must not have a diagnosis of an illness or condition with known cognitive consequences (e.g., schizophrenia, bipolar disorder, cancer, multiple sclerosis).
4. Subjects must not show suicidal ideation as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS).
5. Subjects must now show signs of intoxication due to current substance abuse (including alcohol and/or illegal drugs) during any in person visit.
6. Subjects must not have clinically significant visual field deficits noted by the consenting staff member by direct observation or by medical history.
7. Subjects must not be judged to be lacking effort.
8. Subjects must not have problems performing assessments or comprehending or following spoken instructions.
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Posit Science Corporation
• Collaborators: VA Connecticut Healthcare System; Walter Reed National Military Medical Center; Michael E. DeBakey VA Medical Center; Congressionally Directed Medical Research Programs; VA Boston Healthcare System; Tripler Army Medical Center
• Investigators: Study Director: Cate N Stasio, BA, Posit Science Corporation

Publications and helpful links

General Publications

• Consensus conference. Rehabilitation of persons with traumatic brain injury. NIH Consensus Development Panel on Rehabilitation of Persons With Traumatic Brain Injury. JAMA. 1999 Sep 8;282(10):974-83.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): March 2, 2017
• Study Completion (Actual): March 2, 2017

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 13, 2012

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 11, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: mild Traumatic Brain Injury; computer; Cognitive remediation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: BPI-1002-11