TBI (Traumatic Brain Injury)
Conditions
Brief summary
Childhood traumatic brain injury (TBI) poses significant impairment in children's executive functions (EFs) for moderate to severe injuries, yet interventions specifically designed for children's EF rehabilitation post-TBI and rigorous clinical trials to establish the efficacy of such interventions remain unavailable. In this study, the investigators will conduct a randomized clinical trial to evaluate the efficacy of a novel virtual reality (VR)-based training program for EF rehabilitation for childhood TBI.
Detailed description
Traumatic brain injury (TBI) is a leading cause of acquired disability in U.S. children, with an estimated 700,000 cases every year, presenting in 75% of children with trauma and accounting for 70% of deaths from childhood trauma. Childhood TBIs often result in significant impairment in cognitive functions,1 particularly in core executive functions (EFs) due to the vulnerability of the frontal lobes, especially after a moderate to severe TBI. Core EF is composed of three skills: inhibitory control, working memory, and cognitive flexibility. These skills are associated with impaired EF behaviors, increased attention problems, and lower health-related quality-of-life (HRQOL). However, evidence-based EF rehabilitation programs are lacking. Although a combination of diverse cognitive interventions may improve children's EF, limited affordability, accessibility, adherence, and generalizability hamper clinically adapting and implementing such interventions in the rehabilitation setting. Virtual reality (VR) offers an exciting alternative strategy for EF rehabilitation of childhood TBI due to its flexibility, accessibility, and immersive experiences in three dimensions. These properties may increase adherence to training and foster an enhanced transfer of learned EF skills to untrained tasks in everyday life. Thus far, rigor-ous randomized clinical trials (RCTs) have not been conducted to establish the efficacy of VR-based EF reha-bilitation for childhood TBI. The overall goal of the project is to assess the efficacy of a novel VR-based interactive cognitive training (VICT) program for EF rehabilitation in children with TBI with the following aims: Aim 1. Examine VICT's efficacy in improving core and daily EF skills among children with TBI. Hypothesis 1.1: Children in the intervention group will show enhanced improvement over controls in trained VR-based EF tasks and untrained NIH Toolbox tasks from baseline to post-intervention and follow-up visits; Hypothesis 1.2: The intervention group will show better reported daily EF than controls at the follow-up visit; Hypothesis 1.3: Children in the intervention group will show faster improvement than controls in daily-reported EF skills between post-intervention and follow-up visits. Aim 2. Examine VICT's efficacy in reducing attentional problems among children with TBI. Hypothesis 2.1: Children in the intervention group will show a greater reduction in attentional problems as measured by testing on the Conners Continuous Performance Test 3rd Edition™ (Conners CPT 3TM) from baseline to the post-intervention and follow-up visits than controls; Hypothesis 2.2: Children in the intervention group will show fewer everyday attentional problems on the Be-havior Assessment System for Children 3rd Ed (BASC-3) self- and parent-ratings of attention at the follow-up visit than controls; Hypothesis 2.3: The direct effect of the VICT program in reducing attention problems will be mediated by children's EF behaviors as measured by the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) at the follow-up visit. Aim 3. Examine VICT's efficacy in improving HRQOL among children with TBI. Hypothesis 3.1: The intervention group will show higher levels of reported HRQOL than controls at follow-up; Hypothesis 3.2: The direct effect of the VICT program on HRQOL at follow-up will be mediated by children's EF skills and ratings of EF behaviors and attention at the post-intervention and follow-up visits.
Interventions
Three virtual reality-based games designed to train inhibitory control, working memory, and cognitive flexibility among children with TBI
A virtual playground for control group to interact without training executive functions
Sponsors
Study design
Eligibility
Inclusion criteria
1. diagnosed with TBI within the past 12 months and under 18 years at the time of injury; 2. fluent in English; and 3) Score \<28 on the Agitated Behavior Scale (if available).
Exclusion criteria
1. comorbidities or premorbid disorders that prevent proper administration of VR and study measures, 2. restriction from using electronic devices, 3. post-injury seizure activity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VR-based EF Assessment Task | Baseline (at recruitment/before intervention), Post-Intervention (after completion of intervention, up to 2 weeks), Follow-Up (up to 6 months after completion of intervention) | Performance-based executive function assessment Task in the virtual reality environment built by the research team. There are three tasks within this measurement, each transformed into a z score and summed up to serve as the total score for this measure. A Z-score of 0 in each task represents the sample mean. Higher values represent a better outcome for this measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Report-based EF Skills | Follow-Up (up to 6 months after completion of intervention) | Behavior Rating Inventory of Executive Function 2; T scores are used (M = 50, SD = 10, no lower/upper limit), T scores from 60 to 64 are considered mildly elevated, and T scores from 65 to 69 are considered potentially clinically elevated. T scores at or above 70 are considered clinically elevated |
| Health-related Quality of Life | Follow-Up (up to 6 months after completion of intervention) | 23-item PedsQL (Pediatric Quality of Life) Generic Core Scales were designed to measure the core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. The current study uses its total scores, which is the sum of all 23 items and ranges from 0-100 after transformation. Higher scores indicate better quality of life. |
| NIH Toolbox Cognition Battery | Baseline (at recruitment/before intervention), Post-Intervention (after completion of intervention, up to 2 weeks), Follow-Up (up to 6 months after completion of intervention) | Performance-based executive functions tested by three tasks in the NIH Toolbox Cognition Battery: Dimensional Change Card Sort Test, List Sorting Working Memory Test, and Flanker Inhibitory Control and Attention Test. Scores of each task were computed as age-corrected standard scores automatically by the iPad app of the NIH Toolbox Cognition Battery. Each age-corrected standard score is a z-score with a mean of 100 and standard deviation of 15. Total scores are the mean of all three task age-corrected standard scores. Higher scores represent better outcomes. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Perceived VR Experience | Post-Intervention, up to 2 weeks | VR User Feedback Survey providing subjective feedback on the VR intervention (1-5, higher scores indicate better VR experience) |
| Motion Sickness | Post-Intervention, up to 2 weeks | Simulator Sickness Questionnaire, 0-3, higher scores indicate higher levels of motion sickness |
| Perceived Exertion | Post-Intervention, up to 2 weeks | Borg Perceived Exertion Scale (6-26, higher score indicates greater exertion) |
Countries
United States
Participant flow
Recruitment details
14 participants were recruited during 9/2021 and 8/2024 from two participating sites: Spaulding Rehabilitation Hospital and Kennedy Krieger Institute
Participants by arm
| Arm | Count |
|---|---|
| Virtual Reality Games for Training Executive Functions Virtual Reality games for training three core executive functions | 7 |
| Control VR Game on Playground A relaxing virtual reality game for control group to play in VR playground without training their executive functions | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Virtual Reality Games for Training Executive Functions | Control VR Game on Playground | Total |
|---|---|---|---|
| Age, Continuous | 12.43 Years STANDARD_DEVIATION 1.99 | 13.57 Years STANDARD_DEVIATION 4.2 | 13.00 Years STANDARD_DEVIATION 3.21 |
| Injury Recency | 73.75 Days STANDARD_DEVIATION 25.62 | 129.50 Days STANDARD_DEVIATION 156.64 | 101.62 Days STANDARD_DEVIATION 108.1 |
| Race/Ethnicity, Customized Black | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized More than One Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
| TBI Severity Mild Complicated TBI | 3 Participants | 2 Participants | 5 Participants |
| TBI Severity Moderate/Severe TBI | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 0 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
VR-based EF Assessment Task
Performance-based executive function assessment Task in the virtual reality environment built by the research team. There are three tasks within this measurement, each transformed into a z score and summed up to serve as the total score for this measure. A Z-score of 0 in each task represents the sample mean. Higher values represent a better outcome for this measure.
Time frame: Baseline (at recruitment/before intervention), Post-Intervention (after completion of intervention, up to 2 weeks), Follow-Up (up to 6 months after completion of intervention)
Population: Some participants did not have complete/valid data points for baseline, post, or follow-up visits on this outcome and thus excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | VR-based EF Assessment Task | Post Intervention | 1.41 Z-Score | Standard Deviation 0.77 |
| Virtual Reality Games for Training Executive Functions | VR-based EF Assessment Task | Follow Up | 1.71 Z-Score | Standard Deviation 0.59 |
| Virtual Reality Games for Training Executive Functions | VR-based EF Assessment Task | Pre Intervention | 1.15 Z-Score | Standard Deviation 0.55 |
| Control VR Game on Playground | VR-based EF Assessment Task | Post Intervention | 1.53 Z-Score | Standard Deviation 0.46 |
| Control VR Game on Playground | VR-based EF Assessment Task | Follow Up | 1.82 Z-Score | Standard Deviation 0.06 |
| Control VR Game on Playground | VR-based EF Assessment Task | Pre Intervention | 1.15 Z-Score | Standard Deviation 0.34 |
Health-related Quality of Life
23-item PedsQL (Pediatric Quality of Life) Generic Core Scales were designed to measure the core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. The current study uses its total scores, which is the sum of all 23 items and ranges from 0-100 after transformation. Higher scores indicate better quality of life.
Time frame: Follow-Up (up to 6 months after completion of intervention)
Population: Some participants did not have complete/valid data points for baseline, post, or follow-up visits on this outcome and thus excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | Health-related Quality of Life | Parent Report | 78.88 units on a scale | Standard Deviation 20.89 |
| Virtual Reality Games for Training Executive Functions | Health-related Quality of Life | Child Report | 75.90 units on a scale | Standard Deviation 13.49 |
| Control VR Game on Playground | Health-related Quality of Life | Parent Report | 75.54 units on a scale | Standard Deviation 8.76 |
| Control VR Game on Playground | Health-related Quality of Life | Child Report | 70.67 units on a scale | Standard Deviation 4.64 |
NIH Toolbox Cognition Battery
Performance-based executive functions tested by three tasks in the NIH Toolbox Cognition Battery: Dimensional Change Card Sort Test, List Sorting Working Memory Test, and Flanker Inhibitory Control and Attention Test. Scores of each task were computed as age-corrected standard scores automatically by the iPad app of the NIH Toolbox Cognition Battery. Each age-corrected standard score is a z-score with a mean of 100 and standard deviation of 15. Total scores are the mean of all three task age-corrected standard scores. Higher scores represent better outcomes.
Time frame: Baseline (at recruitment/before intervention), Post-Intervention (after completion of intervention, up to 2 weeks), Follow-Up (up to 6 months after completion of intervention)
Population: Some participants did not have complete/valid data points for baseline, post, or follow-up visits on this outcome and thus excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | NIH Toolbox Cognition Battery | Post Intervention | 91.11 Z-score | Standard Deviation 11.83 |
| Virtual Reality Games for Training Executive Functions | NIH Toolbox Cognition Battery | Follow Up | 90.87 Z-score | Standard Deviation 11.25 |
| Virtual Reality Games for Training Executive Functions | NIH Toolbox Cognition Battery | Pre Intervention | 87.67 Z-score | Standard Deviation 10.26 |
| Control VR Game on Playground | NIH Toolbox Cognition Battery | Post Intervention | 90.87 Z-score | Standard Deviation 11.25 |
| Control VR Game on Playground | NIH Toolbox Cognition Battery | Follow Up | 88.83 Z-score | Standard Deviation 20.06 |
| Control VR Game on Playground | NIH Toolbox Cognition Battery | Pre Intervention | 83.56 Z-score | Standard Deviation 12.59 |
Report-based EF Skills
Behavior Rating Inventory of Executive Function 2; T scores are used (M = 50, SD = 10, no lower/upper limit), T scores from 60 to 64 are considered mildly elevated, and T scores from 65 to 69 are considered potentially clinically elevated. T scores at or above 70 are considered clinically elevated
Time frame: Follow-Up (up to 6 months after completion of intervention)
Population: Some participants did not have complete/valid data points for baseline, post, or follow-up visits on this outcome and thus excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | Report-based EF Skills | Parent Report | 52.00 Points | Standard Deviation 6.82 |
| Virtual Reality Games for Training Executive Functions | Report-based EF Skills | Child Report | 51.75 Points | Standard Deviation 12.42 |
| Control VR Game on Playground | Report-based EF Skills | Parent Report | 50.25 Points | Standard Deviation 8.81 |
| Control VR Game on Playground | Report-based EF Skills | Child Report | 49.67 Points | Standard Deviation 4.51 |
Motion Sickness
Simulator Sickness Questionnaire, 0-3, higher scores indicate higher levels of motion sickness
Time frame: Post-Intervention, up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | Motion Sickness | 0.09 Points | Standard Deviation 0.13 |
| Control VR Game on Playground | Motion Sickness | 0.24 Points | Standard Deviation 0.26 |
Perceived Exertion
Borg Perceived Exertion Scale (6-26, higher score indicates greater exertion)
Time frame: Post-Intervention, up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | Perceived Exertion | 7.38 Points | Standard Deviation 1.24 |
| Control VR Game on Playground | Perceived Exertion | 9.71 Points | Standard Deviation 5.06 |
Perceived VR Experience
VR User Feedback Survey providing subjective feedback on the VR intervention (1-5, higher scores indicate better VR experience)
Time frame: Post-Intervention, up to 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | VR Quality | 2.50 Points | Standard Deviation 1.05 |
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | Pleasure | 3.25 Points | Standard Deviation 1.33 |
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | motivation-Like to use VR again | 3.17 Points | Standard Deviation 0.93 |
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | motivation-use VR in future | 2.83 Points | Standard Deviation 1.37 |
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | motivation-use VR in therapies | 3.42 Points | Standard Deviation 1.56 |
| Virtual Reality Games for Training Executive Functions | Perceived VR Experience | motivation-attend | 3.08 Points | Standard Deviation 1.5 |
| Control VR Game on Playground | Perceived VR Experience | motivation-use VR in therapies | 3.50 Points | Standard Deviation 1.52 |
| Control VR Game on Playground | Perceived VR Experience | VR Quality | 3.08 Points | Standard Deviation 1.28 |
| Control VR Game on Playground | Perceived VR Experience | motivation-use VR in future | 3.37 Points | Standard Deviation 1.21 |
| Control VR Game on Playground | Perceived VR Experience | Pleasure | 3.92 Points | Standard Deviation 1.02 |
| Control VR Game on Playground | Perceived VR Experience | motivation-attend | 3.00 Points | Standard Deviation 1.67 |
| Control VR Game on Playground | Perceived VR Experience | motivation-Like to use VR again | 3.92 Points | Standard Deviation 1.2 |