VR-based EF Rehabilitation for Pediatric TBI

• ClinicalTrials.gov Identifier: NCT03611062
• Recruitment Status: Completed
• First Posted: August 2, 2018
• Last Update Posted: August 20, 2020
• Sponsor: University of Massachusetts, Lowell
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Jiabin Shen, University of Massachusetts, Lowell

Study Description

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 safety and efficacy of such interventions remain unavailable. In this study, the investigators will conduct a small-scale pilot randomized clinical trial to evaluate the safety and preliminary efficacy of a novel virtual reality (VR)-based training program for EF rehabilitation for mild complicated to severe childhood TBI. Knowledge from this research will provide empirical evidence for a larger-scale RCT after the conclusion of this pilot study, with the aim to improve the long-term health and quality of life in children with TBI, as well as promote efficiency and effectiveness of future psychological rehabilitation for children with TBI.

Condition or disease	Intervention/treatment	Phase
Traumatic Brain Injury	Behavioral: VR Executive Functions Training; Behavioral: VR Placebo Game	Not Applicable

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, 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, whose impairment is associated with impaired daily EF skills, increased attention problems, and lower quality-of-life (QoL). The CDC reported to Congress in 2015 that post-TBI cognitive rehabilitation was the No. 1 unmet health care need for children with TBI. However, evidence-based EF rehabilitation programs are lacking. Although research has shown that a combination of diverse cognitive interventions may improve children's EF, clinically adapting and implementing such interventions in the rehabilitation setting is hampered by limited affordability, accessibility, adherence, and generalizability. Virtual reality (VR) offers an exciting alternative strategy for EF rehabilitation of childhood TBI for three reasons. First, VR has the flexibility to offer various EF training activities in a virtual environment within a restricted physical space. Second, VR can be delivered via Internet/mobile platforms, allowing children to participate in post-discharge training at home as needed. Third, unlike traditional computerized training programs, VR can provide immersive experiences in three dimensions. This may increase adherence to training and foster greater transfer of learned EF skills to untrained tasks in everyday life. Thus far, rigorous randomized clinical trials (RCTs) have not been conducted to establish the safety and efficacy of VR-based EF rehabilitation for childhood TBI.

The overall goal of this pilot project is to assess the feasibility, safety, and preliminary efficacy of a novel VR-based interactive cognitive training (VICT) program for EF rehabilitation in children ages 7-17 years with complicated mild to severe TBI. The VICT program is an integrative hardware and software VR system that trains the three core EFs within a challenging animated mission. Using a small parallel-group RCT, the study focuses on refining clinically-appropriate VR research paradigms in pediatric rehabilitation settings and obtaining feasibility, safety, and preliminary efficacy data on children's EF improvement. After the conclusion of the present pilot study, the investigators will utilize the knowledge and skills gained from this phase to conduct a full-scale longitudinal parallel-group RCT to formally evaluate the VICT program's efficacy.

Specifically, a small parallel-group RCT will be carried out in this study. The investigators aim to recruit 20-30 children with complicated mild to severe TBI and randomly assign each participant to either an intervention group (VICT) or a control group (comparable VR game without EF training). Preliminary efficacy outcomes will be assessed at pre-, post-intervention, and a follow-up visit up to six months after the post-intervention assessment.

Aim 1. Refine clinically-appropriate paradigms for VR childhood TBI rehabilitation research.

Aim 2. Explore feasibility, safety and preliminary efficacy of the VICT program. The feasibility and safety of the VICT program will be examined through both quantitative measures (adverse events, simulator sickness, and fatigability) and a semi-structured interview with children, families, and clinicians regarding perceived benefits and challenges. Preliminary efficacy data will be obtained on core EF, daily EF, attention problems, and health-related QoL for both groups. These data will then be used in a conservative way to estimate the effect size of this novel intervention and calculate the required sample size for future RCTs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Other
• Official Title: A Pilot Study on Virtual Reality-based Rehabilitation for Children With Traumatic Brain Injuries
• Actual Study Start Date: August 15, 2018
• Actual Primary Completion Date: August 12, 2020
• Actual Study Completion Date: August 12, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: VR Executive Functions Training; Participants will receive training of executive functions in a virtual reality environment.	Behavioral: VR Executive Functions Training; The Windows 10-based VICT program invites children to rescue an animated character named "Lubdub" from a castle. The program consists of three challenging and child-friendly tasks that correspond to the three core EFs.
Placebo Comparator: Control; Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions.	Behavioral: VR Placebo Game; In this game, children in the control group will use the VR hand controller to cast different types of spells (bees, bouncy balls, sparkler spells) to objects in the virtual world. Objects in the VR world will all react differently to a spell being cast so as to provide children a relaxing and EF-free gaming experience.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Simulator Sickness [Feasibility and Safety] [ Time Frame: Baseline ]
   Measured by the Simulator Sickness Questionnaire. Total scores range from 0 to 26, with 0 representing a better outcome of less sickness.
2. Incidence of Simulator Sickness [Feasibility and Safety] [ Time Frame: Post-Intervention, up to 2 weeks ]
   Measured by the Simulator Sickness Questionnaire. Total scores range from 0 to 26, with 0 representing a better outcome of less sickness.
3. Incidence of Physical Fatigability [Feasibility and Safety] [ Time Frame: Baseline ]
   Measured by the Borg Rating of Perceived Exertion Scale. Total score ranges from 6 to 20, with 6 being a lower amount of exertion.
4. Incidence of Physical Fatigability [Feasibility and Safety] [ Time Frame: Post-Intervention, up to 2 weeks ]
   Measured by the Borg Rating of Perceived Exertion Scale. Total score ranges from 6 to 20, with 6 being a lower amount of exertion.
5. Incidence of Perceived Virtual Reality Experience [Feasibility] [ Time Frame: Baseline ]
   Measured by an open-ended and semi-structured interview of participants, families, and clinicians. Information is collected on subjective experience with the intervention, including level of pleasure, intention of use in future therapies, and perceived benefits/challenges.
6. Incidence of Perceived Virtual Reality Experience [Feasibility] [ Time Frame: Post-Intervention, up to 2 weeks ]
   Measured by an open-ended and semi-structured interview of participants, families, and clinicians. Information is collected on subjective experience with the intervention, including level of pleasure, intention of use in future therapies, and perceived benefits/challenges.
7. Incidence of Treatment-Emergent Adverse or Serious Adverse Events [Safety and Tolerability] [ Time Frame: Through study completion, an average of 2 weeks ]

Secondary Outcome Measures :

1. Performance-based Executive Function Skills in Virtual Reality [ 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) ]
   Measured by Virtual Reality-based Interactive Cognitive Training Assessment Mode. This is a non-standardized assessment of cognitive flexibility, working memory, and inhibitory control.
2. Real-life Executive Function Skills [ Time Frame: Follow-Up (up to 6 months after completion of intervention) ]
   As measured by the parent-report Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2).
3. Real-life Executive Function Skills [ Time Frame: Baseline (at recruitment/before intervention), Post-Intervention (after completion of intervention, up to 2 weeks), Follow-Up (up to 6 months after hospital discharge) ]
   Measured by the self-report TBI-QOL Item Bank v1.0-Executive Function-Short Form 10a
4. Performance-based Attention Problems [ 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) ]
   Measured by Conners Continuous Performance Test 3 (CPT3).
5. Physical, Emotional, and Social Health and School Functioning [Quality of Life] [ Time Frame: Follow-Up (up to 6 months after completion of intervention) ]
   Measured by Parent/Child-reported Pediatric Quality of Life (PedsQL) Generic Core Scales. Scores range from 0 to 100, with higher scores representing better quality of life outcomes.
6. Parent Report-based Attention and Behavior Problems [ Time Frame: Follow-Up (up to 6 months after completion of intervention) ]
   Children's competencies and behavior problems measured by the Child Behavior Checklist (CBCL). It consists of 112 behavioral items (and 1 open-ended item) scored on a 3-step response scale from Not true (0) to Very true or Often true (2). It has 8 subscales and 2 groupings. For the subscales, age- standardized T scores less than 67 are considered in the normal range, T scores ranging from 67-70 are considered to be borderline clinical, and T scores above 70 are in the clinical range. For groupings, T scores less than 60 are considered in the normal range, 60-63 represent borderline scores, and scores greater than 63 are in the clinical range. (Achenbach 1991)
7. Performance-based Executive Function Skills-Inhibitory Control and Attention [ 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 ]
   Measured by the National Institutes of Health Toolbox Cognitive Battery, specifically the Flanker Inhibitory Control and Attention Test for the appropriate age group.
8. Performance-based Executive Function Skills-Working Memory [ 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) ]
   Measured by the National Institutes of Health Toolbox Cognitive Battery, specifically the List Sorting Working Memory Test for the appropriate age group.
9. Performance-based Executive Function Skills-Cognitive Flexibility and Attention [ 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) ]
   Measured by the National Institutes of Health Toolbox Cognitive Battery, specifically the Dimensional Change Card Sort Test for the appropriate age group.

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. diagnosed with TBI
2. between 7 to 17 years old (inclusive)
3. lowest post-resuscitation Glasgow Coma Scale (GCS)=13-15 combined with trauma-related abnormalities on neuroimaging or a depressed skull fracture (complicated mild TBI, CDC/NIH definition), GCS=9-12 (moderate TBI, CDC/NIH definition), and GCS=3-8 (severe TBI, CDC/NIH definition)
4. fluent in English-based communication
5. currently score <28 on the Agitated Behavior Scale (ABS), indicating mild to no agitation.

Exclusion Criteria:

1. severe physical/visual/cognitive comorbidities secondary to TBI that prevent proper utilization of a VR-based game and valid administration of the study measures
2. premorbid neurological disorder or neurodevelopmental issues prior to injury that prevent proper utilization of a VR-based game and valid administration of the study measures
3. patients who are restricted from using electronic gaming devices.

Contacts and Locations

Locations

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Sponsors and Collaborators

University of Massachusetts, Lowell

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  Study Documents (Full-Text)

Documents provided by Jiabin Shen, University of Massachusetts, Lowell:

Study Protocol and Statistical Analysis Plan  [PDF] April 8, 2019

Informed Consent Form  [PDF] April 17, 2019

More Information

• Responsible Party: Jiabin Shen, Principal Investigator, University of Massachusetts, Lowell
• ClinicalTrials.gov Identifier: NCT03611062
• Other Study ID Numbers: IRB18-00472; 1K99HD093814-01A1 ( U.S. NIH Grant/Contract )
• First Posted: August 2, 2018
• Last Update Posted: August 20, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jiabin Shen, University of Massachusetts, Lowell:

children; executive function; virtual reality; traumatic brain injury

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System