VR-based EF Rehabilitation for Pediatric TBI

• Sponsor: University of Massachusetts, Lowell (Other)
• Overall Status: Completed
• CT.gov ID: NCT03611062
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 27
• Location: 1
• Arms: 2
• Actual Duration (Months): 23.9
• Patients Per Site Per Month: 1.1

Study Details

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	N/A

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
• Actual Enrollment: 27 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: Aug 15, 2018
• Actual Primary Completion Date: Aug 12, 2020
• Actual Study Completion Date: Aug 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. Level of Simulator Sickness [Feasibility and Safety] [Post-Intervention, up to 30 minutes after intervention]

   Measured by the Simulator Sickness Questionnaire. Total scores range from 0 to 26, with 0 representing a better outcome of less sickness.

2. Level of Physical Fatigability [Feasibility and Safety] [Post-Intervention, up to 30 minutes after intervention]

   Measured by the Borg Rating of Perceived Exertion Scale. Total score ranges from 6 to 20, with 6 being a lower amount of exertion.

3. Perceived Virtual Reality Experience [Feasibility] [Post-Intervention, up to 30 minutes after intervention]

   Measured by asking participants to respond to the following question: How much did you like the VR games you just played? Measured on a scale 1-5, with higher values indicating greater enjoyment

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 8, 2019
• Informed Consent Form - Apr 17, 2019

More Information

Publications

None provided.

• Responsible Party: Jiabin Shen, PhD, Principal Investigator, University of Massachusetts, Lowell
• ClinicalTrials.gov Identifier: NCT03611062
• Other Study ID Numbers: IRB18-00472; 1K99HD093814-01A1
• First Posted: Aug 2, 2018
• Last Update Posted: Sep 14, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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, PhD, Principal Investigator, University of Massachusetts, Lowell: children; executive function; virtual reality; traumatic brain injury
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic

Study Results

Participant Flow

Arm/Group Title	VR Executive Functions Training	Control
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.	Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.
Period Title: Overall Study
STARTED	14	13
COMPLETED	13	12
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	VR Executive Functions Training	Control	Total
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.	Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.	Total of all reporting groups
Overall Participants	13	12	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.77 (3.09)	11.75 (3.17)	12.80 (3.23)
Sex: Female, Male (Count of Participants)
Female	5 38.5%	4 33.3%	9 36%
Male	8 61.5%	8 66.7%	16 64%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 8.3%	1 4%
Not Hispanic or Latino	13 100%	11 91.7%	24 96%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 15.4%	2 16.7%	4 16%
White	11 84.6%	9 75%	20 80%
More than one race	0 0%	1 8.3%	1 4%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Level of Simulator Sickness [Feasibility and Safety]
Description	Measured by the Simulator Sickness Questionnaire. Total scores range from 0 to 26, with 0 representing a better outcome of less sickness.
Time Frame	Post-Intervention, up to 30 minutes after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VR Executive Functions Training	Control
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.	Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.
Measure Participants	13	12
Mean (Standard Deviation) [score on a scale]	0.16 (0.19)	0.03 (0.04)

2. Primary Outcome

Title	Level of Physical Fatigability [Feasibility and Safety]
Description	Measured by the Borg Rating of Perceived Exertion Scale. Total score ranges from 6 to 20, with 6 being a lower amount of exertion.
Time Frame	Post-Intervention, up to 30 minutes after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VR Executive Functions Training	Control
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.	Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.
Measure Participants	13	12
Mean (Standard Deviation) [score on a scale]	6.25 (0.50)	11.50 (2.12)

3. Primary Outcome

Title	Perceived Virtual Reality Experience [Feasibility]
Description	Measured by asking participants to respond to the following question: How much did you like the VR games you just played? Measured on a scale 1-5, with higher values indicating greater enjoyment
Time Frame	Post-Intervention, up to 30 minutes after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VR Executive Functions Training	Control
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.	Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.
Measure Participants	13	12
Mean (Standard Deviation) [units on a scale]	3.75 (0.96)	4 (0)

Adverse Events

Time Frame	During the course of the study participation (up to 30 minutes after study completion)
Arm/Group Title	VR Executive Functions Training		Control
Arm/Group Description	Participants will receive training of executive functions in a virtual reality environment. 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.		Participants will play a virtual reality game using the same hardware and similar environments, but without the training of executive functions. 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.
All Cause Mortality
	VR Executive Functions Training		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	VR Executive Functions Training		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	VR Executive Functions Training		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		1/12 (8.3%)
Eye disorders
Blurry vision / eye strain	0/13 (0%)	0	1/12 (8.3%)	1
General disorders
Headache	1/13 (7.7%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.