Neurocognitive Driving Rehabilitation in Virtual Environments (NeuroDRIVE) as an Adjunctive Intervention for Traumatic Brain Injury

OBJECTIVE:

The primary objective of this study is to evaluate the NeuroDRIVE behavioral intervention for
enhancement of driving abilities, cognitive abilities, and neurobehavioral symptoms after
traumatic brain injury (TBI). For the purposes of this protocol, NeuroDRIVE refers to the
novel combined approach of driving training and cognitive rehabilitation in a virtual reality
environment. While NeuroDRIVE utilizes the VR system as the method through which the
intervention is administered, NeuroDRIVE is not the VR system itself.

STUDY POPULATION:

30 adult patients with a history of mild TBI and 30 adult patients with a history of
moderate-to-severe TBI. Participants will be recruited from the National Institutes of Health
(NIH), WRNMMC, and the broader community.

DESIGN:

The current study is a Clinical Trial Phase II interventional research study. The primary
purpose of the study is for treatment, and it will employ a parallel intervention model.
There will be no masking (i.e., open label). Participants will be classified into two groups
by TBI severity: those with history of mild TBI and those with history of moderate-tosevere
TBI. These different severities are known to have distinct cognitive sequelae. Within each
severity group, participants will be in a 2 (pre-post) x 2 (treatment vs. wait list)
experimental design.

OUTCOME MEASURES:

Primary outcome measures will include:

- Results from the Virtual Reality Driving Assessment (baseline and postintervention
Tactical scenario composite scores)

- Total scores on the Neurobehavioral Symptom Inventory

- Standard and scaled scores from the following cognitive assessments (from the TBI Common
Data Elements identified by NINDS):

WAIS-IV or WMS-IV Digit Span subtest

WAIS-IV Digit-Symbol Coding subtest

Secondary outcome measures will include:

-Neuroimaging results:

Regions of Interest for FMRI: Bilateral dorsolateral prefrontal cortex

Regions of Interest for DTI: Corpus callosum, bilateral frontal white matter horns, and
bilateral longitudinal fasciculi

-Total scores on the following symptom questionnaires:

Glasgow Outcome Scale-Extended (GOS-E)

Ohio State University TBI Identification Method

Brief Symptom Inventory- 18

Satisfaction with Life Scale (SWLS)

PTSD Checklist- Civilian (PCL-C)

SF-36v2 Health Survey (SF-36v2)

Fatigue Severity Scale (FSS)

Epworth Sleepiness Scale (ESS)

Beck Depression Inventory-II (BDI-II)

Combat Exposure Scale (CES)

Dual Dangerous Driving Index (DDDI)

-Standard and scaled scores from the following cognitive phenotyping assessments (from the
TBI Common Data Elements identified by NINDS):

California Verbal Learning Test- Second Edition (CVLT-II)

WAIS-IV Symbol Search subtest

Medical Symptom Validity Test (MSVT)

-Standard and scaled scores from the following additional cognitive phenotyping assessments:

Trail Making Test (TMT)

Test of Premorbid Functioning (ToPF)

Grooved Pegboard

Controlled Oral Word Association Test (COWAT)

Bethesda Eye and Attention Measure (BEAM)

- INCLUSION CRITERIA:

Subjects eligible for participation must meet the following criteria:

1. Currently has a valid driver s license, or had a valid driver s license prior to
injury

2. 18 years of age or older

3. Able to effectively manipulate the steering wheel and the gas/brake pedals without
adaptive equipment

4. Able to read, write, and speak in English

5. History of traumatic brain injury greater than 12 weeks prior to initiation into the
current study

6. Able to provide informed consent

7. NBSI score greater than or equal to 16 (Mild TBI sub-group only)

EXCLUSION CRITERIA:

Subjects are not eligible for participation if any of the following conditions exist:

1. Risk for injury from the MRI magnet, including:

- Pacemakers or other implanted electrical devices.

- Brain stimulators.

- Some types of dental implants.

- Aneurysm clips (metal clips on the wall of a large artery).

- Metallic prostheses (including metal pins and rods, heart valves, and cochlear
implants).

- Permanent eyeliner (other non-metallic tattoos are permissible).

- Implanted delivery pump.

- Shrapnel fragments.

- Welders and metal workers are also at risk for injury because of possible small
metal fragments in the eye of which they may be unaware.

- Fear of confined spaces.

- Back problems that may result in back pain or discomfort from lying in the
scanner.

- Weight of over 350 pounds, due to the weight limit of the MRI table.

- It is not known if MRI is completely safe for a developing fetus. Therefore, all
women of childbearing potential will have a pregnancy test performed no more than
24 hours before each MRI scan. The scan will not be done if the pregnancy test is
positive. Because neuroimaging is a key component of the current study, inability
to participate in MRI scanning is a necessary exclusion criterion.

2. History of penetrating brain injury

3. History of serious medical condition other than TBI that could affect cognitive or
motor abilities (e.g., multiple sclerosis, encephalitis, cerebrovascular disease)

4. History of severe motion sickness and/or vertigo.

5. Other medical or psychological instability that could create difficulty fulfilling the
study requirements (e.g., untreated mental illness, auditory/visual hallucinations,
narcolepsy)

To verify this information, study coordinators will request medical records (i.e., recent
medical history, medication list, any neuroimaging, and records pertinent to the
participant s recent injury) to further evaluate potential participants inclusion into the
study. Medical records can be obtained in three ways:

1. Participants can bring the records when they come to NIH for testing; it will be made
clear if they do not bring this information with them and we cannot verify that they
meet inclusion criteria, potential participants will not be enrolled into the study
that day.

2. Alternatively, the participants can also fax their medical records to a secured fax
machine at the Recreational Therapy office at the NIH where access is only permitted
to study staff (i.e., scheduler, physician, and nurse psychologist).

3. Participants may also fill out a medical release document and submit it to the study
coordinator.

Medical history data will be reviewed, and if it is clear that the patient does not meet
the inclusion criteria, we will contact them and cancel their appointment. Data obtained in
this manner may be used to evaluate participant eligibility; however, it will not be used
for any research purposes. Additionally, for any patients who are deemed not eligible to
participate, their medical history data will be destroyed in accordance with NIH
regulations.

As a condition of receiving funding from CNRM, de-identified imaging and phenotyping data
(i.e., neurocognitive test results and behavioral questionnaires) from funded studies must
be made available within a centralized repository (the CNRM Informatics Core) one year
after the completion of the study. This is intended to facilitate use and analysis of this
data for future research questions or projects. As such, potential subjects will be
informed that they should not participate in this study if they do not want their data used
for other projects.