Headaches Posttraumatic, Pain, Acute, Trauma, Traumatic Brain Injury
Conditions
Brief summary
Severe and refractory pain after acute injury is a known-risk factor for chronic opioid use disorder. In this study, the investigators will use Virtual Reality (VR) immersion as a non-pharmacological adjunct to treat pain associated with acute traumatic injuries, including traumatic brain injury. The investigators hypothesize that VR therapy will decrease pain and reduce opioid use in patients with acute traumatic injuries, including TBI.
Detailed description
Each participant will undergo one VR session and two control sessions. The VR session will take place in a commercially available VR environment, the Blu, and last 20-30 minutes (VR Blu). The control sessions will include a 2D-tablet based session that mimics the VR content (Tablet Blu) and a content-less placement of the VR headset (VR Blank). The order of these sessions will be randomized across participants are intended to complete all sessions. Each participant will complete a pre-study questionnaire to elicit their prior experience with the virtual reality as well as measures of gaming addiction/engagement, boredom, and expectancy. These scales will help us determine which patient-level factors predict response to VR. Before and after each session, participants will complete validated scales of pain, nausea, and anxiety.. Pre- and Post-VR opioid use will be recorded. Basic vital signs including heart rate, blood pressure, and respiratory rate, will be recorded before and after each session to monitor autonomic response. Advanced measures of autonomic response will include heart rate variability,,and pupillometry metrics. At the conclusion of all sessions, participants will complete another questionnaire to document their subjective experience of using VR (perceived effectiveness)
Interventions
BEHAVIORALVirtual Reality Session (VR Blu)
20-30 minute session of virtual reality immersive content.
BEHAVIORALTablet-based Session (Tablet Blu)
20-30 minute session of tablet-based content that mimics the content from virtual reality sessions.
BEHAVIORALUse of Virtual Reality Head Mounted Display without Content (VR Blank)
20-30 minutes session using head mounted display to reduce light and sound.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Interventions will take place in patient rooms with curtain pulled and sign to mask active intervention vs. control intervention from care providers.
Intervention model description
Within-Subjects Design. All participants (single group, 1 arm) intended to complete all three sessions (interventions) in randomized order. At least 4 hours were required to pass between each session to allow for washout.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Traumatic Injury (including but not limited to traumatic brain injury) * Age greater than or equal to 18 years-old * Endorsing at least moderate pain as defined by documentation of at least one numeric rating pain scale score of 3 or more in the last 24 hours. * Glasgow Coma Scale of 15 * Expected to stay in the hospital for at least 12 hours after enrollment
Exclusion criteria
* Seizure prior to enrollment * Pregnancy * non-English speaking * Known intolerance of Virtual Reality * Patient unable to consent for themselves
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Score | Pre- and Post-Intervention (approximately 30 minutes) | Pre- vs. Post-Intervention Ratings on Numeric Pain Rating Scale. Numeric Pain Rating scale range is from 0 (no pain) -10 (severe pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Administration | 4 hours post-intervention vs. 4 hours pre-intervention | Change in amount of opioids received in the 4 hours post-intervention vs. the 4 hours pre-intervention in morphine equivalents |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Anxiety | Pre- and Post-Intervention (approximately 30 minutes) | Pre- vs. Post-Intervention Anxiety Ratings from Short-Form State Anxiety Inventory. Scores Range from 6 (Not at all anxious) - 24 (Very much amxious) |
| Change in Pupillometry | Pre- and Post-Intervention (approximately 30 minutes) | Pre- vs. Post-Intervention Pupillary Maximum Constriction Velocity. Reduced pupillary maximum constriction velocity is representative of decreased parasympathetic nervous system activity. |
| Subjective Measures of VR Experience | Pre- and Post-study (approximately 2-3 days) | A Likert-Scale questionnaire was used to assess participant's subjective ratings of how effective the interventional sessions were. The scale ranged from 0 (not at all) to 5 (very much). |
| Change Heart Rate Variability | Mean NN from last 15 minutes of each intervention compared to mean NN from 15 minutes immediately prior to intervention | Pre- vs. Post-Intervention Heart Rate Variability as measured by normal-to-normal (NN) means. Decreasing NN means are associated with the activity of sympathetic system, while increasing NN means means are associated with the activity of parasympathetic nervous system |
| Change in Nausea | Pre- and Post-Intervention (approximately 30 minutes) | Pre- vs. Post-Intervention Ratings on Numeric Rating Scale for Nausea. Numeric Rating Scale for Nausea ranges from 0 (no nausea) - 10 (worst nausea possible) |
Countries
United States
Participant flow
Recruitment details
2083 patients were screened for eligibility between October 2020 and January 2022 in a dedicated trauma hospital. 1885 patients were excluded. 138 patients declined to participate in the study. 60 patients were enrolled in the study. All patients were intended to participate in all conditions (in randomized order) including: VR Blu, Tablet Blu, VR Blank.
Pre-assignment details
All 60 patients were intended to participate in all 3 conditions in randomized order. 60 of 60 patients had session order randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Patients Patients engaged in three different 20 min sessions run by research coordinators and spaced a minimum of 4 hours apart, including 1) a commercially available, immersive VR environment, theBlu (WEVR, Inc, Venice, California, USA) delivered via Oculus Rift (Oculus VR, Irvine, California, USA) headset, 2) a non-immersive two-dimensional mimic delivered via a tablet computer, and 3) a VR control session delivered via a content-less Oculus Rift headset. The three sessions were run by research coordinators and spaced a minimum of 4 hours apart. The intervention order was counterbalanced using a randomized sequence generator. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| First Session | Withdrawal by Subject | 1 |
| Second Session | Lost to Follow-up | 1 |
| Second Session | Withdrawal by Subject | 3 |
| Third Session | Lost to Follow-up | 6 |
| Third Session | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Acute Injury Scale > 0 Abdominal | 29 participants |
| Acute Injury Scale > 0 Face | 20 participants |
| Acute Injury Scale > 0 Head | 29 participants |
| Acute Injury Scale > 0 Head with Traumatic Brain Injury | 20 participants |
| Acute Injury Scale > 0 Lower Extremity | 35 participants |
| Acute Injury Scale > 0 Neck | 8 participants |
| Acute Injury Scale > 0 Spine | 15 participants |
| Acute Injury Scale > 0 Thoracic | 26 participants |
| Acute Injury Scale > 0 Upper Extremity | 28 participants |
| Age, Continuous | 53 years |
| Health Insurance Medicaid | 5 Participants |
| Health Insurance Medicare | 16 Participants |
| Health Insurance Private | 39 Participants |
| Past Medical History Alcohol Abuse | 13 participants |
| Past Medical History Anxiety | 16 participants |
| Past Medical History Chronic Pain | 13 participants |
| Past Medical History Depression | 18 participants |
| Past Medical History Positive Toxicology Screen | 32 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 37 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 42 Participants |
| Type of Traumatic Brain Injury Epidural hematoma | 1 participants |
| Type of Traumatic Brain Injury Intracerebral Hemorrhage | 13 participants |
| Type of Traumatic Brain Injury Subarachnoid hemorrhage | 8 participants |
| Type of Traumatic Brain Injury Subdural hematoma | 10 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 54 |
| other Total, other adverse events | 0 / 54 |
| serious Total, serious adverse events | 0 / 54 |
Outcome results
Primary
Change in Pain Score
Pre- vs. Post-Intervention Ratings on Numeric Pain Rating Scale. Numeric Pain Rating scale range is from 0 (no pain) -10 (severe pain)
Time frame: Pre- and Post-Intervention (approximately 30 minutes)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change in Pain Score | VR Blu Intervention Pain Reduction | -0.92 score on a scale | Standard Error 0.33 |
| All Patients | Change in Pain Score | Tablet Blu Intervention Pain Reduction | -0.16 score on a scale | Standard Error 0.29 |
| All Patients | Change in Pain Score | VR Blank Intervention Pain Reduction | -1.24 score on a scale | Standard Error 0.33 |
Secondary
Opioid Administration
Change in amount of opioids received in the 4 hours post-intervention vs. the 4 hours pre-intervention in morphine equivalents
Time frame: 4 hours post-intervention vs. 4 hours pre-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Opioid Administration | Changes in opioid dose received after VR Blu condition | -0.159 morphine milligram equivalents | Standard Error 1.392 |
| All Patients | Opioid Administration | Change in opioid dose received after Tablet Blu | -0.89 morphine milligram equivalents | Standard Error 1.175 |
| All Patients | Opioid Administration | Change in opioid dose received after VR Blank | -0.059 morphine milligram equivalents | Standard Error 1.341 |
Other Pre-specified
Change Heart Rate Variability
Pre- vs. Post-Intervention Heart Rate Variability as measured by normal-to-normal (NN) means. Decreasing NN means are associated with the activity of sympathetic system, while increasing NN means means are associated with the activity of parasympathetic nervous system
Time frame: Mean NN from last 15 minutes of each intervention compared to mean NN from 15 minutes immediately prior to intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change Heart Rate Variability | VR Blu induced change in mean NN (NN from last 15 min of session minus NN 15 min pre-session) | 874.64 ms | Standard Error 15.36 |
| All Patients | Change Heart Rate Variability | Tablet Blu induced change in mean NN (NN from last 15 min of session minus NN 15 min pre-session) | 834.78 ms | Standard Error 1.93 |
| All Patients | Change Heart Rate Variability | VR Blank induced change in mean NN (NN from last 15 min of session minus NN 15 min pre-session) | 867.64 ms | Standard Error 10.37 |
Other Pre-specified
Change in Anxiety
Pre- vs. Post-Intervention Anxiety Ratings from Short-Form State Anxiety Inventory. Scores Range from 6 (Not at all anxious) - 24 (Very much amxious)
Time frame: Pre- and Post-Intervention (approximately 30 minutes)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change in Anxiety | changes in STAI score after VR Blue | -.061 score on a scale | Standard Error 0.311 |
| All Patients | Change in Anxiety | Changes in STAI score after Tablet Blue | -0.401 score on a scale | Standard Error 0.32 |
| All Patients | Change in Anxiety | Changes in STAI score after VR Blank | -0.675 score on a scale | Standard Error 0.501 |
Other Pre-specified
Change in Nausea
Pre- vs. Post-Intervention Ratings on Numeric Rating Scale for Nausea. Numeric Rating Scale for Nausea ranges from 0 (no nausea) - 10 (worst nausea possible)
Time frame: Pre- and Post-Intervention (approximately 30 minutes)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change in Nausea | Change in nausea after VR Blu | -0.116 score on a scale | Standard Error 0.304 |
| All Patients | Change in Nausea | Change in nausea after Tablet Blu | -0.395 score on a scale | Standard Error 0.248 |
| All Patients | Change in Nausea | Change in nausea after VR Blank | -0.093 score on a scale | Standard Error 0.057 |
Other Pre-specified
Change in Pupillometry
Pre- vs. Post-Intervention Pupillary Maximum Constriction Velocity. Reduced pupillary maximum constriction velocity is representative of decreased parasympathetic nervous system activity.
Time frame: Pre- and Post-Intervention (approximately 30 minutes)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change in Pupillometry | VR Blue change in maximum constriction velocity | 0.187 mm/s | Standard Error 0.112 |
| All Patients | Change in Pupillometry | Tablet Blue change in maximum constriction velocity | -0.047 mm/s | Standard Error 0.097 |
| All Patients | Change in Pupillometry | VR Blank change in maximum constriction velocity | -0.299 mm/s | Standard Error 0.149 |
Other Pre-specified
Subjective Measures of VR Experience
A Likert-Scale questionnaire was used to assess participant's subjective ratings of how effective the interventional sessions were. The scale ranged from 0 (not at all) to 5 (very much).
Time frame: Pre- and Post-study (approximately 2-3 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Subjective Measures of VR Experience | Tablet Blu Perceived Effectiveness on Likert Scale (0-5, not at all effective - very effective) | 2.68 score on a scale | Standard Error 0.23 |
| All Patients | Subjective Measures of VR Experience | VR Blank Perceived Effectiveness on Likert Scale (0-5, not at all effective - very effective) | 1.52 score on a scale | Standard Error 0.29 |
| All Patients | Subjective Measures of VR Experience | VR Blu Perceived Effectiveness on Likert Scale (0-5, not at all effective - very effective) | 3.63 score on a scale | Standard Error 0.23 |