Evaluating the Effectiveness of Immersive Technologies, Virtual Reality and Augmented Reality, to Increase Pain Threshold During Ice Immersion.
Phase: NA
Conditions: Pain, Neuropathic, Pain, Acute
Sponsor: Stanford University

 
Evaluating the Effectiveness of Immersive Technologies, Virtual Reality and 
Augmented Reality, to Increase Pain Threshold During Ice Immersion 
NCT04196686 
June 10, 2020 
Samuel Rodriguez, MD, Principal Investigator 
Stanford University 
Stanford, California 94305 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
b. 
The purpose of this study is to evaluate the effectiveness of different technologies, 
Virtual Reality and Augmented Reality with modifications as passive content, active 
content, cognitive load modulation, and positive encouragement coaching to increase the 
pain threshold as assessed by immersing a hand in ice water.  
c. 
Rationale for Research in Humans 
This study is designed to test the effectiveness of a virtual distraction on healthy volunteers. There is no 
appropriate substitute for the use of humans in this context, so humans must be used. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
1500 participants (adults, undergraduate, graduate students) recruited by research personal at a booth set up 
on or near the Stanford University campus. They will have the option of completing the study at the booth, 
or scheduling an appointment to participate at LPCH at a later time to do all the study. If interested in the 
study, the research staff will gauge their preferred availability to participate in the study. During the day of 
their scheduled study appointment, the research assistant will review the study, go over the consent forms, 
and answer any questions they may have about the study. Exclusion criteria includes (i) patients who do not 
consent (ii) are currently taking beta blockers or other chronotropic heart medication(s) (iii) have a history 
of severe motion sickness (iv) currently have nausea (v) currently experiencing seizures(vi) are clinically 
unstable (vii) have taken pain medications in the last 12 hours Inclusion criteria includes (i) greater than 18 
years of age (ii)English speaking (iii) hearing intact  
 
PHASE 1  
Part 1a: 3 groups of 250 healthy volunteers will be recruited for this 2 part study. Once they consent to 
participate in the study, the research personnel will do a Sensory perception threshold (time, amplitude) 
captured via biosensors (Neurometer). Then the first group of 250 participants will be randomized into 
either control arm (they will not receive any kind of distraction, no technologies) or the use of Virtual 
Reality. The second group of 250 will be randomized into Active VR, they will play a game or Passive VR, 
they will be watching a movie in the VR headset. And the third group of 250 will be randomized into 
Augmented Reality (AR) or VR. The three groups will wait 5 minutes and each participant will switch to 
the opposite group (i.e. in the first group, VR group will switch to no VR group). Part 1b: Ice bath: 
Participants immerse hand in ice bath and starting again with their original assigned group (see attached 
Dahlquist et al., 2007) and keep hand submerged as long as they can withstand the cold or until 4 minutes 

June 10, 2020 
 
Page 2 of 8 
have elapsed, whichever comes first. Participants will not be told of the specifics of the time limit, to avoid 
competitiveness and expectations and will be asked for pain scores every 30 seconds.  
 
PHASE 2  
Once they consent to participate in the study, the research personnel will do a Sensory perception threshold 
(time, amplitude) captured via biosensors (Neurometer). Part 2a: 250 participants will be recruited and 
randomized into either VR or VR + Cognitive Load Modulation. Cognitive Load Modulation, increase the 
intensity of a game to provide more distraction; the game's audio and visuals will intensify, thereby 
increasing the cognitive load. Ice bath: Participants immerse hand in ice bath and starting again with their 
original assigned group and keep hand submerged as long as they can withstand the cold or until 4 minutes 
have elapsed, whichever comes first. They will be asked to inform research staff when they think they can 
only keep their hand immersed for 5 more seconds at which point the Cognitive Load Modulation (CLM) 
group will have the virtual experience intensity increased, while the controls will not. Participants will not 
be told of the specifics of the 4 minute time limit to avoid competitiveness and expectations. Participants 
will then crossover to the opposite group after a 5 minute rest period.  
 
Part 2b: 
250 participants will be recruited and randomized into either VR or VR with Positive Encouragement 
Coaching (PEC). One of the research assistants will be encouraging the participants to distract them. Ice 
bath: Participants immerse hand in ice bath and starting again with their original assigned group and keep 
hand submerged as long as they can withstand the cold or until 4 minutes have elapsed, whichever comes 
first. They will be asked to inform research staff when they think they can only keep their hand immersed 
for 5 more seconds at which point the PEC VR group will have the virtual experience intensity increased, 
while the controls will not. Participants will not be told of the specifics of the 4 minute time limit to avoid 
competitiveness and expectations. Participants will then crossover to the opposite group after a 5 minute 
rest period.  
 
Part 2c: 250 participants will be recruited and randomized into either CLM VR or PEC VR Ice bath: 
Participants immerse hand in ice bath and starting again with their original assigned group and keep hand 
submerged as long as they can withstand the cold or until 4 minutes have elapsed, whichever comes first. 
They will be asked to inform research staff when they think they can only keep their hand immersed for 5 
more seconds at which point the PEC VR group and the CLM VR groups will have the virtual experience 
intensity increased, while the VR only will not. Participants will not be told of the specifics of the 4 minute 
time limit to avoid competitiveness and expectations. Participants will then crossover to the opposite group 
after a 5 minute rest period. All the technologies: VR headset/AR headsets have been approved and meet 
standards established by the Hospital Instrument and Electrical Safety Committee and are currently in use 
in the perioperative department. All participants will have biometric sensors that will be collecting 
physiological metrics such as vital signs, heart rate variability, respiratory rate, etc., which will be entered 
into a REDCap database. The study will be conducted in LPCH and SHC facilities and clinics. 
 
We use a calculator to determine the minimum number of subjects that need to be enrolled in a study in 
order to have sufficient statistical power to detect a treatment effect. For 2 independent sample study with 
mean of 7(SD of 1.5) in group 1, mean of 9 in group 2, alpha of 0.05, beta of 0.2 and power of 0.8, 10 
patients will be required in each group. To compensate for dropouts and incomplete data, 12 patients are 
targeted for enrollment in each group. After enrolling the first 24 participants we ran statistics test to 
calculate the sample size if we want to have sufficient statistical power with the data we collected. The new 
sample size needs to be 250 participants in each group.  
 
b. 
Procedure Risks 

June 10, 2020 
 
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Using AR/VR carries minimal risk. The main risk is developing nausea and/or dizziness, which will be 
monitored for and can be easily treated by removing the headset. Ice bath protocols have been performed 
for decades and we will adhere to safety standards set by these protocols such as constant monitory of ice 
bath temperature via thermometer, hard time limit, rest period between phases, and heart rate monitoring 
via pulse oximeter.  
 
c. 
Use of Deception in the Study 
NA 
d. 
Use of Audio and Video Recordings 
NA 
e. 
Alternative Procedures or Courses of Treatment 
This does not involve specific treatments. No standard treatment will be withheld, the alternative to this 
study is for the participant not to engage in our research study. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
Yes - VR/AR technologies described here are currently in use for the entire hospital. 
g. 
Study Endpoint(s) 
The endpoint of the study will be determined by the completion of the target number of participants. The 
target number of participants 1500. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
While there have been previous studies that evaluate virtual distraction for decreasing pain in the medical 
setting, to our knowledge this will be the first to evaluate the effectiveness of several modifications 
including augmented reality, cognitive load modulation, and positive encouragement coaching.  
 
[1] Tsui, B. C., Shakespeare, T. J., Leung, D. H., Tsui, J. H., & Corry, G. N. (2013). Reproducibility of 
current perception threshold with the Neurometer® vs the Stimpod NMS450 peripheral nerve stimulator in 
healthy volunteers: an observational study. Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 
60(8), 753-760. 
 
[2] Dahlquist, L. M., Herbert, L. J., Weiss, K. E., & Jimeno, M. (2010). Virtual-reality distraction and cold-
pressor pain tolerance: does avatar point of view matter?. Cyberpsychology, Behavior, and Social 
Networking, 13(5), 587-591. 
 
[3] Dahlquist, L. M., McKenna, K. D., Jones, K. K., Dillinger, L., Weiss, K. E., & Ackerman, C. S. (2007). 
Active and passive distraction using a headmounted display helmet: Effects on cold pressor pain in 
children. Health Psychology, 26(6), 794. 
 
[4] Forys, K. L., & Dahlquist, L. M. (2007). The influence of preferred coping style and cognitive strategy 
on laboratory-induced pain. Health psychology, 26(1), 22. 
 

June 10, 2020 
 
Page 4 of 8 
[5] Dahlquist, L. M., Pendley, J. S., Landtrip, D. S., Jones, C. L., & Steuber, C. P. (2002). Distraction 
intervention for preschoolers undergoing intramuscular injections and subcutaneous port access. Health 
Psychology, 21(1), 94. 
 
[6] Gershon, J., Zimand, E., Pickering, M., Rothbaum, B. O., & Hodges, L. (2004). A pilot and feasibility 
study of virtual reality as a distraction for children with cancer. Journal of the American Academy of Child 
& Adolescent Psychiatry, 43(10), 1243- 1249. 
 
b. 
Findings from Past Animal Experiments 
 
4. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
Investigational Device 1 
Name: 
Virtual Reality Headset-Gear VR 
Description: 
Portable VR headset to display a passive relaxing 
experience such as sitting on beach or exploring the 
ocean by looking around. The active experience may 
include playing a game to collect bananas as monkey, 
flying a paper airplane, or catching balls in a basket. 
 
Significant Risk? (Y/N) 
N 
Rationale for Non-Significant Risk 
VR headsets are commercially available devices for 
gaming and relaxation with insignificant risks. The 
possible side effects are nausea and dizziness, they can be 
solve with removing the headset. 
 
 
5. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
(i) 1500 participants will be enrolled during our study 
(ii) Students, adults, visitors and personnel working or volunteering at LPCH or SHC facilities 
(iii) These participants are being chosen because we are focusing on a low risk population 
b. 
Age, Gender, and Ethnic Background 
Patients 18 and older of mixed genders and ethnic backgrounds. 
c. 
Vulnerable Populations 
Up to 1500 healthy volunteers, students, adults, visitors and personnel working or volunteering at LPCH or 
SHC facilities could potentially be enrolled in this study. This is necessary as this study aims to investigate 
the effectiveness of non-invasive technologies (AR/VR/Tablet) with modifications at altering pain 
tolerance. . Although we expect minimal risks in this study, there may be a chance of patients experiencing 
intolerable symptoms such as dizziness and nausea from VR/AR use. In such case our health care providers 
will be notified and appropriate measures will be taken to ensure patient safety. The risk discovery of an 
individual's participation is mitigated by our measures to keep patients data de-identified and stored in a 
secure and encrypted database. 

June 10, 2020 
 
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d. 
Rationale for Exclusion of Certain Populations 
NA 
e. 
Stanford Populations 
Up to 1500 volunteers could be enrolled in the study. 
f. 
Healthy Volunteers 
NA 
g. 
Recruitment Details 
School of Medicine research assistants who are not affiliated with the volunteers in any way, will recruit 
via an informational booth set up on the Stanford Campus after receiving University approval and at LPCH. 
At the booth and at LPCH some research assistant will be running the study and other research assistants 
will be around to booth to inform the people about the study. The research assistants will not coerce or 
influence an volunteer's decision to participate. If volunteer declines interest, research personnel will 
respect their decision and will not pursue them for any further involvement in this study. 
 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
(i) greater than 18 years of age (ii) English speaking (iii) hearing intact 
 
ii. 
Exclusion Criteria 
(i) patients who do not consent 
(ii) are currently taking beta blockers or other chronotropic heart medication(s) 
(iii) have a history of severe motion sickness 
(iv) currently 
have nausea 
(v) currently experiencing seizures 
(vi) are clinically unstable 
 
i. 
Screening Procedures 
No PHI will be collected prior to enrollment. If the participant expresses interest they will be approached 
by a research assistant. If they decline they will not receive any further information about the study. If the 
participant expresses interest, the RA will proceed with the consent and appropriate stage placement, 
randomization will occur for the second phase (either standard of care of VR/AR/table simulation) If the 
potential candidate declines interest, we will respect their decision and will not pursue them for any further 
involvement in this study. Only authorized members of the study team will have access to patient 
information. 
 
j. 
Participation in Multiple Protocols 
Participants will be asked if they are participating or intend to enroll in other studies. Participants will be 
allowed to participate in more than one study if it can be determined that this poses no increased risk to the 

June 10, 2020 
 
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participants or the integrity of the data collected for either study. 
 
k. 
Payments to Participants 
Participants will receive a $5.00 gift card for participation in this study. 
l. 
Costs to Participants 
NA 
m. 
Planned Duration of the Study 
i) Screening per patient will take approximately 10-15 minutes. 
ii) Active participation for the participant will last the duration of the procedure, we estimate about 1 hour, 
from the time of consent to the debrief. 
iii) The analysis of the data will take approximately 1-2 years. 
 
6. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
VR and AR headset and software- we expect a low incidence of intolerability (primarily nausea and 
dizziness) in less than 5% of all cases, in which case VR headset can simply be removed and any follow-up 
care can be assessed by the healthcare provider. 
ii. 
Investigational drugs 
NA 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
NA 
iv. 
Procedures 
The VR and AR headsets unit will be placed on patients by trained staff and will have minimal risk to the 
patient. VR and AR headsets will be set up by trained study staff. All devices are wiped with hospital grade 
disinfection wipes according to hospital protocols. All devices are compliant with infection control 
standards at LPCH and hospital instrument and electrical compliance. 
 
v. 
Radioisotopes/radiation-producing machines 
NA 
vi. 
Physical well-being 
NA 
vii. 
Psychological well-being 
NA 

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viii. 
Economic well-being 
NA 
ix. 
Social well-being 
NA 
x. 
Overall evaluation of risk 
NA 
b. 
International Research Risk Procedures 
NA 
c. 
Procedures to Minimize Risk 
Participants/patients will be informed that they may withdraw from the study at any time, for any reason, 
with no consequences for withdrawing, and the standard clinical care and procedures for their care will 
continue as normal. All data will be de-identified and stored in a secure, encrypted database for clinical 
analysis. 
 
d. 
Study Conclusion 
The experiment will terminate at the conclusion or enrollment. There is no anticipated interim analysis, and 
no reason to consider early termination based on the low level of risk associated with this study. If the 
patient decides that he/she does not want to participate in the study at any time, we will terminate the study. 
 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
NA 
ii. 
Person(s) responsible for Data and Safety Monitoring 
NA 
iii. 
Frequency of DSMB meetings 
NA 
iv. 
Specific triggers or stopping rules 
NA 
v. 
DSMB Reporting 
NA 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
NA 

June 10, 2020 
 
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vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
NA 
f. 
Risks to Special Populations 
NA 
7. 
BENEFITS 
It is unknown if participants enrolled in the study will directly benefit, but we anticipate that the 
technology-based distractions have great potential to be used in future medical encounters. 
8. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health.