Study on the Use of Virtual Reality Neuropsychological Therapy Technology (VRNT) for Chronic Back Pain
Phase: NA
Conditions: Chronic Pain, Back Pain Lower Back Chronic, Back Pain
Sponsor: CognifiSense Inc.

 
 
 
 
STUDY BRIEF TITLE:   Virtual Reality Treatment for Adults With Chronic Back Pain 
 
NCT:   NCT04468074 
 
 
 
DOCUMENT TITLE:  STUDY PROTOCOL 

 
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TITLE:  Study on the Use of Virtual Reality Neuropsychological Therapy Technology 
(VRNT) for Chronic Back Pain 
 
PROTOCOL VERSION DATE: August 29, 2020 
VERSION: 4 
PRINCIPAL INVESTIGATOR (PI):  
Name: Marta Ceko 
KEY PERSONNEL 
Name: Tassilo Baeuerle 
Role in project: Co-Investigator (CognifiSense, Inc.) 
 
Name: Lynn Webster, MD 
Role in project: Co-Investigator (CognifiSense, Inc.) 
 
 
GENERAL RESEARCH STAFF 
Two undergraduate/graduate research assistants will assist with this protocol at a time. 
The PI will ensure appropriate CITI and protocol specific training is maintained. General 
Research Staff responsibilities will include distributing flyers, administering survey 
instruments, assisting with fMRI scanning, and data entry.  
 

 
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I. 
OBJECTIVES 
The purpose of this study is to determine the clinical feasibility of a new virtual reality 
therapy, called Virtual Reality Neuropsychological Therapy (VRNT), in achieving 
lasting pain reduction in moderate to severe chronic back (CBP) patients, and to collect 
user feedback to help further refine the current product prototype. 
 
• Primary objective of the study is to test the efficacy of VRNT in CBP patients. 
Specifically, we will determine to what extent VRNT: (1) Has a cumulative effect in 
decreasing pain and increasing function over an 8-week period; and (2) Once 
discontinued, has any lasting effects (2 weeks).  
 
• Secondary objective of the study is to establish brain mechanisms associated with 
treatment response: (1) Establish neurobiological correlates of improvement in pain 
and disability, (2) Establish brain mechanisms for treatment response at the brain 
systems level.  
 
II. 
BACKGROUND AND SIGNIFICANCE  
 
 
Chronic pain affects 100 million Americans, ~45 million of whom are considered to 
have “high impact chronic pain” (Van Korff et al. 2016), characterized by added 
psychological burden and perceived lack of control over pain. Traditional pharmacological 
treatments carry serious potential side-effects, and some carry a risk of addiction. Opioids 
commonly prescribed for chronic pain only have a ~30% responder rate (Santos et al. 
2015). Some non-pharmacological approaches, such as Cognitive Behavioral Therapy 
(CBT), seek to address psychological factors contributing to pain, but are expensive, often 
inaccessible to rural patients, and rely heavily on provider training / quality; i.e., they show 
a broad range of efficacy and are thus difficult to scale. CognifiSense, Inc. has developed 
a full working prototype of a patented, new virtual reality therapy called Virtual Reality 
Neuropsychological Therapy (VRNT) aimed at providing a lasting reduction in chronic 
pain. Unlike centrally acting analgesics, which mainly affect patients’ immediate pain 
experience and comfort, VRNT is designed to address the underlying maladaptive 
neuroplastic changes associated with chronic pain to create a lasting reduction in pain. 
During the transition from acute to chronic pain the experience of pain shifts from 
a largely proportionate response to a nociceptive pain stimulus to a complex set of learned 
emotional-motivational factors driving the pain experience. The brain is, thus, in a state 
of continuous learning, in which persistent, inextinguishable pain leads the brain to 
continuously make aversive emotional associations; e.g., the brain may catastrophize, 
hyper-sensitize, or even “expand”/”move” pain, and it may do this long after the 
nociceptive source has healed. The inability to extinguish the pain helps to sustain this 
maladaptive cycle of learning (Mansour et al. 2014). The response to nociceptive 
stimulation is affected by the degree to which pain is perceived to be controllable, and 
self-efficacy can modulate pain tolerance and the ability to cope with intractable pain. 
Fear and avoidance are important contributors to the maladaptive learning cycle in 
chronic pain, as they lead to pain catastrophizing, hypervigilance, disuse, depression and 

 
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disability; all of these, in turn, drive the pain experience (Vlaeyen et al. 2012). Thus, for 
any lasting change in chronic pain, therapies must address these maladaptive learning 
processes; they must incorporate relearning (Flor et al. 2012) self-efficacy and 
extinguishing fear of pain. VRNT is a non-pharmacological, software-based pain therapy 
which aims to do exactly this.  
 
III. 
PRELIMINARY STUDIES  
Research on therapies focusing on pain control, pain extinction and self-efficacy 
indicates that visual perception of body and pain have an important relationship with pain 
perception, and that manipulating imagery associated with pain and body can reduce pain 
in chronic pain patients (Moseley et al. 2008, Ramachandran et al. 2009, Foell et al. 
2013).  
VRNT provides the brain with a new set of signals intended to interrupt chronic 
pain’s maladaptive learning cycles and replace it with positive learning cycles. VRNT 
provides the brain with new signals.  
Through repeated use of the complete set of modules, VRNT is intended to 
condition the brain to reflexively use new pain perceptions and new protocols for pain 
control or response. It is, thus, intended to provide the brain with tools to interrupt the 
constant maladaptive associations. VRNT also seeks to interrupt the maladaptive fear-
avoidance cycle.  Finally, VRNT provides patients with reassessment modules during 
which patients learn to reassess the meaning of different pain sensations and emotions.   
 
IV. 
RESEARCH STUDY DESIGN  
This study has 4 phases and will take ~6 months to complete.  During the study 
participants will be randomized into two groups: Therapy Group and Waitlist Group. The 
Therapy Group will complete 5 surveys. The Waitlist Group will complete 8 surveys; each 
survey consists of multiple questionnaires, which will be administered on-line via 
Qualtrics.  The study also includes 2 MRI scans. There will be 3 in-person sessions: MRI 
Scan #1 and #2, and one in-person VRNT Practice Session [all but the MRI scans were 
moved to a video call format as a result of the University’s updated COVID-19 protocols].  
There will also be two video-call sessions:  one educational session and one Therapy 
Personalization session. In addition, participants will be scheduled for 8 weekly calls (~30 
minutes) during the Therapy Period.  Note:  Participants who are assigned to the Waitlist 
will be asked to schedule one more very short visit to CINC to drop off the virtual reality 
equipment.  Figures 1 and 2 provide an overview of the study. 
 
 

 
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Figure 1.  Study Design. Phases 1-3 (All participants participate in these phases). 
 
 
 
Figure 2.  Study Design. Phase 4 (Waitlist Group participants only).  
 
 
Phases: 
 
Phase 1:  Collect (pre-therapy) baseline data on all outcome measures from all 
participants.  A 2-week Baseline Period is used to average out day-to-day fluctuations in 
participant pain experiences.  Data on certain outcome measures are collected before 
and after the Baseline Period to allow us to determine if there are any change due to 
simply participating in the Baseline. The first MRI session will be after the Baseline Period. 
Participants are randomized into a Therapy Group and a Waitlist Group at the end of 
Phase 1. 

 
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Phase 2:  8-week Therapy Period in which the Therapy Group receives VRNT; The 
Waitlist Group will receive the Therapy in Phase 4.  The same data is collected from both 
groups.  Exception: at the end of Phase 2 (in Survey #4), the Therapy Group completes 
additional questionnaires about their experience with VRNT (e.g., usability). This phase 
also includes the second MRI session.  Finally, this phase includes 8 weekly calls (~30 
minutes)) to track adherence / compliance / problems, answer participant questions, and 
to provide participants with more explanation of upcoming modules. 
 
Phase 3:  2-week Follow-Up Period to determine if there is a lasting VRNT effect in the 
Therapy Group.  The same data is collected from both groups.  The study ends for the 
Therapy Group at the completion of Phase 3. 
 
Phase 4:  The purpose of this Phase is to allow the Waitlist Group to receive VRNT.  
Phase 4 includes both the 8-week Therapy Period and the 2-Week Follow-Up period.  
Data will be collected to evaluate any change in outcome measures (e.g. pain reduction); 
however, there is no direct control group in this Phase, therefore this data will be 
considered exploratory (longitudinal within-group changes not controlling for non-specific 
effects and natural history).  Phase 4 does not include another MRI scan (post-Therapy) 
for the Waitlist Group, because a) there is no direct comparison group (e.g., we are not 
investigating the potential effects of being in the Waitlist Group, but differences in 
Treatment between the Therapy Group and Waitlist Group), and b) limited funding under 
the grant. 
 
 
Data Collected (by Aim) 
 
Aim 1:  Data will be collected on each participant’s pain intensity and the impact of CBP 
on the participant’s life to determine changes between Baseline, end of Therapy Period 
and end of Follow-Up Period: 
 
1. Primary Outcome Measure: The impact of VRNT on pain intensity will be 
measured using: 
a. Brief Pain Inventory – Short Form (BPI-SF), which is a commonly used 
standardized pain assessment tool. 
b. Pain Intensity questions based on the BPI-SF; (worst, least, and average 
pain) will be administered daily ("Daily Pain Survey”). [Participants are also 
asked to note significant changes in medication, mood, activity, sleep or 
stress and report any such changes via email or phone to the study team.  
This is used to assess if there are factors which might impact the pain 
intensity] 
2. Secondary Outcome Measure:   
a. back pain-related quality of life, measured using standard Quality of Life 
(HRQoL SF-12) questionnaire 
b. disability, measured using standard Oswestry Low Back Pain Disability 
questionnaire, and 

 
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c. pain bothersomeness (a measure of pain affect or emotional impact), 
measured using a self-reported back pain bothersomeness scale (0-10 
scale: 0: not at all bothersome; 10: extremely bothersome) (Cherkin et 
al.2016). 
 
AIM 1 - Additional Outcome Measures:  To provide context for the primary and 
secondary outcome measures, several additional data measures will be collected: 
 
3. Detailed assessment of current medications and therapies  
4. Pain Catastrophizing Scale (PCS):  Standardized assessment tool for propensity 
to catastrophize pain.  This data will help us determine if there is a relationship 
between propensity to catastrophize and the efficacy of the therapy. 
5. Fear of Pain Questionnaire:  Standardized assessment tool for fear of pain.  This 
data will help us determine if the therapy affects this fear (the fear-avoidance cycle 
is believed an important driver of pain catastrophizing). 
6. Tampa Scale for Kinesiophobia (TSK, Fear of Movement):  Standardized 
assessment tool for fear of movement.  Fear of movement due to pain is 
considered an important driver of pain catastrophizing (fear-avoidance model).  
Certain modules in VRNT are designed to address this fear of movement; thus, 
this data will provide important context to the how the therapy, and these modules 
in particular, are impacting participants. 
7. PROMIS-SF 43 (anger, sleep, depression, fatigue, sleep,):  Standardized 
assessment tool for assessing the impact of pain on life.  This is important 
additional data on how VRNT might impact participant’s life.   
8. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo):  Standardized 
assessment tool of emotional makeup.  This will provide data on the relationship 
between VRNT and emotional makeup; e.g., does VRNT change these emotional 
states. 
9. General Self-Efficacy Scale (GES):  Standardized assessment of participant’s 
perceived level of self-efficacy.  This data will allow us to determine if VRNT 
improves the sense of self-efficacy, which is one of the intended effects. 
10. Expectations of Treatment Success (pain relief, improvement in function, 
improvement in QoL):  Standardized assessment tool.  This data will be used to 
determine if there is a relationship between expectations and actual treatment 
outcomes. 
11. Patient Global Impression of Change (PGIC):  Standardized tool to assess 
participant’s overall impression of treatment success. 
12. Design Survey: Usability, Effort, Usefulness (10-pt scale):  This survey will provide 
important data on the usability of the product.  It may also provide insight onto 
whether there is a correlation between individual perception of usability and 
treatment outcome. 
13. Life Orientation Test (LOT-R) is a scale that assesses optimism. Optimism has 
recently been shown to be a robust predictor of treatment success in chronic pain 
patients. 
14. -16. The following questionnaires will be administered to assess pain regulation 
and relationship with pain, including emotional regulation strategies (Emotion 

 
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Regulation Questionnaire (ERQ)), mindfulness (Mindful Attention Awareness 
Scale (MAAS)), and pain coping styles (Coping Strategies Questionnaire (CPQ). 
These scales have been used in mind-body treatment studies of pain and they will 
provide data on the effect of VRNT on pain regulation capacity. 
15. The Big-5 SF, a commonly used scale for assessing personality traits, will be 
administered to test whether variable response to treatment across the study 
sample is related to some common personality traits previously shown to be 
associated with pain chronification and pain treatment outcomes.  
 
Data Collection Tools: Items 1-16 will be collected via online Qualtrics surveys.  Except 
Items 1b and 2c (the Daily Pain Survey), the data will be collected during the Surveys 
(Figure 1-2); however, not all questionnaires are completed in each Survey; see 
Procedures for details regarding which questionnaires are administered during each 
Survey session. Items 1b and 2c (Daily Pain Survey) are collected online via Qualtrics 
throughout the study, starting after Survey #1 and ending with Survey #5 for the Therapy 
Group (Survey #8 for Waitlist Group). Research personnel will monitor whether 
participants are completing the Daily Pain Survey through Qualtrics and reach out to 
participants who are not completing it.  
 
Aim 2:  MRI data will be collected on each participant twice.  The first scan will be before 
randomization of participants, and thus before the Therapy Group starts therapy.  The 
second scan is 8 weeks later; for the Therapy Group this is after they complete the 
Therapy Period.  Participants in the Waitlist Group will also be scanned a second time to 
provide comparative data.  MRIs will be conducted according to the policies and 
procedures of Intermountain Neuroimaging Consortium (INC) at the Center for Innovation 
and Creativity in Boulder Colorado. Data collected shall be: 
Pre-MRI Survey:  This survey will be used to assess day-of-scanning sleep, medication 
intake, alcohol consumption, coffee consumption, and demographics.  
 
MRI and physiological data:  Three types of data are collected, and is needed to do the 
analyses of AIM 2: 
a. MRI scan data (1) structural, (2) resting-state, (3) DTI.  These measures 
brain morphometry (1) and functional (2) and structural (3) connectivity 
between brain regions. 
b. Physiological data: Measures of autonomic response (heart rate, SCR, 
breathing) of participants while in the MRI scanner. 
 
OTHER DATA 
In addition to the outcome measures and safety data outlined above, we will be obtaining 
personal medical information from participants about their pain experience.  Finally, we 
will collect qualitative information from participants during the Weekly Calls and a Final 
Debrief Interview. This data will be used to provide context to the study findings and to 
provide input for product improvements. 
 
 
Table 1 – Data Collection (Outcome Measures) 

 
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The listed items are data that will be collected during the study.   
 
 
Name of procedure/instrument/tool 
Purpose (i.e., what data 
is being collected?) 
PRIMARY & SECONDARY OUTCOME MEASURES 
 
Brief Pain Inventory (BPI-SF)  
Measures current degree 
of pain (incl. intensity) and 
symptoms 
Daily Pain Survey 
Measures min, max and 
average daily pain 
intensities throughout 
study, and pain 
bothersomeness (pain 
affect / emotional impact 
of pain)  
Quality of Life (HRQoL SF-12) 
Measures quality of life 
Oswestry Low Back Pain Disability 
Measure of disability, 
social interaction, and 
interference of pain with 
daily activities in back pain 
patients 
ADDITIONAL OUTCOME MEASURES 
 
Detailed assessment of current medications  
Assesses current 
medications and therapies 
Pain Catastrophizing Scale (PCS) 
Measures maladaptive 
coping with pain  
Fear of Pain Questionnaire 
Measures fear of different 
types of pain  
Tampa Scale for Kinesiophobia (TSK, Fear of 
Movement) 
Measures fear of 
potentially pain-causing 
movements  
PROMIS-SF 43 
Assesses sleep, anger, 
depressive symptoms, 
fatigue,  
Survey of Pain Attitudes SF, Emotion subscale 
(SOPA-Emo) 
Measures patient’s 
attitudes and beliefs about 
pain 
General Self-Efficacy Scale (GES) 
Measures perceived 
control in daily activities  
Expectations of Treatment Success 
Measures expectations of 
pain relief, improvement in 
function and improvement 
in quality of life due to 
treatment  
Patient Global Impression of Change (PGIC) 
Measures patient’s 
perception about 
treatment success 

 
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Design Survey 
Measures usability, effort 
needed, and usefulness of 
VRNT 
Life Orientation Test (LOTR) 
Measures dispositional 
optimism 
Emotion Regulation Questionnaire (ERQ)  
Measures emotion 
regulation styles 
Mindful Attention Awareness Scale (MAAS)  
Measures mindful traits 
(acting with awareness, 
present focus, 
responsiveness, social 
awareness) 
Coping Strategies Questionnaire (CPQ)  
Measures pain coping 
styles 
Big-5 short form (Big-5 SF)  
 
Measures personality 
traits  
MRI AND PHYSIOLOGICAL DATA 
 
Pre-MRI Survey 
Assess day-of-scanning 
sleep, medication intake, 
alcohol consumption, 
coffee consumption, and 
demographics 
MRI scan data (1) structural, (2) resting-state, (3) DTI  
Measures brain 
morphometry (1) and 
functional (2) and 
structural (3) connectivity 
between brain regions 
Physiological data  
Measures autonomic 
response (heart rate, 
SCR, breathing) of 
participants while in the 
MRI scanner 
OTHER DATA 
 
Weekly Calls 
Questions about 
adherence / compliance.  
Open-ended questions 
about any problems with 
VR and with therapy (incl. 
technical problems and 
adverse effects) 
Final Debrief Interview  
Open-ended questions 
about participants’ 
experience with VR and 
with therapy 
 
 
 
 
 
 

 
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Sample Size.  We target a sample of N = 60 subjects completing the final surveys,30 per 
group. Since we estimate a ~20% attrition rate, we aim to enroll N = 76 patients into the 
study (N = 38 per group). Pre-screening of participants will take place on Qualtrics via an 
eligibility survey.  
 
Randomization Procedures.  
After the initial baseline information from Phase 1 (Survey #1, Baseline Period, Survey 
#2 and the MRI screen #1) is collected, participants will be randomized into a Therapy 
Group and a Waitlist Group, using a computer-generated random sequence. 
 
Control Group Rationale. 
A Waitlist Group will serve as control group.  The Waitlist Group will not receive a sham 
treatment.  It will provide the same outcome data as the Therapy Group, and it will provide 
two MRI scans pre-/post-waiting period as a comparable to the Therapy Group.  Both the 
Therapy Group and the Waitlist Group will be allowed to continue their normal pain 
treatment (pharmacological and other), the Waitlist Group can serve as a control; that is, 
the VRNT is an adjunct therapy.  Thus, the Waitlist Group serves as a reasonable control 
to the Therapy Group. 
 
Power Analysis. The effect size for VRNT is still unknown. Effect sizes for mirror therapy 
for phantom limb pain have a Cohen’s d = 0.52 (1.64 in subjects without telescoping) to 
0.97 1  whereas (mindfulness) mediation-based treatments for chronic pain have a 
Cohen’s d = 0.27 to 0.45 (Maglione et al. 2018) For a two-group between person test with 
~30 subjects per group, this design will allow us to detect a minimum clinically meaningful 
effect size of d = 0.75 with 80% power at two-tailed α = .05. 
 
Data Analysis.   
AIM 1. Test the efficacy of VRNT in moderate to severe Chronic Back Pain patients. The 
Primary outcome measure is pain (BPI–SF). Secondary Outcome measures are A) 
Disability (Oswestry Low Back Pain Disability), B) Quality of Life (SF-12), and C) Pain 
Bothersomeness. Daily pain scores (e.g. least, worst, average) and pain bothersomeness 
scores will be plotted and assessed for stability and distributional assumptions (normality, 
homoscedasticity, potential outliers), and transformed as appropriate to ensure validity of 
statistical tests. Average pain intensity and bothersomeness baseline and intervention 
phases will be calculated and the primary analysis (Aim 1) will use a General Linear Model 
(GLM) to estimate group differences (VRNT vs. control) in [baseline – post-intervention] 
change scores, controlling for baseline pain, age, and gender, with alpha = 0.05 two-
tailed. The same test will be applied to other outcomes (Table 1). Secondary analyses 
will use the GLM to estimate within-person improvements in the VRNT group, to establish 
that between-group differences are driven by therapeutic improvement from baseline in 
the treatment group, and test whether treatment effects are moderated by age, gender, 
and prior medication use (e.g. opioids, NSAIDS). 
 
AIM 2. Establish brain mechanisms associated with treatment response. Tasks. MRI 
imaging will consist of three types of images: (1) Structural T1 image suitable for 
localization 
of 
functional 
signals, 
voxel-based 
morphometry, 
and 
cortical 

 
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thickness/volumetric analyses; (2) Resting-state functional MRI collected during eyes-
open fixation, widely acquired during large-scale studies, suitable for analysis of 
functional connectivity between brain regions (3) DTI scan suitable for the analysis of 
structural white matter connectivity between brain regions Preprocessing. We will employ 
standard, state-of-the art image preprocessing techniques (SPM12; Wellcome 
Department of Cognitive Neurology, UCL), using procedures detailed in our (i.e. Wager 
Lab) published work (Wager et al. 2011, Woo et al. 2017, Roy et al. 2014), with 
improvements described below. Structural images: inhomogeneity correction, co-
registration to the mean realigned functional image, enhanced generative nonlinear 
normalization using SPM12. Functional images: distortion correction: we use two 
distortion correction images to adjust for nonlinear EPI distortion and field 
inhomogeneities (Calhoun et al. 2017) realignment/motion correction; application of 
normalization parameters, high-pass filtering with an optimized cutoff. Head movement: 
Tolerance for within-run movement is 1 mm displacement/1.5° rotation, achievable in 
~95% of participants. Movement estimates and higher-order transformations (Lund et al. 
2005) will be modeled as nuisance covariates in 1st-level analyses. Gradient artifacts are 
minimized using a multivariate outlier detection method, with outliers (typically < 1% of 
images) modeled as nuisance regressors (Wager et al. 2013). Quality control plots and 
image loss rates are reviewed by study personnel on an ongoing basis and compared 
with quality metrics from other studies. Analysis. Primary analyses will focus on fMRI and 
white matter connectivity related to chronic back pain. Secondary, exploratory analyses 
will identify group differences in post- vs. pre-treatment fMRI and white-matter 
connectivity across the brain using standard GLM analyses. As we will develop 
exploratory brain maps, the following power analysis will apply to the brain mapping: 80% 
power to detect effects of d = 1.22 or larger at P < 0.001 (which often satisfies whole-
brain False Discovery Rate q < 0.05 where large signals exist). We will focus on 
frontostriatal connectivity between ventromedial prefrontal (coordinates [2 52 -2], 8 mm 
sphere) and accumbens (coordinates [10, 12, -8]) areas identified by Baliki et al. 2012. 
as predicting the transition to chronic back pain and shown to mediate effects of cognitive 
regulation on pain (Woo et al. 2017). We will also examine other a priori brain measures 
as they become available.  
 
V. 
FUNDING 
An NIH Small Business Innovation Research (SBIR) grant. 
VI. 
ABOUT THE SUBJECTS  
We anticipate enrolling ~76 participants in order to reach our goal of N = 60 given 
estimated attrition rate of 20% based on previous studies).  Interested applicants will 
receive an email requesting them to complete the online eligibility survey. 
 
To maximize potential enrollment, no specific pharmacological therapies were excluded. 
Participants will provide therapy and dosage data (see Table 1) and must notify the team 

 
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of any changes in medication/treatments. They must agree not to change/add/remove 
any current treatments (unless indicated by their physician) or make large lifestyle 
changes (e.g., diet or exercise) during the study. All subjects who meet eligibility criteria 
for a research study, regardless of race or gender, will be screened for inclusion. The 
inclusion of women and minorities is not expected to affect any of the dependent 
measures of this study, but will, in fact, bolster the generalizability of data obtained. 
Children will not be studied at this time, due to differences in treatment methods. 
Moreover, the study’s length would make obtaining guardian consent challenging.  
 
Inclusion criteria:   
Self-reported: 
1. Participants aged 21 to 70 with Chronic Back Pain.  
2. Chronic Back Pain will be defined according to criteria established by recent NIH 
task force.  Pain duration must be ≥ 3 months, with back pain being an ongoing 
problem for at least half the days of last 6 months; i.e., either pain every day for 
past 3 months, or half or more of the days for past 6+ months.  
3. Subjects must rate pain intensity at ≥ 4/10 on Brief Pain Inventory (average pain 
over the last week).  
4. Participants must also be comfortable and able to communicate via email, text 
message, or phone in English.  Participants must also be comfortable using a 
video-conferencing service such as Zoom to complete the on-line sessions  
 
Exclusion criteria: 
Self-reported:  
1. Applicants, who are pregnant, planning pregnancy, or breastfeeding  
2. Back pain associated with compensation / litigation within 1 year.  
3. Leg pain greater than back pain (suggests neuropathic pain; may be less 
responsive to psychological therapy).  
4. Chronic pain other than  chronic back pain 
5. Diagnoses of schizophrenia, multiple personality dissociative identity disorder. 
6. History of major depressive disorder not controlled with medication or other 
conditions that produce significant cognitive or emotional disability.  
7. History of substance abuse.  
8. Inability to undergo MRI (determined at screening; see XVI: Risks to Participants).  
9. Any clinically significant unstable medical abnormality or acute or chronic disease 
of cardiovascular, gastrointestinal, respiratory (e.g., chronic obstructive pulmonary 
disease), hepatic, or renal systems; including: history of cardiovascular disease or 
issues (e.g., recent heart attack), stroke; brain surgery, or brain tumor; Diabetes; 
cancer (last 12 months); diagnosis of a specific inflammatory disorder: rheumatoid 
arthritis, polymyalgia rheumatica, scleroderma, Lupus; polymyositis; or Cauda 
Equina syndrome.  
10. History of seizure disorder, epilepsy, convulsions, or increased intracranial 
pressure anytime except pediatric febrile seizures 
11. History of vertigo, dizziness, susceptibility to motion sickness 
12. History of head injury within 6 months,  
13. Unexplained, unintended weight loss of ≥ 20 lbs in past year.  

 
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14. Self-reported history of (digital) eye strain or computer vision syndrome. 
15. Unable or unwilling to meet study attendance requirements. 
16. MRI contraindications as determined by MRI safety screen (e.g., pregnancy, metal 
in body, claustrophobia, using the standard screen conducted by the MRI imaging 
facility).  
 
VII. 
VULNERABLE POPULATIONS 
None 
VIII. 
RECRUITMENT METHODS 
Patients will be recruited through two channels: 
 
a. Members of the research team will contact previous back pain study participants from 
the CANLab, who have consented to being re-contacted for future studies.  
Participants who were enrolled in a previous back pain study run through the Cognitive 
and Affective Neuroscience lab and have expressed written consent to be contacted 
for future studies by the lab may also be notified by the study team. The CANLab has 
a recruitment database of back pain patients that the lab’s PI has access to. These 
are patients from a previous study who have consented to being re-contacted for 
future studies.  
b. Advertisement via flyers, electronic bulletin boards, and social media (e.g., Facebook).  
 
 
 
 
 
IX. 
COMPENSATION  
Participants will be paid $200 in cash or check at the conclusion of the study. In the event 
that a participant withdraws partway through the study, they will be paid a prorated rate 
depending on the surveys completed as follows:  
 
Survey #1 
$25 
Survey #2 & MRI #1 
$70 
Subject Population(s) 
Number to be enrolled in each 
group  
Chronic 
back 
pain 
community 
sample 
 
Therapy (VRNT) Group:  38 
Waitlist Group:                 38 
Recruitment methods/materials  
1. Re-contact previous back pain study participants  
2. Physical flyer  
3. Online advertisement  

 
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Survey #3 
$10 
Survey #4 & MRI #2 
$70 
Survey #5 
$25 
Survey #6-8 (Waitlist) 
No compensation 
 
X. 
INFORMED CONSENT  
Following completion of the screening form and passing the screening requirements, 
informed consent will be obtained as follows: (1) participants will be sent an email link to 
an online DocuSign consent form, (2) study staff will schedule a time to call the potential 
participant to conduct consent interview, (3) participant will sign consent (via DocuSign ) 
after the consent interview has occurred. Participants will also be asked to note whether 
the study personnel have permission to re-contact them regarding future studies. 
Coercion and undue influence will be minimized by reminding participants that their 
participation is voluntary, and that the VRNT treatment is not appropriate for everyone.    
 
Re-consent procedure (June 9 amendment): Some participants will need to be re-
consented for the modified procedures with the new consent form (IRB amendment to 
protocol submitted June 9, 2020). Immediately upon approval of the requested changes 
to the protocol, these participants will be sent an email summarizing the changes to the 
protocol and a link to the new online DocuSign consent form.   
Re-consent procedure (June 16 amendment): Some participants will need to be re-
consented for the modified procedures with the new consent form (IRB amendment to 
protocol submitted June 16, 2020). Immediately upon approval of the requested changes 
to the protocol, these participants will be sent an email summarizing the changes to the 
protocol and a link to the new online DocuSign consent form.   
 
 
In accordance to 21 CFR 50.27(a), participants will have a signed copy of the consent 
form in DocuSign. 
 
XI. 
PROCEDURES  
The study Procedures, as experienced by each participant group (Therapy vs. Waitlist), 
are as follows.  Note:  the participant will not actually be assigned to a participant group 
until after Survey #3 & MRI #1.   
 
 
THERAPY GROUP PROCEDURES 
 
Phase 1 
 

 
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After the Consent Form is completed, study personnel will contact participants via their 
preferred contact method (e.g. email / phone; asked in the Eligibility form) to schedule 
their MRI #1 ~2 weeks later.  The MRI’s will be conducted at the Intermountain 
Neuroimaging Consortium (INC) facility, located within Center for Innovation and 
Creativity (CINC).  Participants will also receive an email with instructions for completing 
Survey #1, an explanation of how they are to complete the “Daily Pain Survey”, and an 
overview of upcoming steps in the study. 
 
 
Survey #1 (~ 1 hour). On-line Qualtrics survey. Participants will be sent a link via email. 
Survey #1 includes the following questionnaires 
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire (FOP) 
7. Tampa Scale for Kinesiophobia (TSK) 
8. PROMIS-SF 43 (anger, sleep, depression, fatigue, sleep) 
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 
 
 
Baseline Period (2 weeks). During these two weeks all participants will be asked to 
complete the Daily Pain Survey online via Qualtrics once a day, which takes about 5 
minutes to complete (last thing in evening. The Daily Pain Survey includes pain intensity 
questions (based on BPI-SF), including worst, least, and average pain and current pain 
(each on a 11-point NRS), and pain bothersomeness scale (a 11-point NRS).  Participants 
are also asked to note significant changes in medication, mood, activity, sleep or stress 
and report any such changes via email or phone to the study team. 
 
Survey #2 (~1 hour and 20 mins). At the end of the Baseline Period, all participants will  
complete Survey #2 online via Qualtrics. Survey #2 includes the following questionnaires:  
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire (FOP) 
7. Tampa Scale for Kinesiophobia (TSK) 
8. PROMIS-SF 43  
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 

 
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11. Expectations of Treatment Success (pain relief, improvement in function, 
improvement in QoL) 
12. Life Orientation Test (LOT-R)  
13. Emotion Regulation Questionnaire (ERQ) 
14. Mindful Attention Awareness Scale (MAAS)  
15. Coping Strategies Questionnaire (CPQ) 
 
MRI #1 (~1hour and 30 mins): Participants will have an in-person session at CINC for 
MRI #1. Prior to the MRI, participants will fill out a short survey (‘Pre-MRI Survey’) on a 
computer at CINC and change into scrubs for the scan (30 mins). The MRI scanning will 
last ~1 hour. 
 
MRI session details The participant will undergo 3 MRI scans: (1) a 7-minute structural 
MRI scan, during which the participant can have their eyes open or closed, (2) ~10-minute 
resting-state functional MRI (fMRI) scan, during which the participant is asked to have 
their eyes open and fixated on a plus-sign displayed on the screen in front of them, and 
a (3) ~6-minute Diffusion Tensor Imaging (DTI) scan, during which the participant can 
have their eyes open or closed. While participants are in the MRI scanner, we will also 
monitor their physiological responses (e.g., heart rate, skin conductance, respiration). We 
will collect these measures by using non-invasive sensors, which are not associated with 
any uncomfortable, harmful or painful sensations. 
MRIs will be conducted according to the policies and procedures of Intermountain 
Neuroimaging Consortium at the Center for Innovation and Creativity in Boulder 
Colorado. INC MRI technologists are not trained to read the scans for abnormalities; 
however, should an anomaly be observed, these images will be flagged and read by a 
neurologist or licensed radiologist at the Mind Research Network. Subjects will be notified 
by the INC staff of the results of the radiology report, regardless of the outcome. Subjects 
will also receive a letter from the Mind Research Network that includes the radiology 
report. 
 
All participants will be scheduled for an MRI #2 approximately 8 weeks later (after the 
Therapy Period is completed, see below for details).  
 
Randomization. After MRI #1, participants will be randomized (50/50) to the Therapy and 
Waitlist groups, using a computer-generated random sequence. Randomization is after 
the MRI #1 to avoid potential bias.  This is the point at which participants find out that they 
are in the Therapy Group. 
 
Phase 2 
 
Therapy Period (8 weeks).  Participants assigned to the Therapy Group will begin the 
VRNT protocol.  NOTE:  Therapy Group participants will be asked to maintain their other 
pain treatments (e.g. pharmacological or other therapies), unless otherwise directed by a 
physician; participants will be asked to report major changes.  Participants will be asked 
to continue to maintain their “Daily Pain Survey” (Qualtrics online) throughout the Therapy 
Period. 

 
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VRNT has four components: 1) Education, 2) Treatment Personalization, 3) VRNT 
Practice Session, and 3) “Therapy” Modules.  The Education and Treatment 
Personalization sessions are completed together with a research team member at CINC.  
Participants will be scheduled for one or two (depending on participant availability) in-
person meetings at CINC [Due to changes in the University’s COVID-19 protocols, all 
one-on-one sessions were moved to video conferencing over the course of the study].  
Participants will be given the option to complete the Education session with other 
participants; Treatment Personalization sessions will be done only in private sessions.  
The Therapy Modules are done by the participants at home. 
 
1) Education (~1 hour and 30 mins; via video-conferencing):  Completed via video-call 
service (e.g. Zoom), this session will include a (PowerPoint-based + short Video) 
education of each participant in the science behind chronic pain.  To help reinforce some 
key points and help participants to engage in self-evaluation based on the learnings from 
this session, a voluntary Self-Evaluation will be sent out via Qualtrics  at the end of the 
session. 
 
2) Treatment Personalization (~ 1 hour and 30 mins; via video-conferencing):   In this 
session, certain aspects of the VR therapy are personalized for each participant.  After 
the session, the personalization files will be ported as an “app” onto a smartphone, which 
the participant will later use, together with a mobile VR headset, at home; the mobile VR 
“app” provides the Therapy Modules.   
 
3) In-Person VRNT Practice Session (~ 1 hour and 30 mins; in-person; moved to video-
conferencing):   This session will be in-person at CINC / Zoom call.  Sessions will involve 
only one participant at a time.  A team member will explain how to use the hardware and 
software.  The participant will then get to practice at least three modules, including one of 
the modules from the first week and two more challenging modules. 
 
 
4) “Therapy” Modules (3-15 mins each):  All the Modules are in the VRNT app on the 
mobile VR equipment.  Based on a prescribed schedule (detailed in an accompanying 
Workbook), the participant will select from several therapy modules.  
 
Participants will be given a Workbook which specifies the modules they should complete 
each day; it also provides some additional exercises to be completed in the real world.  
While the Workbook contains instructions on how to use VRNT, participants will also be 
provided with short video tutorials, covering basic navigation of the app and how to 
navigate the more intricate modules.  Participants are asked to use VRNT a minimum of 
once a day for 5 days per week.  Each session lasts between 15 – 30 minutes.  There 
may be days where the session may take longer, based in part on participant interest. 
The VRNT program will encourage participants to explore movement, exercise and 
activities (of increasing challenge) in their regular life that they previously felt they could 
not do.  In this way, the program seeks to incorporate the experiential learnings from 
VRNT into the participant’s life.  However, participants will NOT be asked to perform any 

 
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special physical exercise program; they are merely encouraged to apply their learnings 
from VRNT in the real world. 
 
Weekly Calls (~30 mins each).  Participants will be scheduled for a weekly call. A team 
member will use specific and open-ended questions to check on adherence / compliance, 
and technical problems or side effects.  Participants will be given the option of doing these 
sessions via telephone or video call (e.g. Zoom, Skype). 
 
Survey #3 (~30 mins).  On-line Qualtrics survey. Participants will be sent an email link 4 
weeks into the Therapy Period (mid-way point). Survey #3 includes the following 
questionnaires:  
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Pain Catastrophizing Scale (PCS) 
5. General Self-Efficacy Scale (GES) 
 
Survey #4 (~ 1 hour and 25 mins). At the end of the Therapy Period, participants will 
complete Survey #4 online via Qualtrics. Survey #4 includes the following questionnaires: 
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire 
7. Tampa Scale for Kinesiophobia (TSK, Fear of Movement) 
8. PROMIS-SF 43  
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 
11. Patient Global Impression of Change (PGIC) 
12. Design Survey: Usability, Effort, Usefulness 
13. Life Orientation Test (LOT-R)  
14. Emotion Regulation Questionnaire (ERQ) 
15. Mindful Attention Awareness Scale (MAAS)  
16. Coping Strategies Questionnaire (CPQ) 
 
MRI #2 (~1 hour and 30 mins). At the end of the Therapy Period, participants will have 
an in-person session at CINC for MRI #2. Prior to the MRI, participants will fill out a short 
survey. The MRI procedures are the same as for MRI #1. Prior to scanning, participants 
will complete the short Pre-MRI Survey (minus the demographic questions) and MRI 
Screening Form and change into scrubs for the scan (~ 30 mins).  
 

 
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Debrief call (~45 minutes). A debrief call will be scheduled for the week following the MRI 
#2 session.  In the Debrief call participants will be asked open-ended questions about 
their experience with VRNT. 
 
Phase 3 
 
Follow-Up Period (2 weeks). Participants will be asked to continue the “Daily Pain Survey” 
in Qualtrics. 
 
Survey #5. (~ 1 hour and 25 mins)  On-line Qualtrics survey. At the end of the Follow-Up 
Period participants will be sent an email link. Survey #5 includes the following 
questionnaires:  
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire 
7. Tampa Scale for Kinesiophobia (TSK, Fear of Movement) 
8. PROMIS-SF 43 (anger, sleep, depression, fatigue, sleep, social interaction, pain 
interference) 
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 
11. Patient Global Impression of Change (PGIC) 
12. Life Orientation Test (LOT-R)  
13. Emotion Regulation Questionnaire (ERQ) 
14. Mindful Attention Awareness Scale (MAAS)  
15. Coping Strategies Questionnaire (CPQ) 
16. Big-5 Short Form (Big5-SF) 
 
 
Focus group session (~2 hours, optional). An optional “focus group” session for Therapy 
Group participants will be scheduled in the 2 weeks after the Follow-Up period. Structured 
and open-ended questions will be used to obtain feedback on the product and therapy, 
the perception of how VRNT worked, problems and recommendations. In addition, 
questions will seek context for the quantitative measures, including those related to the 
mechanisms behind VRNT.  Based on state and university guidelines at the time, this 
session may be offered in-person (following appropriate – e.g., social distancing – 
guidelines) or via a video call (e.g. Zoom). 
 
 
WAITLIST GROUP PROCEDURES 
 
Phase 1. Procedures are identical to the Therapy Group. 
 

 
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Phase 2 
 
Waiting Period (8 weeks). Waitlist Group (control) participants will be asked to maintain 
their current pain management protocols, unless otherwise directed by a physician; 
participants will be asked to report major changes. The control is needed to isolate 
treatment effects from the effects of time and any effects associated with simply enrolling 
in a study. No additional therapy or VR app will be provided during the waiting period to 
maintain Waitlist “illusion”, limit workload, and to limit confounding effects. 
 
Survey #3 (~ 30 mins).  On-line Qualtrics surveys. Participants will be sent an email link 
4 weeks into the Waiting Period (mid-way point). Survey #3 includes the following 
questionnaires 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Pain Catastrophizing Scale (PCS) 
5. General Self-Efficacy Scale (GES) 
 
Survey #4 (~1 hour and 10 mins). Same procedures as for the Treatment Group, except 
that the Waitlist Group participants do not complete the PGIC and Design Survey 
questionnaires, as they have not completed the therapy (therefore Survey #4 is 15 mins 
shorter than for the Treatment Group) 
 
MRI #2 (~1 hour and 30 mins): Same procedures as for the Treatment Group.  
 
 
PHASE 3 
 
Follow-Up Period (2 weeks). Participants will be asked to continue the “Daily Pain Survey” 
in Qualtrics.  For the Waitlist Group this period actually serves as a pre-therapy baseline 
period. 
 
Survey #5 (~1 hour and 20 mins).  On-line Qualtrics survey. At the end of the Follow-Up 
Period the Waitlist Group will be sent an email link.  Survey #5 includes the same 
questionnaires as Survey #5 for Treatment Group above, except that Waitlist Group 
participants do not complete the PGIC, as they have not completed the therapy (therefore 
Survey#5 is 5 mins shorter than for Therapy Group).  
 
 
PHASE 4 
 
Waitlist Therapy Treatment.  After completing Survey #5, Waitlist participants are 
scheduled to receive the Educational, Treatment Personalization and VRNT Practice 
session(s), Waitlist participants will then complete the 8-week Therapy Period, all with the 
same protocol as the Therapy Group.  They will maintain their “Daily Pain Surveys” on 
Qualtrics throughout the period and will be scheduled for the 8 Weekly calls. 

 
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HRP-503: Template Protocol 
 
Survey #6.  On-line Qualtrics surveys. Participants will be sent an email link 4 weeks into 
the Therapy Period (mid-way point).  This survey takes roughly 30 minutes to complete. 
Survey #6 Includes: 
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Pain Catastrophizing Scale (PCS) 
5. General Self-Efficacy Scale (GES) 
 
Survey #7. At the end of the Therapy Period, participants complete the Survey #7 online 
via Qualtrics.  Survey #7 includes the following questionnaires, and takes about 1 hour 
and 25 minutes to complete: 
 
1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire 
7. Tampa Scale for Kinesiophobia (TSK, Fear of Movement) 
8. PROMIS-SF 43 (anger, sleep, depression, fatigue, sleep,) 
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 
11. Patient Global Impression of Change (PGIC) 
12. Design Survey: Usability, Effort, Usefulness 
13. Life Orientation Test (LOT-R)  
14. Emotion Regulation Questionnaire (ERQ) 
15. Mindful Attention Awareness Scale (MAAS)  
16. Coping Strategies Questionnaire (CPQ) 
 
Debrief call. During the MRI #2 session, participants will be asked to schedule a 45-minute 
debrief call. In the Debrief call participants will be asked open-ended questions about their 
experience with VRNT.  
 
Equipment Drop-Off. Participants will be asked to schedule a short visit to CINC to return 
the VR equipment (curb-side).  
 
Follow-Up Period (2 weeks). Participants will be asked to continue the “Daily Pain Survey” 
in Qualtrics. 
 
Survey #8.  On-line Qualtrics surveys. At the end of the Follow-Up Period will be sent an 
email link. This survey will take roughly 1 hour and 25 minutes to complete. Survey #8 
Includes: 
 

 
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1. Brief Pain Inventory – Short Form (BPI-SF) 
2. Quality of Life (HRQoL SF-12) 
3. Oswestry Low Back Pain Disability  
4. Detailed assessment of current medications 
5. Pain Catastrophizing Scale (PCS) 
6. Fear of Pain Questionnaire 
7. Tampa Scale for Kinesiophobia (TSK, Fear of Movement) 
8. PROMIS-SF 43 (anger, sleep, depression, fatigue, sleep, social interaction, 
pain interference) 
9. Survey of Pain Attitudes SF, Emotion subscale (SOPA-Emo) 
10. General Self-Efficacy Scale (GES) 
11. Patient Global Impression of Change (PGIC) 
12. Life Orientation Test (LOT-R)  
13. Emotion Regulation Questionnaire (ERQ) 
14. Mindful Attention Awareness Scale (MAAS)  
15. Coping Strategies Questionnaire (CPQ) 
 
 
 
Procedures and time requirements  
 
Visit # 
Procedures/Tools 
Location 
How much time the 
visit will take 
THERAPY GROUP 
  
  
  
  
Survey #1 
(from Home) 
Survey #1 
Questionnaires - 
Qualtrics online 
Online 
1 hour 
Baseline Period - 2 
weeks 
(from Home) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Survey #2 & MRI 
#1 
Survey #2 
Questionnaires - 
Qualtrics online 
Online 
1 hour 20 minutes 
Preparation for 
scanning (MRI 
Screening Form and 
Pre-MRI survey, 
change into scrubs, use 
restroom)  
Center for 
Innovation and 
Creativity (CINC) 
30 minutes 

 
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MRI scan 
CINC 
1 hour 
Therapy Period - 8 
weeks 
1) Education 
Video Call 
1 hour and 30 mins 
2) Treatment 
Personalization 
Video Call 
1 hour and 30 mins 
3) VRNT Practice 
Session 
CINC [Video 
Call] 
1 hour and 30 mins 
4) Therapy Modules:  
min. once a day for 5 
days / week 
Online 
20-39 hours over an 
8-week period (each 
day will require about 
15-30 minutes of 
participation time) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Weekly Calls 
Phone 
30 minutes 
Survey #3 
(from Home) 
Survey #3 
Questionnaires - 
Qualtrics online 
Online 
30 minutes 
Survey #4 & MRI 
#2 
Survey #4 
Questionnaires - 
Qualtrics online 
Online 
1 hour 25 minutes 
Preparation for 
scanning (MRI 
Screening Form and 
Pre-MRI survey, 
change into scrubs, use 
restroom)  
CINC 
30 minutes 
MRI scan 
CINC 
1 hour 
Follow-Up Period - 
2 weeks 
(from Home) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Survey #5 
(from Home) 
Survey #5 
Questionnaires - 
Qualtrics online 
Online 
1 hour 25 minutes 
Final Debrief Interview 
Phone 
45 minutes 

 
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OPTIONAL Focus 
Group 
Focus group questions 
Online 
2 hours 
  
WAITLIST GROUP 
  
  
  
  
Survey #1 
(from Home) 
Survey #1 
Questionnaires - 
Qualtrics online 
Online 
1 hour 
Baseline Period - 2 
weeks 
(from Home) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Survey #2 & MRI 
#1 
Survey #2 
Questionnaires - 
Qualtrics online 
Online 
1 hour 25 minutes 
Preparation for 
scanning (MRI 
Screening Form and 
Pre-MRI survey, 
change into scrubs, use 
restroom)  
Center for 
Innovation and 
Creativity (CINC) 
30 minutes 
MRI scan 
CINC 
1 hour 
Waiting Period - 8 
weeks 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Survey #3 
(from Home) 
Survey #3 
Questionnaires - 
Qualtrics online 
Online 
30 minutes 
Survey #4 & MRI 
#2 
Survey #4 
Questionnaires - 
Qualtrics online 
Online 
1  hour 10 minutes 
Preparation for 
scanning (MRI 
Screening Form and 
Pre-MRI survey, 
change into scrubs, use 
restroom)  
Center for 
Innovation and 
Creativity (CINC) 
30 minutes 
MRI scan 
CINC 
1 hour 
Follow-Up Period 
(Waitlist's pre-
treatment baseline) 
- 2 weeks 
(from Home) 
“Daily Pain Survey” – 
Qualtrics online 
Online 
5 minutes 

 
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HRP-503: Template Protocol 
Survey #5 
(from Home) 
Survey #5 
Questionnaires – 
Qualtrics online 
Online 
1 hour and 20 mins  
Waitlist Group’s 
Therapy Period - 8 
weeks 
1) Education 
Video Call 
1 hour and 30 mins 
2) Treatment 
Personalization 
Video Call 
1 hour and 30 mins 
3) VRNT Practice 
Session 
CINC [Video 
Call] 
1 hour and 30 mins 
4) Therapy Modules:  
min. once a day for 5 
days / week 
Online 
20-39 hours over a 8-
week period (each day 
will require about 15-
45 minutes 
participation time) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Weekly Calls 
Phone 
30 minutes 
Equipment Drop 
Off 
Return VR equipment 
CINC (curb-side) 
10 minutes 
Survey #6 
(from Home) 
Survey #6 
Questionnaires - 
Qualtrics online 
Online 
30 minutes 
Survey #7 
Survey #7 
Questionnaires - 
Qualtrics online 
Online 
1 hour 25 minutes 
Follow-Up Period - 
2 weeks 
(from Home) 
“Daily Pain Survey" - 
Qualtrics online 
Online 
5 minutes 
Survey #8 
(from Home) 
Survey #5 
Questionnaires - 
Qualtrics online 
Online 
1 hour 25 minutes 
Final Debrief Interview 
Phone 
45 minutes 
 
 
XII. 
SPECIMEN MANAGEMENT 
N/A 

 
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XIII. 
DATA MANAGEMENT 
According to HRP-211, the security requirements for this study are Level 2.   
 
Study data will be accessed through authenticated mediums on a need to know basis. 
The study team (key personnel and research staff) will have access to the data. 
 
 
Strict standards of confidentiality will be maintained. Study data will be collected via pen-
and-paper (Debriefing call, weekly calls, MRI screening form), Qualtrics (Survey 
questionnaires), MRI, and VRNT software.  
 
Pen-and-paper data will be  stored in a locked file cabinet in a locked room at CINC.  
 
Qualtrics is a secure, widely used data collection tool managed by CU Boulder. Only CU 
Boulder team members (Dr. Ceko and study RA’s) will have access to the Qualtrics data 
platform. Identifying information will be collected during the online screen, which asks for 
participants’ names, phone numbers, and email addresses. After study completion, this 
information will be removed from the Qualtrics database, permanently de-identifying the 
Qualtrics data. 
 
MRI data will be stored according to standard INC data management procedures. MRI 
images will be housed on a CU Boulder RCserver. Metadata (name and contact 
information) will be entered into the COINS database by study personnel. Each COINS 
entry will receive a unique research subject identifier. This code will be associated with 
the images. A copy of the MRI images will be sent to the Georgia State University for data 
sharing and storage. No identifying information is included in the images. 
 
VRNT data on the Personalized Treatment will be synched periodically via a DropBox 
application with a file accessible only to the team. However, the data will only be encoded 
with the subject identifier number. Only the core team members will have access to a 
written matrix tracking participant name to participant identifier.   
XIV. 
PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF PARTICIPANTS  
Data collection will only occur in private contexts, whether at CINC or the participant’s 
home, in order to ensure privacy of all participants. Additionally, Participants will complete 
the Education session individually, unless they indicate that they would be willing to 
complete it in a group setting. The only other group session are the focus groups, which 
are voluntary. 
 
Any information that identifies individual participants will only be accessible to study 
personnel. Furthermore, participants have the right to refuse to provide any identifying 
information.  
XV. 
WITHDRAWAL OF PARTICIPANTS 

 
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Participants may withdraw voluntarily from a study at any time. Participants may either 
withdraw from a particular session, or request that they be removed entirely from the 
participant pool. Withdrawn participants will have no further data collected from them, and 
there will be no follow up contact with them.  
 
We may withdraw participants from the study if: we learn that they added, changed, or 
stopped any concurrent treatment for their pain (for example, undergoing back surgery 
mid-study); participants’ back pain dramatically worsens and we judge they need more 
intensive treatment than that provided in this study.   
 
Withdrawn subjects will have no further data collected from them, and there will be no 
follow up contact with them. They will be replaced with new participants. 
XVI. 
RISKS TO PARTICIPANTS 
 
VR 
Virtual reality (VR) applications have been known to cause motion sickness or temporary 
headaches.  Exclusion criteria are designed to exclude applicants with high susceptibility 
to motion sickness.  Participants are instructed to only use the VR software while seated 
or lying down. Therefore, we do not anticipate risks associated with movement, standing, 
walking, or falling injury while in the VR environment. The program does encourage 
participants to gradually increase movement and activity in their lives. Participants will be 
asked to check with their physicians before engaging in any major new physical 
movement or activity.  VR applications have also been known to cause headaches in 
people with (digital) eye strain of computer vision syndrome.  The exclusion criteria are 
aimed at excluding such applicants. 
 
MRI Scans 
Subjects may experience nervousness and/or claustrophobia during the MRI. While 
generally safe, it is not known whether an MRI would harm a fetus. 
 
The risks of MRI are: 
• The MRI may cause discomfort due to scanner noise.  
• There may be some discomfort from lying still and in one position for a long time. 
• Peripheral nerve stimulation (PNS/tingling). At sufficient exposure levels, peripheral 
nerve stimulation is perceptible as “tingling” or “tapping” sensations. PNS symptoms 
will usually subside shortly after the scan is completed. 
 
MRI anomalies:  While the images are taken for research purposes, participants will be 
notified should an anomaly of clinical importance be observed, as is standard practice for 
INC/MRN images. 
 
Risk of Suicide 
Chronic pain populations can have a higher risk of suicide.  
 

 
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HRP-503: Template Protocol 
XVII. 
MANAGEMENT OF RISKS 
VR 
A member of the research team will email or text subjects 3 days after receiving treatment 
to enquire about any adverse events. Additionally, participants will be asked to report any 
side effects (e.g., nausea) to the PI immediately, who will evaluate and act as appropriate. 
During the pre-screening, we confirm with each subject that they are comfortable with 
phone, email or text message communication, which is needed for completion of the Daily 
Pain Surveys described above. 
 
 
fMRI Scans 
The MRI-related risks will be managed in the following way. The MRI scan will be 
performed using an MR scanner employing pulse sequences and hardware that have 
been approved by the FDA for human clinical use. The field strength is 3 Tesla and all 
relevant operating characteristics (RF power deposition, rate of change of the field 
gradients, coil design) fall within the limits of FDA guidelines for NMR exposure. 
Participants will be carefully screened to exclude those who may have metal in or on their 
bodies that cannot be removed (e g., bullets, metal filings, body piercings, etc.). MR 
Facility rules strictly forbid staff from entering the magnet room carrying metal objects. 
Additionally,  
• Discomfort from scanner noise will be minimized with high-quality noise-blocking 
earbuds. 
• Discomfort from laying in the scanner will be minimized by making sure the subject is 
lying comfortably with head and neck supported. 
• With regard to PNS, participants are given a squeeze ball to use in case of an 
emergency. They are informed that if they experience PNS related sensations or are 
otherwise uncomfortable, they can alert the MRI technologist via the squeeze ball and 
the technologist will stop the scan immediately.  
• The risk of claustrophobia is minimized by screening subjects for self-reported 
claustrophobia and, providing a mirror to see out, a button to signal distress, and an 
intercom.   
• Pregnant women are excluded to minimize risk to the fetus.  In accordance with 
standard INC procedures, female participants unsure as to whether they are pregnant 
will be given the opportunity to complete a urine pregnancy test immediately before 
the scanning period, and those with a positive result will not be scanned. Alternatively, 
female participants may sign a waiver that they do not believe themselves to be 
pregnant. 
 
 
Risk of Suicide 
If a participant relays thoughts of suicide during any part of the project, the participant will 
be followed up with a clinically trained psychologist, who will provide a list of psychological 
resources, both on the college campus and within the community.  If the psychologist 
forms the impression in the conversation that the participant is experiencing elaborated 
thoughts of suicide (including suicidal plans), a licensed clinical psychologist will be 
contacted immediately.  If he / she is unavailable, the Boulder Community Hospital 

 
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Suicide line will be called. Additional action will be taken to ensure the subject’s personal 
safety as per recommendations made for that specific subject. 
 
 
ADVERSE EVENTS 
In addition to the above risk mitigation procedures, Dr. Marta Čeko will monitor any reports 
of adverse events and be responsible for reporting adverse events to the IRB.  
Participants will be encouraged to report immediately any side-effects via 
phone/text/email.   
 
 
XVIII. POTENTIAL BENEFITS  
Subjects may experience a reduction in back pain and / or an improvement in quality of 
life (e.g. coping) from using the VRNT system. 
 
The benefits to society stem from advancing scientific understanding of 
chronic pain, which imposes a large societal burden.  This study will assess a 
novel virtual reality intervention for treating chronic pain. 
XIX. 
PROVISIONS TO MONITOR THE DATA FOR THE SAFETY OF PARTICIPANTS 
A team member will contact subjects periodically and subjects are encouraged to report 
any issues immediately via phone/text/email.  Any information concerning safety shall be 
reported to the PI’s immediately.   
 
The research team will monitor the weekly reports in order to maintain that participants 
are using the device correctly and responding to surveys. The PI’s will monitor these 
reports and be responsible for reporting adverse events. 
XX. 
MEDICAL CARE AND COMPENSATION FOR INJURY 
N/A 
XXI. 
COST TO PARTICIPANTS 
There will be no cost to participants. Parking at CINC is free. 
XXII. 
DRUG ADMINISTRATION 
N/A 

 
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XXIII. INVESTIGATIONAL DEVICES 
 
VRNT software is a developmental stage Investigational Device subject to regulation by 
the FDA; it is, thus, not available for marketing.   
 
 
During the study, VRNT will not be altered, except as follows: 
 
• Bug Fixes:  necessary software modifications to fix any software bugs interfering with 
the proper functioning of VRNT 
 
XXIV. COLLABORATIVE STUDIES 
CognifiSense team members will be involved in recruitment, participant education and 
the creation of VR representations of pain (“drawing” pain), surveys, follow-ups and 
analysis. 
 
XXV. SHARING OF RESULTS WITH PARTICIPANTS 
There are no plans to share research results with participants.  Participants will be offered 
structural MRI images of their brain immediately after the first scan session.