Home-Based Intervention for Chronic Pain in Adults With Sickle Cell Disease (HIPAS)
Phase: NA
Conditions: Sickle Cell Disease
Sponsor: Emory University

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
Protocol Version: VERSION 9 11/9/2023 
Page 1 of 34 
IRB Form BIO 08102020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                           Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease (HIPAS) 
 
                                                             NCT04906707 
 
   Date: 11/09/2023 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
Protocol Version: VERSION 9 11/9/2023 
Page 2 of 34 
IRB Form BIO 08102020 
PROTOCOL TITLE: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease (HIPAS) 
PRINCIPAL INVESTIGATOR: 
Nadine Matthie, PhD, RN, CNL 
Nell Hodgson Woodruff School of Nursing 
(404) 712-8449 
nadine.matthie@emory.edu 
VERSION: 11/9/2023, version 9 
FUNDING SOURCE: 
Federal Agency/National Institutes of Health 
Sponsor’s Funding ID: 1R21NR019872-01 
Grant’s Office ID/Emory EPEX ID: %58129 
Funding Status: Funded 
REVISION HISTORY 
Revision # 
Version 
Date 
Summary of Changes 
1 
12/15/2020 Revision of the informed consent process to address how 
participants can access an electronic copy of the consent form in 
cases of verbal informed consent 
2 
9/9/2021 
Revision of the recruitment methods to include the use of social 
media and an opt-in/opt-out letter as recruitment strategies, if 
necessary 
3 
3/2/2022 
Revision of the inclusion criteria to broaden the age range and 
revision of compensation to participants to provide an increase in 
the incentives 
4 and 5 
6/22/2022 
Revision of the recruitment methods to include an additional 
7/13/2022 
recruitment site. 
6 
10/28/2022 Decrease in sample size, from 72 to 50, due to recruitment 
challenges. 
Due to the exploratory nature of the intervention (EaseVRx), prior 
estimates of treatment effect sizes for the individual outcomes 
(pain, pain coping, sleep, functional activities of daily living, 
disability, healthcare utilization, and quality of life) were not readily 
available; thus, the original study was not powered for these 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
Protocol Version: VERSION 9 11/9/2023 
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IRB Form BIO 08102020 
individual outcomes. Instead, we focused on identifying the 
minimum detectable effect size at 80% power and 5% significance 
level. Given that this is a pilot study, our primary objective is to 
analyze data with the specific intent of establishing population 
parameters and estimating effect sizes. 
Modified power calculations indicate that with a sample size of 
40, we will have the ability to detect a minimum standardized 
difference (Cohen’s d) of 0.9 with adequate power (80%) at a 5% 
significance level. The reduced sample size will still allow us to 
make meaningful conclusions regarding feasibility and estimation 
of effect sizes. To obtain a final sample size of n = 40, we are 
looking to enroll n = 50 participants to account for a potential 20% 
dropout or non-completion rate. 
8 
5/3/2023 
Revision of the informed consent process to include the option of 
using e-consent for completion of the informed consent form and 
electronic signature of consent by study team members obtaining 
verbal informed consent. 
Revision of data collection procedures to note that study 
activities and collection of data points will be completed 
whenever possible given participants’ underlying condition and 
because this is a pilot study. 
9 
11/9/2023 
Revision of the study protocol to include a projection to enroll n = 
70 – 90 participants, instead of n = 50 participants, to obtain a final 
sample size of n = 40.  
The previous version of the protocol included a projection to enroll 
n = 50 participants, accounting for a potential 20% drop-out or 
non-completion rate, to obtain a final sample size of n = 40. 
However, the observed rate of drop-out or non-completion was 
more than double the potential estimate. Therefore, more 
individuals need to be enrolled to try to achieve a final sample size 
of n = 40.  

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
Protocol Version: VERSION 9 11/9/2023 
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Table of Contents 
1. 
Study Summary.............................................................................................................. 3 
2. 
Objectives… ................................................................................................................... 3 
3. 
Background… ................................................................................................................. 4 
4. 
Study Endpoints… ......................................................................................................... 9 
5. 
Study Intervention/Investigational Agent… .................................................................. 10 
6. 
Procedures Involved .................................................................................................... 12 
7. 
Data and Specimen Banking ......................................................................................... 15 
8. 
Sharing of Results with Participants…........................................................................... 15 
9. 
Study Timelines… ..........................................................................................................15 
10. 
Inclusion and Exclusion Criteria… .................................................................................. 16 
11. 
Vulnerable Populations ................................................................................................. 17 
12. 
Local Number of Participants… ..................................................................................... 17 
13. 
Recruitment Methods ................................................................................................... 17 
14. 
Withdrawal of Participants… ......................................................................................... 18 
15. 
Risks to Participants… ................................................................................................... 18 
16. 
Potential Benefits to Participants… ............................................................................... 21 
17. 
Compensation to Participants… .................................................................................... 22 
18. 
Data Management and Confidentiality ......................................................................... 22 
19. 
Provisions to Monitor the Data to Ensure the Safety of Participants ............................. 24 
20. 
Provisions to Protect the Privacy Interests of Participants… .......................................... 25 
21. 
Economic Burden to Participants… ............................................................................... 26 
22. 
Consent Process… ..........................................................................................................26 
23. 
Setting… ....................................................................................................................... 27 
24. 
Resources Available ...................................................................................................... 27 
25. 
Multi-Site Research when Emory is the Lead Site .......................................................... 27 
26. 
References… ................................................................................................................. 27 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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IRB Form BIO 08102020 
1. Study Summary 
Study Title 
Home-Based Intervention for Chronic Pain in Adults 
with Sickle Cell Disease (HIPAS) 
Study Design 
Multi-site, mixed-methods, exploratory, parallel- 
group RCT 
Primary Objective 
To determine the feasibility, acceptability, and 
preliminary efficacy of using EaseVRx for self- 
management of chronic pain among adults with sickle 
cell disease 
Secondary Objective(s) 
To assess how EaseVRx can be tailored for a target 
audience that predominantly consists of Black 
individuals 
Research 
Intervention(s)/Interactions 
Pain management program (EaseVRx) versus audio 
control 
Study Population 
Black, adult men and women (ages 18–50) with a 
diagnosis of sickle cell disease who experience chronic 
non vaso-occlusive pain 
Sample Size 
40 
Study Duration for 
individual participants 
12 weeks 
Study Specific 
Abbreviations/ Definitions 
Sickle cell disease (SCD) 
Virtual reality (VR) 
EaseVRx: 8-week, skills-based, home, virtual reality 
pain management program 
Funding Source (if any) 
Federal Agency/National Institutes of Health 
2. Objectives 
The purpose of this study is to learn about the chronic pain experience of adults with 
SCD and evaluate a pain management program for future intervention development. 
The specific aims are: 
Aim 1 – To determine the feasibility of using EaseVRx for self-management of chronic 
pain among adults with SCD. 
Aim 2 – To assess the preliminary efficacy of EaseVRx on pain and pain-related 
outcomes among adults with SCD. 
• Hypothesis 1: The preliminary efficacy of EaseVRx among users will include decreased 
pain; improved pain coping, sleep, and functional activities of daily living; decreased 
disability and healthcare utilization, and enhanced QOL. 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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Aim 3 – To assess how EaseVRx can be tailored for a target audience that 
predominantly consists of Black individuals. 
3. Background 
Adults with SCD are an underserved, predominantly Black population1 with high priority, 
unmet needs for chronic pain management. Chronic, non vaso-occlusive pain in SCD is a major 
health problem. This pain is currently defined as ongoing pain that was present, in one or more 
locations, on most days for more than six months.2 It is attributed to factors including avascular 
necrosis of joints, bone infarction, leg ulcers, osteomyelitis, and central and peripheral 
sensitization.2-6 Among adults, 54% report having pain 51% of the time and 29% report pain 
almost daily.3 This pain is associated with negative coping behaviors,7,8 functional disability,9 
poor quality of life (QOL),10 and high healthcare utilization10,11 Chronic pain also contributes to 
sleep disturbances12-14, and anxiety and depression,13,14 which in turn, exacerbate the pain 
burden.12,15 Taken together, these factors contribute to lost productivity, morbidity, and 
mortality.9,16-18 Opioids are typically used to manage chronic pain but their access is limited 
because of the opioid epidemic, they are ineffective, and they are associated with greater pain 
(due to hyperalgesia or sensitization), poorer functional outcomes, and higher healthcare 
utilization than non-users.19-24 Therefore, alternative, non-pharmacological, self-management 
approaches are urgently needed to manage chronic pain in SCD. 
Self-management is important for adults, ages 18–40, with SCD because they experience 
a high incidence of chronic pain and disability due to chronic pain,9,25 and they account for the 
majority of the hospitalizations and readmissions due to pain.26-28  In our preliminary work, 
Black adults with SCD reported the need for better pain self-management strategies and new 
resources to support self-management of pain at home.9,25 Effective chronic pain self- 
management interventions often use cognitive behavioral therapy (CBT), the “gold standard” 
biopsychosocial (BPS) approach.29,30 In adults with SCD, CBT has contributed to more positive 
coping skills, greater self-efficacy in managing pain, less use of pain medication, and an 
alleviation of chronic pain.31 Currently, behavioral interventions like CBT that can address the 
pain self-management needs of adults with SCD are not readily accessible and are not included 
in comprehensive SCD care. Barriers to these types of therapies include socio-economic 
disparities, lack of available local therapists, stigma associated with mental health services, 
lengthy travel and treatment times, and low engagement even when delivered online.32,33 There 
is a need for alternative delivery methods that are more engaging and can be utilized at home. 
Virtual reality (VR) can be a more accessible, scalable, and appealing delivery method. 
The immersive and engaging virtual environment promotes distraction from pain, provides a 
sense of control, and can lead to cortical re-patterning and consequent reduction in pain 
perception.34-38 In chronic pain conditions, such as complex regional pain syndrome, 
fibromyalgia, chronic migraines, musculoskeletal pain, and low back pain, VR has successfully 
resulted in pain reduction.36,37,39,40 In addition, the ability to use VR at home,41 combined with 
the popularity of mobile and gaming technology among young adults with SCD,42-44 suggests 
that VR is a promising delivery platform. AppliedVR’s EaseVRx is a multi-modal, skills-based, 8- 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
Protocol Version: VERSION 9 11/9/2023 
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IRB Form BIO 08102020 
week, VR, mind-body approach to daily management of chronic pain that is designed for home 
use. Similar to in-person integrative pain management programs, EaseVRx provides therapeutic 
information to support participants in learning cognitive and behavior self-management skills, 
and retraining the pain pathways. The program incorporates pain education, pain psychology, 
biofeedback training to control breathing, relaxation based on mindfulness-based stress 
reduction (via 360-degree videos), and distraction via interactive games. Program modules are 
presented in a Netflix-style format. In a RCT of EaseVRx versus audio control in adults with 
chronic low back pain or fibromyalgia (> age 18, n = 97), 76% of the VR users reported no 
nausea or motion sickness and 83% reported high satisfaction ratings.40 VR resulted in 
significant improvement in average pain intensity (p=0.036), pain-related inference with activity 
(p=0.005), sleep (p<0.001), mood (p<0.001), and stress (p=0.003). Symptom improvement, over 
time, was found for each pain variable (p<.001) with stronger results strengthening after two 
weeks. These findings support the feasibility and efficacy of using EaseVRx for chronic pain. 
For adults with SCD, VR therapies may be more efficacious and result in fewer 
complications than opioid therapy. Thus, they can contribute to cost savings for the healthcare 
infrastructure. However, EaseVRx has not been tested in SCD. Moreover, the findings of our 
ongoing systematic review investigating the use and efficacy of VR in chronic pain conditions 
indicate that, to date, there have been no published studies of VR interventions for chronicpain 
management for adults with SCD. In addition, currently available VR pain self-management 
tools are designed for a generic or majority audience. Trials of EaseVRx in SCD are needed to 
evaluate the feasibility and establish the efficacy of using VR-based therapies to manage 
chronic pain in Black adults with SCD. In addition, studies are needed to determine how these 
therapies can be revised to be culturally-tailored for a target audience of predominantly Black 
individuals. This study will address all of these gaps. 
Preliminary data and study models 
In conjunction with the literature, the preliminary work conducted by the PI forms the 
basis for this research. 
Role of self-care in young adults with SCD. Using secondary analysis, we evaluated 
relationships among SCD self-efficacy (perceived ability to function daily and manage SCD 
symptoms), social support, socio-demographics, self-care, and hospital visits for pain crises in 
103 Black, young adults (ages 18-30) with SCD.21 The majority of participants were female 
(61.2%), unemployed or disabled (68%), lived with family (73.8%), and had an average of three 
annual hospital visits for crises. Self-efficacy, social support, and years of education were 
positively associated with self-management. However, only income was associated with 
hospital visits for pain crises. These findings illustrate that characteristics important for 
successful self-management abilities and more proximal outcomes (such as daily pain) may 
better indicate pain self-management than distal measures (such as hospital visits). Participants 
also reported doubts about being able to manage their life from day to day. These findings 
suggest the need for additional support to improve self-management. 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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Examining the chronic pain experience of young adults with sickle cell. Using a 
qualitative design, the PI conducted this study to describe the perception of chronic SCD pain, 
understand self-management strategies used for chronic SCD pain, and complete a needs 
assessment for self-management of chronic SCD pain among adults.25 Study participants were 
recruited from a larger study being conducted to evaluate the effectiveness of a decision aid for 
therapeutic options in SCD. Eighteen adults, ages 21-46 with SCD, completed an individual, 
semi-structured interview during which they responded to demographic questions and 
questions regarding chronic pain in SCD. Of the participants, the majority (n = 10; 55.5%) were 
21–30 years of age (mean 33.5, SD 7.6), female (n = 11; 61.1%), employed at least part-time (n 
= 11; 61.1%), single/never married (n = 13; 72.2%), and had a SCD type of HbSS or sickle cell 
anemia (n = 10; 55.5%). The majority of the participants reported experiencing chronic pain 
daily; yet, they were not receiving specific treatment for this pain. Content analysis of the 
interview transcripts revealed that adults with SCD can differentiate between acute and chronic 
pain. However, they experience challenges in managing pain and chronic pain negatively affects 
their quality of life. They utilize a variety of self-management strategies and seek additional 
interventions for the management of chronic pain that are both beneficial and convenient. 
Findings were used to revise the semi-structured interview guide that is being used in our 
ongoing research and will be used in this study. 
Chronic pain in adults with sickle cell disease. Our ongoing research (NHLBI Diversity 
Supplement, 3U01HL128566-02S1) investigates factors that influence chronic pain among 
Black, young adults (ages 18–40) with SCD9 and explores the acceptability of potential strategies 
for future intervention trials. As an aim of this research, we have begun collecting qualitative 
data regarding patients’ perception of and willingness to try a VR pain management program 
(EaseVRx). In individual interviews, 4 study participants were asked to complete two EaseVRx 
15-minute experiences and provide feedback regarding the program. Participants’ comments 
included: 1) "Because like the way she was speaking to me, it kinda like uplifted me. And then 
like the music and the birds, and I was lookin at the clouds. It was very relaxing, like umm, my 
mind was gettin a massage…Very effective."  2)"I would use that thing every day…I know I 
would use it in the morning and I would definitely use it at night.” 3) “That was cool…I loved 
it…It's very colorful…Umm, and just the scenery…It was just pretty cool to me.” 4)"Umm, it has 
really helpful breathing exercises. It would be effective in calming somebodydown.” 
This study will expand upon the findings of this preliminary work. It represents the first 
essential step in developing a culturally-tailored, non-pharmacological, chronic pain self- 
management intervention for Black adults with SCD. Study findings will guide possible 
modification of EaseVRx or development of a novel program to meet the needs and 
preferences of Black, young adults with SCD. We will then conduct a larger RCT of this program 
to test its efficacy in reducing the disease burden of SCD and the associated costs to the 
healthcare system. 
Study models. The Technology Acceptance Model (TAM), the Capability, Opportunity, 
Motivation-Behavior (COM-B) system of the Behavior Change Wheel, and the Integrate, Design, 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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Assess, and Share (IDEAS) framework will guide this research. The TAM is a framework for 
understanding user’s adoption and use of technology.45,46 According to the model, an 
individual’s intent to use and actual use of technology are based on perceptions of the 
technology’s usefulness and ease of use. These perceptions are mediated by external variables 
such as individual differences, system characteristics, social influences, and facilitating 
conditions. This approach will be used to guide our assessment of feasibility in this study. 
Figure 1. Technology Acceptance Model45 
The COM-B system of the Behavior Change Wheel suggests that behavior change interventions 
work by addressing one or more of these significant components: capability (physical and 
psychological), opportunity (physical and social), and motivation (reflective and automatic 
processes).47 These components interact to generate behavior which, in turn, influences these 
components. EaseVRx addresses all three components in the COM-B system by including 
elements of education, persuasion, training, modelling, and enablement. 
Figure 2. The Behavior Change Wheel47 
Figure 3. The COM-B system47 
The IDEAS framework integrates behavioral theory, design thinking, and evaluation and 
dissemination to better guide the development of digital health interventions for changing 
behavior.48 The framework consists of 10 phases that are organized into four overarching 
categories: integrate insights from users and theory, design iteratively and rapidly with user 
feedback, assess rigorously, and share intervention and findings. The IDEAS framework, COM-B 
system, and TAM will be integrated into the methods used for tailoring EaseVRx. 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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Figure 4. The IDEAS Framework48 
Significance, Innovation, and Contribution to Science 
This study is the first RCT that investigates a VR, biopsychosocial (BPS) intervention for 
self-management of chronic pain in Black adults with SCD. While most VR studies have primarily 
focused on distraction or physical rehabilitation, this investigation will also focus on VR’s 
immersive effects, pain management education, and the acquisition of behavioral, pain self- 
management skills that can be used to cope with pain. We offer a non-pharmacological 
approach to chronic pain self-management that is scalable, associated with a lower risk of side 
effects than opioids, and can be implemented into routine SCD care to reduce pharmacological 
treatment and healthcare utilization. This work will advance current research by helping to 
address barriers to the success of behavioral therapies such as availability, accessibility, 
acceptability, and adherence. The proposed research also involves the development of a 
mobile, culturally-tailored, pain self-management approach for adults with SCD; thus, it 
addresses unmet needs. Overall, this work has potential to be high impact given the high pain 
burden associated with SCD, the existing health disparities in comprehensive pain 
management, and the lack of behavioral interventions that are accessible athome. 
This study has the potential to: 1) offer an evidence-based, patient-centered, and 
outcome-driven self-management strategy that can be used long-term; and 2) advance 
scientific knowledge by influencing the broader fields of SCD, pain, and technology. Specifically, 
the proposed study will address gaps in the prior SCD research including: 1) the feasibility and 
efficacy of utilizing a VR, BPS approach for home self-management of chronic pain; 2) patients’ 
goals, needs, and preferences for chronic pain self-management interventions; 3) culturally- 
tailored and disease-specific approaches for self-management of chronic pain; and 4) critical 
elements necessary for developing technology-assisted home-based interventions. Study 
findings will inform the development of a SCD-specific, non-pharmacological, home self- 
management intervention for chronic pain that can be used as an adjunct to standard SCD care. 
Therefore, the proposed project aligns with the priorities of the National Institute of Nursing 
Research,49 National Heart, Lung, and Blood Institute,50 and the national pain strategy goal51 to 
provide effective approaches for self-management of pain in order to decrease the pain 
burden. Knowledge gained from this work can be applied to other chronic pain conditions and 
to other applications of VR in the home environment. 

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4. Study Endpoints 
Aim 1 – To determine the feasibility of using EaseVRx for self-management of chronic 
pain among adults with SCD. 
Primary feasibility measures will include enrollment and randomization, 
engagement, study retention, satisfaction, and safety. Secondary feasibility measures 
related to participants’ satisfaction will include program fit with daily activities, barriers 
to use, and areas of program confusion or misuse. We will estimate the following 
parameters to determine whether the intervention shows promise for further 
investigations to determine its efficacy: 1) enrollment and randomization; 2) dropout or 
non-completion rate; 3) completion rate of baseline, mid-treatment, and post- 
treatment assessments; 4) completion rate of weekly VR modules and daily self-report 
assessments; 5) participant engagement and satisfaction; 6) rate of adverse effects 
(primary safety endpoint); and 7) participants’ perceptions of the content, delivery, and 
tailoring required. Data collection methods will include program usage statistics 
(automatically recorded by the VR program), completion of study assessments, and 
qualitative sessions to collect subjective data. EaseVRx usage data will be surveyed 
monthly for the duration of the intervention. 
Aim 2 – To assess the preliminary efficacy of EaseVRx on pain and pain-related 
outcomes among adults with SCD. 
Outcomes of preliminary efficacy are pain, pain coping, sleep, functional 
activities of daily living, disability, healthcare utilization, and QOL. Pain coping outcomes 
are pain catastrophizing, chronic pain acceptance, chronic pain self-efficacy, health 
literacy, executive function, anxiety, depression, and social support. The pre-specified 
primary outcome is pain coping, and the primary measure of pain coping is pain 
catastrophizing. Data collection methods will include (also see the Schedule of 
Activities): 
Demographics questionnaire 
Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-MeSM) SCD 
Medical History Checklist52-54 
Medical record data collection form 
Pain diary 
Chronic Pain Grade Questionnaire55 
Pain Catastrophizing Scale56,57 
Chronic Pain Acceptance Questionnaire58 
Chronic Pain Self-Efficacy Scale59 
BRIEF Health Literacy ScreeningTool60,61 
Behavior Rating Inventory of Executive Function ®–Adult Version (BRIEF-A)62,63 
PROMIS® Emotional Distress – Anxiety64 
PROMIS® Emotional Distress – Depression64 
Social Support Questionnaire65 

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ASCQ-MeSM Short Forms: Sleep Impact, Pain, Pain Episodes, Emotional Distress, Social 
Functioning, and Stiffness52-54 
Questionnaire to Screen for Cybersickness or Digital Motion Sickness 
Virtual Reality Sickness Questionnaire66,67 
• Hypothesis 1: The preliminary efficacy of EaseVRx among users will include 
decreased pain; improved pain coping, sleep, and functional activities of daily 
living; decreased disability and healthcare utilization, and enhancedQOL. 
Aim 3 – To assess how EaseVRx can be tailored for a target audience that 
predominantly consists of Black individuals. 
We will use a semi-structured interview guide to conduct qualitative sessions 
that will be audio-recorded. Questions will be developed to: 1) assess participants’ 
technology usage and attitudes; 2) assess participants’ satisfaction with the program 
(usefulness and ease of use, favorable and unfavorable elements), program fit with daily 
activities, barriers to use, and areas of program confusion or misuse; 3) explore 
participants’ goals, needs, and preferences for chronic pain self-management 
interventions; 4) understand participants’ perceptions of the cultural appropriateness of 
the program content; 5) identify how participants would revise the program to increase 
its acceptability and usefulness for Black adults with SCD; and 6) assess self- 
management strategies currently used for chronic pain and how these strategies can be 
integrated into a pain program. 
Potential strategies for tailoring the program to improve its cultural sensitivity 
and effectiveness include: 1) working with stakeholders (Black adults with SCD and their 
families and/or caregivers, SCD providers, and SCD community based organizations) to 
develop program content; 2) facilitating coping strategies often used among Black 
individuals by incorporating family and preferred music, addressing spiritual/religious 
needs, and offering the opportunity for social support; 3) replacing the generic guided 
relaxation modules with our own tailored versions, and replacing images of individuals 
and scenery with those selected by stakeholders as being more relevant to the 
population; 4) including SCD-specific content (such as the education on types of pain, 
personal stories and testimonials, and strategies for improving the quality of patient- 
provider relationships; and 5) addressing culturally sensitive concerns such as an 
emphasis on empowerment, recognition of stress related to ethnic minority status and 
socio-economic status, awareness of stigma attached to psychological therapy, and 
possible mistrust of research. 
5. Study Intervention/Investigational Agent 
This study will involve an evaluation of EaseVRx (AppliedVR; Los Angeles, CA) – a 
commercially available pain management program/wellness application. EaseVRx is a multi- 
modal, skills-based, 8-week, VR, mind-body approach to daily management of chronic pain 
that is designed for home use to be worn over the eyes. Similar to in-person integrative 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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pain management programs, EaseVRx provides therapeutic information to support 
participants in learning cognitive and behavior self-management skills, and retraining 
the pain pathways. The program incorporates pain education, pain psychology, 
biofeedback training to control breathing, relaxation based on mindfulness-based stress 
reduction (via 360-degree videos), and distraction via interactive games. Program 
modules are presented in a Netflix-style format. The EaseVRx program focuses on 
acquisition of self-management skills, such as relaxation, mindfulness, and meditation 
techniques, that are intended to be used by patients after the end of the program to 
cope with pain. All program content is mapped to a therapeutically designed curriculum 
with weekly themes. The content is ordered to support the clinical and engagement 
goals of the program. However, participants can return to experiences as desired, and 
we will track the usage data. The core themes that are infused into the curriculum are: 
acceptance, attention shifting, awareness, rehabilitation, self-compassion, healthy 
movement, deep relaxation, visualization, knowledge of pain, distraction, and 
immersive enjoyment. 
Participants will be randomized 1:1 to receive either EaseVRx or control. Participants will 
receive study materials and instructions for home use before being followed prospectively for 
8-weeks with follow-up at 12 weeks. Each week, participants in the VR group will be asked to 
complete 7 assigned modules, averaging 5 minutes in duration and ranging from 2 to 16 
minutes in duration, for a total of 56 modules across the program. The order of the modules is 
fixed but participants can repeat modules as desired. Participants in the control group will be 
asked to use the audio only version of EaseVRx, which excludes references to visual content, to 
complete 7 sessions weekly. They will receive an electronic link to the recordings on 
SoundCloud (a music streaming platform) where they can choose to stream or download the 
audio recordings on their smartphone, laptop, or desktop computer. 
In this study, we will utilize 
an all-in-one, non-tethered VR 
headset (see Figure 5) that is pre- 
loaded with EaseVRx and isdesigned 
for home use. The goal is to obtain a 
total of approximately 20 headsets 
for use by approximately 25 
participants so headsets may be 
used twice. These headsets will be 
stored at the locked PI’s office and 
managed only by 
authorized investigators until 
provided to participants for use. 
Figure 5. Pico G24K Headset with 
AppliedVR Breathing Amplifier 

Protocol Title: Home-Based Intervention for Chronic Pain in Adults with Sickle Cell Disease 
(HIPAS) 
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Participants in the VR group will receive a headset in person or via shipment. They will 
receive education, via AppliedVR onboarding materials such as detailed instructional 
manuals, to ensure safe and comfortable device use at home. Access to technical 
support (telephone and email) will also be provided. After the 8-week home use period, 
the headset will be retrieved from the participants (in person or via shipment) and 
cleaned according to manufacturer and department sanitary protocols before being 
provided to subsequent participants for use. 
6. Procedures Involved 
Study Design 
We will conduct a multi-site, mixed-methods, exploratory, parallel-group RCT of 
EaseVRx versus audio control, engaging a total of 40 Black men and women (ages 18– 
50) with SCD to: 1) determine the feasibility of using EaseVRx for self-management of 
chronic pain; 2) assess the preliminary efficacy of EaseVRx on pain and pain-related 
outcomes; and 3) assess how EaseVRx can be tailored for a target audience that 
predominantly consists of Black individuals. To obtain a final sample size of n = 40, we 
will enroll n = 70–90 to account for dropout or non-completion. Using quantitative and 
qualitative sources, data collection will occur at baseline, mid-treatment (week 4), and 
post-treatment (week 8) and follow-up (week 12). 
Procedures for Participants 
After screening patients for eligibility using the inclusion and exclusion criteria, the 
project coordinator will describe the study to and seek participation from eligible individuals. 
Participants will be informed that the purpose of the study is to test a pain management 
intervention that will be delivered in two different ways, but their group allocation will not be 
revealed. The study conditions will be presented as adjuncts to standard care and there will be 
no restriction on using other pain management methods. After patients provide written, 
informed consent or verbal informed consent, they will complete baseline study 
questionnaires. Once enrolled, participants may self-withdraw at any time, or they may be 
withdrawn if they fail to or are unable to comply with study procedures. In that case, 
recruitment will resume and continue until the target number of participants is reached. 
After completing baseline questionnaires, participants will be randomized 1:1 to receive 
either EaseVRx or control. Only individuals meeting the eligibility criteria for VR will be assigned 
to the VR group. Participants will receive study materials and instructions for home use before 
being followed prospectively for 8-weeks with follow-up at 12 weeks. Participants in the VR 
group will receive an all-in-one, non-tethered VR headset (Pico G24K headset with AppliedVR 
breathing amplifier) that is pre-loaded with EaseVRx. They will receive education and hands-on 
experience with the VR headset to ensure safe and comfortable device use at home. Access to 
technical support will also be provided. Each week, participants will be asked to complete 7 
assigned modules, averaging 5 minutes in duration and ranging from 2 to 16 minutes in 

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duration, for a total of 56 modules across the program. The order of the modules is fixed but 
participants can repeat modules as desired. Participants in the control group will be asked to 
use the audio only version of EaseVRx, which excludes references to visual content, to complete 
7 sessions weekly. They will receive an electronic link to the recordings on SoundCloud (a music 
streaming platform) where they can choose to stream or download the audio recordings on 
their smartphone, laptop, or desktop computer. 
After the treatment period, we will retrieve study materials and conduct the qualitative 
sessions. Of the participants, we will randomly select approximately 50% (n = 10) from the VR 
group and approximately 50% (n = 10) from the control group for the qualitative sessions to 
learn about participants experiences with the treatment program and preferences for pain 
coping strategies. We may conduct individual interviews in participants’ homes or focus groups 
sessions in a private area of the sickle cell clinic or research office, or may utilize remote options 
if necessary or if requested by participants. 
Data Collection Procedures 
Using quantitative and qualitative sources, data collection will occur at baseline, daily, 
mid-treatment (week 4), and post-treatment (week 8 and follow-up at week 12). Quantitative 
sources will include survey instruments, a daily pain diary, and electronic medical record 
review. Qualitative sources will include individual, semi-structured interviews or focus group 
sessions. Participants’ electronic medical records will be reviewed, concurrently with data 
collection, for demographics, medical history, clinical data, analgesic and non-analgesic 
medications, and healthcare utilization. After group allocation at baseline, research activities 
will be conducted remotely in an effort to conceal treatment allocation. 
Given the nature of sickle cell disease and individual disease experiences, we 
anticipate that participants may not be able to complete all study activities or provide data at 
all time points throughout the study. Because this is a pilot study, study activities and 
collection of data points will be completed whenever possible. 

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Study Schema 

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Study Measures and Schedule of Activities 
The valid and reliable survey instruments that will be used to collect study data are 
described in Table 1. All data will be collected via direct entry into REDCap or another online 
data management system that can be accessed using a computer or smartphone. Participants 
will receive a link to complete the electronic surveys and pain diary after baseline data 
collection. 
Table 1. Study Measures and Schedule of Activities 
Study Outcomes 
Measures (see attached documents) 
Data Collection (*W = Week) 
Baseline 
Daily 
(Day 1 
– 56) 
W4 
(Day 
28) 
W8 
(Day 
56) 
W12 
(Day 84, 
Follow- 
up) 
Demographics 
Demographics questionnaire 
x 
Adult Sickle Cell Quality of Life Measurement 
Information System (ASCQ-MeSM) SCD Medical 
History Checklist 
x 
Medical record data collection form 
x 
Pain and self-management 
of pain 
Pain diary 
x 
x 
x 
x 
x 
Pain and disability 
Chronic Pain Grade Questionnaire 
x 
x 
x 
x 
Pain catastrophizing 
Pain Catastrophizing Scale 
x 
x 
x 
x 
Chronic pain acceptance 
Chronic Pain Acceptance Questionnaire 
x 
x 
x 
x 
Chronic pain self-efficacy 
Chronic Pain Self-Efficacy Scale 
x 
x 
x 
x 
Health literacy 
BRIEF Health Literacy Screening Tool 
x 
x 
x 
x 
Executive function 
Behavior Rating Inventory of Executive 
Function ®–Adult Version (BRIEF-A) 
x 
x 
x 
x 
Anxiety 
PROMIS® Emotional Distress - Anxiety 
x 
x 
x 
x 
Depression 
PROMIS® Emotional Distress - Depression 
x 
x 
x 
x 
Social support 
Social Support Questionnaire 
x 
x 
x 
x 
Sleep 
ASCQ-MeSM Sleep Impact Short Form 
x 
x 
x 
x 
Functional activities of 
daily living 
ASCQ-MeSM Pain Short Form 
x 
x 
x 
x 
Quality of life 
ASCQ-MeSM Short Forms: Pain Episodes, 
Emotional Distress, Social Functioning, Stiffness 
x 
x 
x 
x 
Screening prior to 
treatment 
Questionnaire to Screen for Cybersickness or 
Digital Motion Sickness 
x 
Virtual Reality Sickness Questionnaire 
x 
x 
x 
Participant engagement 
and acceptability 
Program usage statistics (automatically 
recorded by the VR program) and completion 
of study questionnaires 
x 
x 
x 
Study retention 
Program usage statistics (automatically 
recorded by the VR program) and completion 
of study questionnaires 
x 
x 
x 
x 
x 
Participant satisfaction, 
and participant needs and 
preferences for tailoring 
the program 
Semi-structured interview guide for qualitative 
sessions 
x 

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7. Data and Specimen Banking 
Not applicable 
8. Sharing of Results with Participants 
In general, individual study results will not be shared with participants. If we find 
something of urgent medical importance to participants, we will inform them, although 
we expect that this will be a very rare occurrence. There may be side effects from the 
study program or procedures that are not known at this time. It is possible that we may 
learn something new during the study about the risks of being in it. If this happens, we 
will contact participants by telephone to inform them of the finding, provide 
educational information regarding the finding, and if required, instruct them on 
following up with a primary care provider or seeking care from another clinician or 
specialist. After informing participants of any new findings, they can decide whether to 
continue to be in the study or not. Participants may be asked to sign a new consent form 
that includes the new information if they decide to remain in the study. In the event of 
any study changes or the need for remote consent, study staff will contact participants 
via telephone or Zoom (audio only), and they will be asked to provide verbal informed 
consent after the consent discussion takes place. If participants request a copy of the 
revised consent form, then they will be emailed a link to the online consent form in 
REDCap. The email will not contain any information related to the participant’s 
condition. 
The research team is committed to the open and timely dissemination of research 
findings. We will adhere to policies regarding dissemination of information from the proposed 
study. The proposed study will be registered at ClinicalTrials.gov after the notice of award is 
received. As outlined in the NIH Policy on the Dissemination of NIH-Funded Clinical Trial 
Information, study results will be submitted to ClinicaTrials.gov no later than 12 months after 
study completion. In addition, a statement related to posting of clinical trial information at 
ClinicalTrials.gov will be included in the informed consent document. We will also adhere to 
Emory University’s internal policy to ensure that clinical trials registration and results reporting 
occur in compliance with policy requirements. 
De-identified study data may be placed into public databases where, in addition to 
having no direct identifiers, researchers will need to sign data use agreements before accessing 
the data. De-identified findings may also be posted on the project website. This can provide a 
forum for obtaining feedback from research participants and their family members or 
caregivers, healthcare providers, and visitors such as professionals and non-professionals. In 
addition, we will share study findings in accordance with the NIH policy. Electronic copies of 
publications arising from the proposed study will be deposited in PubMed Central with proper 
tagging of data to ensure online discoverability and accessibility. 
9. Study Timelines 

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• 
Enrolled individuals will participate in this study for 8 weeks, with follow-up at 12 
weeks. 
• 
We anticipate enrolling all participants within the first six months of the study. 
• 
We estimate a two-year study period for completion of all study activities. 
10. Inclusion and Exclusion Criteria 
Inclusion Criteria 
Black adults, ages 18–50 years; diagnosis of SCD; chronic non vaso-occlusive pain 
experienced > 3 days per week on average for > 6 months; ability to wear a VR head- 
mounted display and move head in cervical rotation, extension, and flexion; sufficient 
fine motor control to operate VR equipment such as a controller; and ability to read, 
write, and understand English. 
Exclusion Criteria 
1. Conditions: Co-morbidities that may influence pain perception; diagnosis of epilepsy 
or susceptibility to seizures, migraines, or other neurological disorders that may prevent 
VR use, and/or other medical conditions due to which individuals are predisposed to 
nausea and dizziness; susceptibility to claustrophobia, motion sickness or cybersickness 
(digital motion sickness); history of blackouts; hypersensitivity to flashing lights or 
motion; lack of stereoscopic vision; severe visual or hearing impairment; inability to 
operate VR equipment (such as inability to turn head or use hands to operate external 
controller); and/or injury to the eyes, face, head, or neck that prevents comfortable VR 
use. 
2. Other exclusions: Medical instability as determined by healthcare providers at the 
study site; significant motor impairment; surgery within the last three months; planning 
to start a new pain management strategy (such as medication, physiotherapy, 
acupuncture, or cognitive behavioral therapy) in the next three months; history of major 
psychiatric disorder (such as schizophrenia or bipolar disorder) not controlled with 
medication or behavioral factors that would interfere with study procedures; alcohol or 
substance dependence, heart conditions, or the presence of implanted medical devices 
(such as cardiac pacemakers) as noted in the electronic health record; cognitive or 
developmental disabilities; active suicidal ideation; inability to read, write, or 
understand English; pregnancy; and/or plans for vacation in the next threemonths. 
This study will not include any of these special populations: 
• Adults unable to consent 
• Individuals who are not yet adults (infants, children, teenagers) 
• Pregnant women 
• Prisoners 

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Community Participation 
Adults with SCD are the target community for this study. Our preliminary and ongoing 
studies have been aimed at evaluating the chronic pain experience among adults with SCD and 
assessing their needs, goals, and preferences for future intervention studies such as this study. 
Therefore, the needs, goals, and preferences of adults with SCD have been incorporated in the 
design of this study of adults with SCD. De-identified study findings may be posted on the 
project website. This can provide a forum for obtaining feedback from the SCD community, 
which includes research participants and their family members or caregivers, healthcare 
providers, and visitors such as professionals and non-professionals. In addition, dissemination 
of results from this study will occur via publications and presentations to the SCD community 
at national and international professional conferences. Electronic copies of publications arising 
from the proposed study will be deposited in PubMed Central with proper tagging of data to 
ensure online discoverability and accessibility. 
11. Vulnerable Populations 
Not applicable 
12. Local Number of Participants 
We anticipate accruing a total of 40 participants locally to achieve a total of 50 
participants from both recruitment sites. To obtain a final sample size of n = 40, we will 
enroll n = 70–90 to account for dropout or non-completion. We expect to screen 
approximately 144 individuals to achieve a total accrual of 40 participants. 
13. Recruitment Methods 
After obtaining approvals, active and passive recruitment for this study will take 
place at the Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital 
(Grady) in Atlanta, Georgia and the James R. Clark Sickle Cell Memorial Foundation (SC 
Memorial Foundation) in Columbia, South Carolina. Active recruitment by the project 
coordinator will involve the weekly screening for eligibility and enrollment of adults 
who receive care in the sickle cell clinic at Grady and who are served by the SC 
Memorial Foundation. Potential participants will be identified and screened for 
eligibility, using the inclusion and exclusion criteria, by conducting an initial review of 
medical records or obtaining patient report. Active recruitment may also occur through 
healthcare providers and community health workers who inform potential participants 
about the study, either in person or via mailed opt-in/opt-out letters, if necessary (see 
attached document), and provide them with contact information for the project 
coordinator or principal investigator (PI). Passive recruitment will occur via the use of 
flyers placed at the sickle cell clinic and SC Memorial Foundation to inform potential 
participants about the study. If necessary, these flyers may also be published on social 

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media including Instagram, Facebook, and Twitter or via a website developed 
specifically for the study. Interested individuals will be invited to contact the program 
coordinator or PI, using the contact information provided on the flyers (see attached 
document), for further information. In the event of any enrollment shortfalls, we will 
do the following to achieve recruitment goals: consider loosening the exclusion criteria, 
expand the study to an additional sickle cell clinic, utilize area resources to increase the 
efficiency of participant enrollment, and/or extend the recruitment period. 
The James R. Clark Sickle Cell Memorial Foundation (SC Memorial Foundation) is 
not engaged in this research. The Foundation will serve as a community-based, 
recruitment site through which potential participants will be contacted and informed 
about the study. Emory study staff will coordinate, in person or remotely, recruitment 
and participant onboarding activities for potential participants identified through the 
SC Memorial Foundation. 
The participant burden is estimated to be 45 minutes at each time point for 
surveys, 2 hours weekly of intervention for 8 weeks, and 1 hour for qualitative sessions. 
Participants will receive $50 after baseline, $50 after each 4-week study period ($150 in 
total), and $50 after the qualitative sessions. 
14. Withdrawal of Participants 
Data collection will be monitored daily by the study team. Participants will be 
sent a reminder text or email if they do not submit data after 4 days. If no response is 
received after 2 days, a team member will conduct a telephone call. We will use a 
maximum of 3 attempts to contact participants. If 2 weeks have passed since last data 
submission and contact attempts have been unsuccessful, the participant will be 
considered lost to follow-up and will be withdrawn from the study. Before making this 
determination, we will try to regain contact with the participant (via 3 telephone calls 
and, if necessary, a certified letter mailed to the participant’s last known address). These 
attempts will be documented in the participant’s study file. 
We may conclude an individual’s participation in this study without their consent for any 
reason, especially if we believe it is in their best interest or if they were to object to any future 
changes that may be made in the study plan. Expected reasons for conclusion of participation may 
include: 
• Experiencing any symptoms of cybersickness or digital motion sickness (such as dizziness, 
lightheadedness, issues with balance, nausea, and/or vomiting) during or afterexposureto 
VR 
• Experiencing severe mentaldistress 
If participants do not finish any portion of the study, then they will be 
compensated for the portion(s) they have completed and will no longer have their data 
collected after they have withdrawn from the study. Data that were already collected 
may still be used for this study as we try to understand pain in individuals with sickle cell 
and develop interventions. If participants would like us to discontinue use of their data 
after they withdraw from the study, then they will contact the principal investigator, at 

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the mailing address provided, with a written request. Once we receive the written 
request, their data will be destroyed. 
15. Risks to Participants 
Potential Risks 
This study involves minimal risk, if any. Exposure to VR may result in an infrequent 
physical risk of cybersickness or digital motion sickness. In addition, we will solicit information 
regarding participants' pain and disease experiences. Therefore, there is a potential, likely, 
infrequent psychological risk because discussion of these experiences might result in emotional 
distress and/or embarrassment to the participants. There may also be rare, social risks in that 
there may be social harm (i.e., stigmatization) to the participant and larger community of individuals 
with SCD. A breach of confidentiality may result in social consequences such as being perceived 
negatively by healthcare providers, family members, or employers. Economic consequences may 
also arise if individuals need to choose an alternate healthcare provider because of a breach of 
confidentiality. This alternate healthcare provider may be in another county or state. Accordingly, 
the participant may incur costs for transportation and/or care. 
Procedures to Reduce Risks 
Study recruitment and data collection will occur in person, in a private area of 
the SCD clinic, SC Foundation, or research center, or remotely while participants are at 
home. All potential participants will be screened for eligibility using the inclusion and 
exclusion criteria. Eligible participants will receive information about the study, and will 
be asked to complete an informed consent, or a verbal informed consent, and a Health 
Insurance Portable and Accountability Act (HIPAA) authorization form. The informed 
consent document states that participants may choose to not answer any question or 
may end their participation in the study at any time. During the interviews or focus 
group sessions, participants will be reminded that their participation is voluntary and 
that they may stop at any time if they are uncomfortable with any questions. 
Prior to treatment, we will ask potential participants screening questions, using 
the Questionnaire to Screen for Cybersickness or Digital Motion Sickness, to determine 
whether they have had or may have any of these issues. If so, they will not be 
considered eligible for participating in the VR group only. If they are considered eligible 
for the VR group (provided no affirmative responses to the screening questions), then 
participants will remotely complete the Virtual Reality Sickness Questionnaire before 
each use of the VR program. Only individuals without severe symptoms, as reflected on 
the questionnaire, will move forward with VR use. These individuals will also be asked to 
remotely complete the Virtual Reality Sickness Questionnaire after each use of the VR 
program. Participants who are randomized to the VR group will be instructed to adhere 
to the usage recommendations specified by the VR program’s manufacturer. In addition, 
VR participants will be instructed not to use the VR device while ambulating, and that 
they should use the headset a maximum of 3 times per 24-hour period (morning, noon, 
and evening) for not more than 30 minutes consecutively. During the 8-week, home VR 

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use period, we will use telephone calls or text messages to conduct weekly study 
assessments of adverse events. Users of the VR program who experience adverse events 
are free to suspend or halt VR use at any time by removing the headset. This can remedy 
the VR side effects. In addition, the VR program offers a range of experiences to allow 
participants to identify lower risk experiences. For participants who experience adverse 
events, we will discontinue their study participation and refer them to a 
member of the medical team as needed for any medical follow-up. All participants will 
have the ability to withdraw from the study at any time. 
At this time, the risks of VR during pregnancy (i.e., risks to the pregnant woman, 
the embryo, or fetus) are not yet known. Therefore, to protect against possible side 
effects, women who are pregnant or nursing a child will not participate in exposure to 
VR. Female participants will be asked to immediately notify study staff if they become 
pregnant during the study. In that case, they will not be exposed to VR but may continue 
with other remaining study activities. 
Active suicidal ideation, as documented in the patient’s medical records, is one 
of the exclusion criteria. Among eligible participants, we will assess depression with the 
PROMIS® Emotional Distress – Depression (Short Form) at baseline, mid-treatment, and 
monthly post-treatment via remote data collection. This measure does not include a 
suicide item. To manage participants who score in the upper range of the depression 
measure or disclose suicidal ideation, we will utilize the following protocol. 
a. At the end of the survey in the questionnaire management system, 
participants will see this statement: If you are feeling distressed or you are 
having thoughts of hurting yourself, please call 911, call the 24-hour Georgia 
Crisis and Access Line at 1-800-715-4225, call the South Carolina 24-hour Crisis 
Response Dispatcher at 1-833-364-2274, go to Grady Memorial Hospital or your 
local hospital, or call your healthcare provider. 
b. The questionnaire management system will be designed to identify scores that 
indicate risk for serious depression (severe category) based on the scale’s 
psychometrics: mild (T scores of 55–60), moderate (T scores of 60–70), and 
severe (T scores > 70)64. These scores will be regularly monitored. Between data 
collection time-points, participants can also be assessed via the planned weekly 
text messages or telephone calls that will be used to promote engagement and 
retention. The PI will be immediately notified of any severe scores or disclosed 
suicidal ideation. 
c. Once notified, the PI will implement timely and appropriate follow-up to 
ensure the safety of the participants. We will inform participants that their 
responses indicate that they may be experiencing meaningful levels of 
depression and take the following steps to attempt to connect them with 
appropriate care during remote data collection. 
• If participants disclose suicidal ideation, we will contact them directly and 
“warm transfer” them to 911 or a crisis line (such as the 24-hour Georgia 
Crisis and Access Line, the 24-hour South Carolina Crisis Response 

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Dispatcher, or Emory Healthcare’s 24-hour crisis line). The Georgia Crisis 
and Access Line and the South Carolina Crisis Response Dispatcher 
provide a number of services, including screening and assessment of 
callers for intensity of service response, conducting “warm transfer” of 
individuals to 911 for emergencies, and crisis assistance (24/7 mobile 
response to assess the situation, de- escalate the crisis, consult, and refer 
with post-crisis follow-up to assure linkage with recommended 
68 
services). “Warm transfer” refers to the process of transferring a call 
while having the opportunity to share information with the crisis line 
staff prior to the call transfer. This also allows for all of us (i.e., research 
personnel, crisis line staff, and participant) to be on the call at the same 
time if needed. 
• If participants experience severe depression scores, we will contact them 
directly and refer them to Grady Memorial Hospital (Emergency 
Department or Behavioral Health Outpatient Center) or the emergency 
department at their local hospital for treatment. 
• These participants will be provided with a list of mental health resources. 
They will also be encouraged to follow up with their primary care 
practitioner about their symptoms or they can give us permission to 
contact the practitioner on their behalf. 
• A clinician (clinical psychologist) will be able to provide additional 
assistance if needed. 
We will conduct an internal study review and these participants will be given the option 
to discontinue the study or continue study procedures. The PI will document all of these 
activities. 
If adverse events occur, the date and time of onset and outcome, course, 
intensity, action taken, and causality to study treatment will be assessed by the PI. The 
PI will also review the outcome and adverse event data to determine whether a change 
to the anticipated risk-to-benefit assessment is required, and whether the study should 
continue as originally designed or should be revised. The IRB will be informed 
immediately of any adverse events and requests for modifications of the study protocol 
will be submitted quarterly. Confidentiality of the data and the results of monitoring will 
be protected. 
16. Potential Benefits to Participants 
Potential study risks are reasonable in comparison to the benefits and 
knowledge that will be gained from the study. Benefits of the study may include 
education regarding pain self-management, enhanced pain self-management skills, 
improved coping with pain, and decreased use of opioids for pain among adults with 
SCD. Participants may also receive an indirect benefit by sharing their information as a 
part of a larger study that will result in future interventions for enhancing the well-being 

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of individuals with SCD. Knowledge gained from the study can be used by healthcare 
professionals to provide better care to adults living with SCD and to better equip 
patients with the resources and skills necessary to effectively participate in theirown 
pain management. In addition, information obtained from the study will help to 
decrease stigmatization experienced by members of this population. 
17. Compensation to Participants 
Participants will receive compensation in the form of gift cards (physical or electronic) 
throughout the study. They will receive $50 after baseline, $50 after each 4-week study period 
($150 in total), and $50 after the qualitative sessions. 
18. Data Management andConfidentiality 
Data Management 
Electronic methods, including REDCap and Microsoft Office, will be used to 
organize and manage data collected from this study. A data collection log will be used to 
enable tracking of data collection activities. Data collection logs will specify what data 
are to be collected for each participant, using which instruments, with expected and 
actual dates of data collection. Detailed reports of completed instruments listed by 
participant identification number will be generated for program management purposes; 
for instance, to plan for conducting focus group sessions or individual interviews. 
Data Analysis 
Data will be collected and managed by using REDCap. All quantitative data will be 
verified and periodic quality assurance checks of data entry will be performed. Once finalized, 
data will be exported from REDCap into the Statistical Package for the Social Sciences (SPSS 
Version 26) for statistical analysis. We will code the surveys manually and evaluate their 
psychometric properties in the sample. Initial data analysis will include descriptive statistics 
(e.g., means, standard deviations, frequencies, and percentages) on sample characteristics and 
outcomes at each time point. To ensure balance in participants’ characteristics by intervention 
group at baseline, we will compare the sociodemographic and clinical characteristics (e.g., age, 
gender, disease severity, and comorbidities) of participants using t-tests or chi-square tests as 
appropriate. Any differences across treatment groups will be accounted for in subsequent 
analysis. We will also evaluate any attrition according to participants’ characteristics. We will 
assess distributional assumptions of outcomes and perform appropriate transformations to 
remedy any violations. We will minimize missing data by monitoring data regularly and 
implementing successful methods for obtaining follow-up data. When data cannot be collected, 
sensitivity analysis will be performed to evaluate the impact of missing data on results. We also 
plan to use the restricted maximum likelihood (REML) method for model estimation whenever 
possible to minimize the impact of missing data. All outcomes will be compared among 
participants in both arms. All statistical tests will be two-sided and intent-to-treat procedures 

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will be employed. Additionally, all analyses will include sex (male vs female) as a biological 
variable to assess differences in outcomes within each group. 
Number and percent will be used to summarize the primary feasibility measures while 
content analysis will be used to summarize the secondary feasibility measures. Optimal 
treatment will be determined by correlations among the engagement outcomes and measures 
of preliminary efficacy. We will use mixed-effects models to test whether the outcomes differ 
across the treatment group over time (from pre- to post intervention). Depending on the type 
of outcome (continuous or categorical), linear or generalized mixed effects models will be used, 
respectively. In this approach, each participant is treated as an experimental unit with repeated 
observations over time. The model will include fixed effects of time, intervention group, and 
time x intervention group interaction, and assume an unstructured variance–covariance matrix 
to describe the covariance structure. We will adjust for any baseline group differences in 
participant characteristics. A significant interaction effect will indicate significant differences in 
outcomes by treatment groups over time. We will select the most parsimonious model using 
Akaike information criterion (AIC) and Bayesian information criterion (BIC). Hypotheses tests 
based on specific contrasts in the mixed model and the interaction term between time and 
intervention group will be performed to test whether subjects in the intervention group 
demonstrated improved outcomes compared to the control group. The model-based estimates 
of the outcome measures for the two treatment groups at each time point will be used to 
estimate effect sizes for future studies. 
Interview data will be transcribed verbatim then checked for accuracy by the PI before 
being subjected to content analysis.69,70 A TAM-based codebook will be used to assist with 
analysis. Codes may include TAM constructs related to user intent, usage behavior, usefulness, 
and ease of use.45,46 We will review transcripts to assign codes based on concepts that emerge, 
select exemplars illustrating these concepts, and sort codes into categories. As analysis 
progresses, constant comparison will be used to refine existing codes and identify new codes to 
fit the data.69,70 As the qualitative sessions progress, information gleaned from earlier sessions 
may be used to modify later sessions so that findings are confirmed by multiple participants. 
We will review findings for accuracy of data interpretations, themes generated, and 
conclusions. 
Confidentiality 
To protect confidentiality and maintain the privacy of study participants, we will strictly 
adhere to HIPAA protocol and use a Certificate of Confidentiality. All data will be kept 
confidential and will only be used for research purposes. The PI will ensure that study records 
are stored securely. All paper study records will be stored in locked file cabinets in a locked 
office at Emory University’s Nell Hodgson Woodruff School of Nursing, to which only the PI and 
research staff will have access. A copy of the signed informed consent form and any identifying 
numbers will be placed in a secure file cabinet that is separate from other study records. A copy 
of the completed verbal informed consent form will be stored on password protected 
University computers that contain data encryption software and computer locks to prevent 
theft. Each participant will be given a unique study identification number that does not reveal 

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personal identifying information. Relevant medical information will be written on study forms, 
which will have the participant’s study number only. Additionally, during each interaction as a 
part of the study, we will inform prospective participants that no study data will be entered 
into their medical records or provided to anyone without their written permission. 
Although all study related documents will only be labeled with a unique participant 
number that does not contain any identifying information, there is a need to link the participant 
number to personal identifiers in order to contact study participants after baseline data 
collection. A linkage document will be stored on a password protected, encrypted network 
drive. Personally identifiable information will be accessible only to study personnel. There will 
be blinding of the statistician to group assignments. The code for random assignments will be 
kept in a hidden folder that is not accessible to any study staff with patient contact or data 
analysis responsibilities. The statistician will receive two groups of datasets marked as group A 
and B. These groups will be randomly labeled by the project coordinator before the datasets are 
sent to the statistician. Using this method, the PI, co-I, and statistician will remain blind to group 
assignments until after data are collected and analyzed. 
Electronic data will be collected and stored via secure databases such as REDCap and 
AppliedVR’s software system (for device usage data). All downloaded electronic data will be 
saved in password protected files. Additionally, all computers on which data will be stored and 
evaluated are password protected, will have data encryption software, and will have computer 
locks to prevent theft. All computers have a privacy screen so that information displayed on the 
monitor is not visible to others unless seated directly in front of the monitor. Data may be 
shared among the research team in person or via secured university email. Any shared data will 
not include identifying information and participants will not be identified in any report or 
publication about this study. All identifiable data will be destroyed after completion of the 
study and dissemination of findings. Digital files will be kept for 5 years and then will be 
destroyed. 
19. Provisions to Monitor the Data to Ensure the Safety of Participants 
The PI will be primarily responsible for study monitoring. All study personnel will 
complete CITI and HIPAA training prior to initiating any work with study participants. Quality 
oversight to measure fidelity to study procedures will be conducted by the PI and the research 
team. Measures for safeguarding the security of study data will include: ensuring that all study 
personnel will maintain required IRB certification; when in use, keeping paper study documents 
safe from public view; assigning a non-identifiable study number to each participant; ensuring 
that all devices used to collect, store, and review study data are password-protected; collecting 
and storing electronic data via secure databases; storing paper documents in secured, locked 
areas; restricting access to data to authorized personnel only; and de-identifying participants’ 
data for use in reports or publications. 
The PI, co-investigator, and project coordinator will meet weekly at the study outset 
then monthly to assess study goals, timelines, participant recruitment and retention, data 
quality, data coding and management, and identification and documentation of unanticipated 
problems, complaints, or breach of confidentiality. If participant enrollment falls below 50% 
within two months of initiation of enrollment, or adherence falls below 50%, both of which 

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might inhibit the ability to test study outcomes, the PI will meet with the study team to discuss 
alternative methods for improving recruitment and adherence. 
Data on adherence to the treatment protocol will be collected twice weekly by research 
staff and reviewed weekly by the PI. Participants’ compliance with treatment will be evaluated 
by the frequency of program use and actual minutes used. Monthly assessments will made of 
protocol compliance, participant recruitment, accrual and retention, participant withdrawals, 
data quality and timeliness, risk-to-benefit evaluation, unanticipated problems (including 
adverse events), protection of confidentiality of information, and any other factors that may 
affect the study. In the case of adverse events, the date and time of onset and outcome, course, 
intensity, action taken, and causality to study treatment will be assessed by the PI. The PI will 
also review the outcome and adverse event data to determine whether a change to the 
anticipated risk-to-benefit assessment is required, and whether the study should continue as 
originally designed or should be revised. The IRB will be informed immediately of any adverse 
events and requests for modifications of the study protocol will be submitted quarterly. 
Confidentiality of the data and the results of monitoring will be protected. 
A summary of the following assessments will be provided to the IRB annually at the time 
of study renewal or more frequently as required: list of research personnel who participated in 
the data and safety monitoring; the frequency of monitoring that took place during the renewal 
intervals and/or the dates on which data and safety monitoring was conducted; cumulative 
data related to unanticipated problems, including a determination of causality and a re- 
evaluation of the risk-to-benefit assessment; if applicable, pertinent scientific literature reports, 
therapeutic developments, or results of related studies that may influence the safety of study 
participants or the ethics of conducting the research study; outcome of reviews conducted to 
ensure participants’ privacy and the confidentiality of research data; final conclusions regarding 
changes to the anticipated risk-to-benefit assessment of study participation; and final 
recommendations related to continuing, changing, or discontinuing the study. 
20. Provisions to Protect the Privacy Interests of Participants 
We will strictly adhere to HIPAA regulations to safeguard participants’ privacy 
interests and their protected health information (PHI). We will ask permission to access 
and utilize any PHI, such as through the electronic medical record. All data will be kept 
confidential and will only be used for research purposes. The steps that will be taken to 
protect confidentiality and maintain the privacy of study participants will be outlined on 
the informed consent. These steps include: using a study number, rather than the 
participant’s name, in data records, presentations, or publications; using a Certificate of 
Confidentiality; utilizing data use agreements for any future researchers who may want 
access to de-identified study data; not placing their research data into their electronic 
medical record; and not sharing any information about them with unauthorized 
individuals or without their written permission. If desired, participants will be able to 
revoke their permission for use of their PHI at any time during the study by contacting 
the study team in writing. We will help participants feel at ease with this study during 
the informed consent process and throughout the study by providing detailed 
information regarding the study purpose, research activities, their rights as a study 

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participant, their ability to choose not to answer any questions at any time, and their 
ability to discontinue participation at any time. 
21. Economic Burden to Participants 
There are no anticipated costs to patients for participating in this study. Participants will 
not be charged for any of the research activities. 
22. Consent Process 
The consent process will be completed by the project coordinator or principal 
investigator and will take place in person, in a private area of the SCD clinic, SC 
Foundation, research center, or remotely. After screening, eligible patients will receive 
information about the study. At least 15 minutes will be devoted to the consent 
discussion during which the study will be described to patients, they will be asked to 
explain what they understand about the study, and they will have an opportunity to ask 
questions and take any necessary time that is desired prior to making a decision 
regarding participation. Once an affirmative decision has been made, individuals will be 
asked to complete the informed consent and HIPAA authorization form. If there is 
period of more than 60 minutes between the initial consent discussion and an 
affirmative decision to participate in the study, the project coordinator or principal 
investigator will review the consent discussion prior to obtaining consent. While study 
activities are being conducted remotely post-baseline, the project coordinator or 
principal investigator will remind the participants of their continued rights and assess 
their understanding of the study to ensure ongoing consent. This assessment of ongoing 
consent will be completed by the project coordinator or principal investigator during 
the check-ins that will be conducted via text messages or telephone calls and prior to 
conducting the post-intervention interviews. To minimize the possibility of coercion or 
undue influence, participants will be reminded that neither their study participation nor 
decision not to participate will influence their healthcare in any way. 
In the event of any study changes or the need for remote consent, study staff 
will contact participants via telephone or Zoom (audio only) and they will be asked to 
provide verbal informed consent after the consent discussion takes place. As an option, 
e-consent may be utilized for completion of the informed consent form and electronic 
signature of consent may be used by study team members obtaining verbal informed 
consent. If participants request a copy of the revised consent form, then they will be 
emailed a link to the online consent form in REDCap. The email will not contain any 
information related to the participant’s condition. 
Non-English-Speaking Participants: Not applicable 
The target population for this study consists of Black or African American adults with 
SCD. Members of this population are proficient with the English language. 
 
Participants who are not yet adults (infants, children, teenagers): Notapplicable 
 

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Cognitively Impaired Adults: Not applicable 
Adults Unable to Consent: Not applicable 
Waiver or Alteration of Consent Process (consent will not be obtained, required 
information will not be disclosed, or the research involves deception): Not applicable 
23. Setting 
The research team will identify and recruit potential participants at the Georgia 
Comprehensive Sickle Cell Center at Grady Memorial Hospital (Grady) in Atlanta, 
Georgia and the James R. Clark Sickle Cell Memorial Foundation (SC Memorial 
Foundation) in Columbia, South Carolina. After baseline, research procedures will be 
conducted remotely while participants are at home or may be conducted in a private 
area of the research center (Nell Hodgson Woodruff School of Nursing at Emory 
University) or the SC Memorial Foundation if in-person activities are necessary. 
24. Resources Available 
Of the 1100 adults annually served by the SCD center, over 50% are ages 18–40 
and experience chronic pain, and approximately 30 individuals in this age range are seen 
in the SCD clinic weekly.71,72 In addition, the SC Memorial Foundation has a client roster 
of approximately 400 adults. Therefore, it is feasible to recruit the required number of 
suitable participants (n = 50). 
Medical resources (such as Grady or local area hospitals) and psychological 
resources (such as the Georgia Crisis and Access Line, the South Carolina Crisis 
Response Dispatcher, or local area hospitals) will be available to participants to 
address any unanticipated consequences of this research. A clinician (clinical 
psychologist) will also be available to provide additional assistance if needed to 
manage participants who score in the upper range of the depression measure or 
disclose suicidal ideation during the study. 
During the two-year study period projected for completion of research activities, 
the percentage of time that will be allocated to conducting and completing the research 
is 100% for the project coordinator, 30% for the PI, and 5% for the co-PI. The PI will be 
primarily responsible for study monitoring. Prior to the start of the study and routinely 
throughout the study, the PI will meet with all study personnel to ensure that they are 
adequately informed regarding the study protocol, research procedures, and their roles 
and responsibilities, and that they complete CITI and HIPAA training prior to initiating 
any work with study participants. 

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