Cereset Research To Reduce Stress In Healthcare Workers In The Time Of COVID-19
Phase: NA
Conditions: Health Personnel, Stress, Anxiety, Insomnia, Hyperarousal, Corona Virus Infection, Covid19
Sponsor: Wake Forest University Health Sciences

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cereset Research to Reduce Stress in Healthcare Workers in the Time of COVID-19 
 
Brief Title: Cereset Research In Healthcare Workers During COVID-19 
 
08/02/2022 
 
NCT04682197 
 

 
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Title: 
Cereset Research to Reduce Stress in Healthcare Workers in the Time of COVID-19 
Principal Investigator: 
Charles H. Tegeler, MD1 
Department of Neurology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC  27157-1078 
E-mail: ctegeler@wakehealth.edu 
Phone: 336-716-7651 
Fax: 336-716-5813 
 
Funding: The Susanne Marcus Collins Foundation, Inc. 
Key Words: stress, anxiety, COVID-19, Coronavirus, neurotechnology, autonomic dysregulation, acoustic 
stimulation, neuromodulation, hyperarousal, brain electrical activity, wellbeing, allostasis, HIRREM, 
Cereset Research 

 
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Abstract: 
This study will enroll up to 166 healthcare workers, age 18 or older, who have symptoms of stress with a 
goal of 138 to complete the intervention. Participants will be randomly assigned to either an Early 
Intervention (EI) group which will receive 4 CR sessions of audible tones echoing current brainwave 
activity, following enrollment, or a Delayed Intervention (DI) group which will continue current care only 
and will serve as a control group.  Participants in both groups will continue their other current care 
throughout the study.   
The primary outcome will be change in stress as measured by the Perceived Stress Scale (PSS).  
Secondary outcomes to be collected include symptom inventories for insomnia (Insomnia Severity 
Index, ISI) and anxiety (Generalized Anxiety Disorder-7, GAD-7).  Exploratory measure include depression 
(Center for Epidemiological Studies- Depression Scale, CES-D), traumatic stress (PTSD Checklist for 
civilians, PCL-C), overall quality of life (QOLS), social support (ISEL-12), the Multiple Ability Self-Report 
Questionnaire (MASQ) for cognitive function, Fatigue Severity Scale (FSS) for fatigue, and mental health 
(Depression, Anxiety, and Stress Scale, DASS-21).  Details about COVID-19 status, interaction, workplace 
engagement, healthcare utilization, and exposure will be collected.  Pre- and post-intervention data 
collection of physiological parameters (Heart rate, HR, and measures of autonomic cardiovascular 
regulation assessed by heart rate variability) will also be assessed as exploratory outcomes.   
Symptom questionnaires will be collected at an enrollment visit (V1), and participants will be randomly 
assigned to the EI or DI groups.  For those in the EI group, the intervention will begin 0-7 days thereafter.  
Sessions will be administered over 10 business days.  Follow-up data collections will be obtained at 2 
weeks following enrollment (V2) [0-14 days after completion of the intervention for the early 
intervention group], and 4-7 weeks after the V2 (V3, primary outcome).  Following V3, those in the DI 
group will be offered the opportunity to cross over to receive 4 CR intervention sessions and will 
continue to be followed for data collections at 0-14 days (V4) after completing their sessions, and 4-7 
weeks (V5) after V4.  Mean contrasts will be used to compare the changes in measures of perceived 
stress (PSS) from V1 to V3, the primary outcome, in the early vs. delayed intervention groups. Similar 
analysis will occur for secondary outcomes.   
Background, Rationale, and Context: 
Background: 
Abnormal electroencephalographic (EEG) asymmetries have been reported in a variety of neurological, 
cardiovascular, and psychophysiological conditions including insomnia, attention deficit hyperactivity 
disorder (ADHD), anxiety, autism spectrum disorders, depression, dyslexia, post-traumatic stress 
disorder (PTSD), and traumatic brain injury (TBI) (Avram, Baltes, Miclea, & Miu, 2010; T. S. Hale et al., 
2010; Hale et al., 2009; T.S. Hale et al., 2010; Kemp et al., 2010; Lazarev, Pontes, Mitrofanov, & 
deAzevedo, 2010; Marzano, Ferrara, Sforza, & De, 2008; Metzger et al., 2004; Moscovitch et al., 2011; 
Rabe, Beauducel, Zollner, Maercker, & Karl, 2006; Riemann et al., 2010; Spironelli, Penolazzi, & Angrilli, 
2008; Stroganova et al., 2007; Thibodeau, Jorgensen, & Kim, 2006; Wolynczyk-Gmaj & Szelenberger, 
2011).  Many, if not all of these conditions are associated with autonomic imbalance and 

 
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psychophysiological dysfunction manifested as low heart rate variability or other abnormal measures 
(Beckham et al., 2003; H. Cohen et al., 2000; Katz-Leurer, Rotem, Keren, & Meyer, 2010; Spiegelhalder et 
al., 2011; Tobaldini et al., 2013). 
Autonomic regulation of the cardiovascular system can be evaluated by measuring heart rate variability 
(HRV) or baroreflex sensitivity (BRS).  HRV can indicate the physiological capacity to produce dynamically 
varied responses to the changing needs of an environment.  Prospective studies show that decreased 
HRV is a risk factor for incident cardiovascular disease (Tsuji et al., 1996) and all-cause mortality (Dekker 
et al., 1997). In addition, depressed HRV is often reported across behavioral disorders (Beauchaine & 
Thayer, 2015), including military personnel and veterans with diagnosed PTSD (E. A. Lee et al., 2013; 
Minassian et al., 2014; J. Park et al., 2017; J. E. Park et al., 2017; Shah et al., 2013), and as a pre-
deployment predictor of new post-deployment PTSD diagnoses or symptom severity (Minassian et al., 
2015; Pyne et al., 2016).  In adults, low HRV is also a risk factor for adverse cardiovascular outcomes 
(Kleiger, Miller, Bigger, & Moss, 1987; Tsuji et al., 1996), new onset of diabetes (Carnethon, Golden, 
Folsom, Haskell, & Liao, 2003), progression of chronic kidney disease (Chandra et al., 2012), and all-
cause mortality (Dekker et al., 1997).  Due to the pervasiveness of diminished HRV in behavioral health 
disorders, it has also been suggested as a trans-diagnostic biomarker for psychopathology (Beauchaine 
& Thayer, 2015).  As a measure that can be obtained easily and noninvasively, HRV warrants 
consideration as a target for observation and intervention on a public health basis (Marsac, 2013).  HRV 
may also inform and support the development and dissemination of advanced practices which are 
beneficial for physical and mental health, or adaptive neurovisceral integration (Thayer, Hansen, Saus-
Rose, & Johnsen, 2009).   
A wide variety of behavioral, physical exercise, and pharmacological therapies have been shown to 
increase HRV (Nolan, Jong, Barry-Bianchi, Tanaka, & Floras, 2008).  Especially for interventions that 
entail relatively non-specific features, the effects likely depend on the capacity to influence both central 
and peripheral nervous system pathways.  An important question is whether focused engagement of 
critical central structures, especially those known to have specific roles for autonomic management, 
may be a way to produce more efficient or impactful effects on HRV.   
The bihemispheric model for autonomic management of traumatic stress (Lee SW., 2014) begins with 
recognition that the right and left hemispheres are primarily responsible for cortical management of the 
sympathetic and parasympathetic divisions, respectively.  The BHAM suggests that temporal lobe 
electrical asymmetry may be an indication of traumatic stress exposure, associated with health effects 
including reduced HRV.  It also suggests that interventions to reduce asymmetrical activity may be a way 
to de-rigidify what have become stuck stress response patterns to facilitate a state of enhanced 
autonomic flexibility and dynamic range, including increased HRV.  Closed-loop therapies with real time 
monitoring for modulation of biological function offer a precision-guided, patient-centric strategy for 
brain-based therapies (Bellesi, Riedner, Garcia-Molina, Cirelli, & Tononi, 2014).  Healthcare workers 
experience constant stress, exacerbated during the COVID-19 pandemic, work long hours, and are more 
vulnerable to developing rigidified stress responses.  This study is important because it offers a nondrug, 
noninvasive alternative to medications to help healthcare workers mitigate, and manage stress and 
develop resilience.   

 
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HIRREM: 
High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®), developed by 
Brain State Technologies (BST), LLC, Scottsdale, AZ, is a commercially available, noninvasive, closed-loop, 
allostatic, acoustic stimulation neurotechnology  to facilitate client-unique relaxation and auto-
calibration of cortical neural oscillations by echoing auditory tones in near real time (Gerdes, Gerdes, 
Lee, & Tegeler, 2013).  HIRREM is intended to support more adaptive forms of symmetry at the 
temporal lobes and other cortical regions.  HIRREM is aligned with the BHAM as well as the broader 
physiological paradigm of allostasis (stability through change), which recognizes the brain as the organ 
of the central command (Sterling, 2012).  As a closed-loop neurotechnology (i.e., an intervention whose 
inputs are objectively measured real-time neurological data), HIRREM does not depend on conscious, 
cognitive activity, volitional self-regulation, or behavioral monitoring.  
Relevant Pilot Data: 
Since 2011, the HIRREM Research Program at WFSM has enrolled over 600 participants in eight IRB-
approved clinical studies to evaluate the effects and potential benefits of HIRREM.  Participants in these 
studies have received a total of over 6,000 HIRREM sessions.  Use of HIRREM has been associated with 
reduced sleep symptomatology and reduced high frequency amplitudes in adults with insomnia (C. H. 
Tegeler et al., 2012), reduced menopausal symptoms in women (C. H. Tegeler, Tegeler, Cook, Lee, & 
Pajewski, 2015), improved sleep in athletes with persisting post-concussion symptoms (C. H. Tegeler et 
al., 2016), and reduced temporal lobe high frequency asymmetry and symptoms in self-reported post-
traumatic stress (C. H. Tegeler et al., 2017), and reduced symptoms of military-related traumatic stress 
(Catherine L. Tegeler et al., 2017).  For the latter military cohort, maximal reduction in symptom scores 
was observed at one month following completion of the intervention.  Improved autonomic 
cardiovascular regulation has also been observed in those receiving HIRREM, including a cohort of 
adolescents with Postural Orthostatic Tachycardia Syndrome (Fortunato et al., 2016).  In addition, 
correlation has been reported between high frequency electrical brain pattern asymmetry scores at 
baseline, and measures of autonomic cardiovascular regulation (C. H. Tegeler, Shaltout, Tegeler, Gerdes, 
& Lee, 2015).  There was improved network connectivity on whole brain rest MRI was observed in 
participants with military-related traumatic stress (S. W. Lee et al., 2018). 
Notably, a placebo controlled efficacy trial of in-office HIRREM for moderate to severe insomnia 
demonstrated a clinically meaningful reduction of insomnia symptoms (≥ 6 point reduction on the ISI), 
and statistically significant additional benefit associated with use of HIRREM at two months post-
intervention, as compared to a sham placebo of random audible tones not linked to brainwaves (C. L. 
Tegeler et al., 2017).  HIRREM was well tolerated, and the benefit was durable through the final post-
intervention data collection (4 months).  The symptom-related primary outcomes from this large, 
controlled trial are highlighted in Figure 1 below.  
Continuous recording (10 minutes) of blood pressure and heart rate also allowed for analysis of 
autonomic cardiovascular regulation, including multiple measures of HRV and BRS.  This physiological 
data was obtained at all study visits.  Analysis also demonstrated significant improvement in multiple 

 
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objective measures of autonomic cardiovascular regulation including increased BRS (HFα, and Sequence 
ALL) and HRV (SDNN, and rMSSD), associated with this short term use of in-office HIRREM, compared to 
the placebo intervention of random audible tones not linked to brainwaves (Figure 2).  The benefit was 
seen at all follow up data collections, and was durable through the final follow up visit at 4 months post-
intervention (Shaltout, Tegeler, Lee, & Tegeler, 2017).  There was no significant improvement in 
autonomic function observed in the placebo group at any time point.  It is not clear whether these 
results reflect a cause, an effect, or both, relative to the observed improvement of insomnia symptoms.   
Figure 1: 
 
Figure 2: 
 
New Developments: 

 
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In spite of the many benefits demonstrated in the above-mentioned studies, and highlighted by the 
placebo-controlled trial for insomnia, the in-office HIRREM approach used for research since 2011 
remains very operator dependent.  This, and the time required for sessions (typically 10-20 sessions of 
90-120 minutes each), limit the scalability of the intervention.  To reduce the length of sessions, and 
reduce operator dependence, while increasing scalability, an updated version of hardware, and 
software, with fewer sessions has been developed by BST, to be used with more standardized protocols 
and fewer sessions.  The upgraded platform for medical research using this technology has been 
rebranded as Cereset Research™ (CR).  Cereset is short for “cerebral reset.”  Cereset is currently offered 
commercially as a technique for relaxation, well-being, and stress management.  As a low risk general 
wellness device, Cereset is exempt from FDA regulation (personal communication, Brain State 
Technologies/Cereset) 
CR is based on the same core technology and algorithms for noninvasively identifying, and rapidly 
echoing brainwaves back as audible tones in a closed-loop paradigm, embodied in HIRREM.  The CR 
system includes the use of 64-bit processing architecture for faster feedback, the use of 4 sensors, and 
the use of standard protocols (while retaining flexibility with length and sequencing of the standard 
protocols), all done with eyes closed.  Four sensors are placed on the scalp at a time.  However, only one 
pair of sensors are actively echoing feedback.  The software automatically switches from one pair to the 
other between protocols.  This reduces the number of sensor placement changes needed during a 
session by half, resulting in shorter session time and fewer interruptions.  Although benefit was seen 
with in-office HIRREM, and CR uses the same core technology, the benefits of this new approach using 
fewer sessions and more standardized protocols requires confirmation.  This version of the technology is 
now limited to 4 paired sensor placement locations: F3/F4 and P3/P4, FP1/FP2 and T3/T4, C3/C4 and 
O1/O2, and AFZ/POZ and CB1/CB2.   
As of May 2021, 103 participants have enrolled in an exploratory study using CR for stress, anxiety, or 
insomnia, and preliminary results show significant improvement in symptom inventories including 
perceived stress, as with legacy HIRREM.  This study will evaluate the effects of a greatly reduced dose 
of CR in healthcare workers with symptoms of stress during the time of COVID-19.  The primary goal is 
to explore for change in the Perceived Stress Scale (PSS).  The secondary focus is to evaluate the effect 
of CR on anxiety and insomnia and to explore its potential effect on other self-reported symptoms and 
autonomic cardiovascular regulation.    
Based on the electrical pattern being observed in real time and being informed by prior research and 
clinical experience, the CR Smart Protocol computer software also chooses what design is needed – 
balance, coherence, or harmony – to best support the location being observed to relax itself at that 
moment.  This includes use of one-sided or two-sided relaxation depending on what is needed in each 
30 second to 1-minute time interval, and reduces variability and operator dependence of application.  
Within these placement options, the Technologist may still adjust the sequencing of protocols and the 
number of minutes at each location after reviewing session data.  CR incorporates the use of fewer 
sessions, compared to prior studies with HIRREM.  The new protocols for CR are expected to provide a 
robust majority of the benefits that have been reported to date with HIRREM, but this requires 
confirmation in research studies.  The increased standardization of the process, with reduced variability 

 
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of application and operator dependence, along with fewer sessions, will strengthen the scalability of the 
refined intervention. 
Participants in our Cereset exploratory study had an average of 8.6 (SD 1.4) CR intervention sessions 
over 13.7 (SD5.2) calendar days.  They were on site for 7.9 (SD 1.8) seat days.  There was a range of 4 to 
7 protocols run during session and session lasted from 40 to 64 minutes.   
Table 1. Preliminary Data: Cereset Outcomes from Exploratory Open-label Study  
Insomnia Severity Index (ISI) 
V1 
V2 
V3 
V4 
Count 
103 
98 
89 
79 
Mean (SD) 
12.9 (5.5) 
8.8 (5.2) *** 
7.1 (5.7) *** 
7.0 (5.1) *** 
Center for Epidemiological Studies- Depression Scale (CES-D) 
V1 
V2 
V3 
V4 
Count 
103 
99 
89 
80 
Mean (SD) 
19.6 (11.1) 
12.9 (8.4) *** 
11.4 (8.6) *** 
11.5 (9.1) *** 
Generalized Anxiety Disorder-7 (GAD-7) 
V1 
V2 
V3 
V4 
Count 
103 
99 
89 
80 
Mean (SD) 
9.1 (5.3) 
5.2 (4.4) *** 
4.4 (4.0) *** 
4.1 (3.7) *** 
Perceived Stress Scale (PSS) 
V1 
V2 
V3 
V4 
Count 
103 
99 
89 
79 
Mean (SD) 
19.8 (6.3) 
16.8 (5.9) *** 
14.7 (6.6) *** 
15.1 (6.2)*** 
Quality of Life Scale (QOLS) 
V1 
V2 
V3 
V4 
Count 
103 
99 
89 
78 
Mean (SD) 
80.3 (12.9) 
84.0 (11.9) *** 
85.9 (13.1) *** 
85.6 (13.6) *** 
PTSD Checklist for Civilians (PCL-C) 
V1 
V2 
V3 
V4 
Count 
103 
99 
88 
77 
Mean (SD) 
39.3 (11.5) 
31.7 (8.7) *** 
28.5 (9.1) *** 
27.8 (8.7) *** 
* = P < 0.05  
** = P < 0.01  
*** = P < 0.001 
 
 
 
 
 

 
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Note:  The mean (SD) duration from last session to V2 was 3.9 (6.0) days, from last session to V3 was 
42.7 (8.6) days, last session to V4 was 83.4 (12.4) days for the table above.   
Cohorts within this exploratory study are published for pain and caregivers. (C. Tegeler et al., 2021a, 
2021b)  
This pilot study will evaluate the effects of using this more standardized, approach, and fewer sessions 
with CR, in participants with self-reported symptoms of stress. 
Importance:  
This randomized, waitlist-controlled study will evaluate the effects of the use of CR intervention in 
healthcare workers with symptoms of stress during the period of COVID-19.  Healthcare workers of all 
types have been impacted personally, professionally, and financially by the pandemic, resulting in higher 
levels of stress and anxiety.  Additional, brief, noninvasive, non-drug strategies are needed to help 
mitigate the effects of the acute trauma associated with the pandemic.  The primary outcome will be 
change in Perceived Stress Scale (PSS) a measurement of how different situations affect feelings and 
perceived stress, in the early intervention group compared to delayed intervention control.  Data will 
also be collected on a variety of additional relevant symptoms including insomnia, anxiety and 
autonomic cardiovascular regulation, for which benefits have been shown in prior studies using HIRREM.  
Data collected will assess the effects of a low dose CR approach (only 4 sessions) to help participants 
begin to mitigate stress.  A successful outcome of reduced stress would suggest benefit for this more 
scalable, generalizable approach to the use of the CR technology.  The effect of this minimalist approach 
on autonomic function and other self-reported symptoms will also be explored.  This information will be 
useful for planning larger randomized trials in more homogeneous cohorts and evaluating the 
appropriateness of direct clinical implementation of the intervention.  The proposed study might also 
help to identify characteristics of individuals who may experience differential effects/benefits from this 
low dose application of CR.   
Healthcare Worker Burden: 
Data from the Wake Forest Baptist Health’s 2020 Personal Health Survey shows that WFBH has a great 
need for cost-effective therapies to help address emotional health including sleep trouble, stress, and 
depression.  Despite a smaller sample size due to COVID-19, the projected cost in medical claims and 
lost productivity for key emotional health outcomes are seen in Table 2.  This small cross-sectional 
analysis of WFBH shows over $6 Million dollars of healthcare costs.  If these results are generalizable 
across the enterprise, costs will be even greater (Source: Aggregate Health Analysis, WFBH Employees, 
BestHealth For Us 2020, 6/25/2020).   
Table 2. Key Emotional Health Outcomes from 2020 Personal Health Survey 
Outcome Measure 
Typical 
US % 
WFBH 
% 
# Within 
Guidelines 
# At Risk 
Projected Costs in Claims 
and Productivity 
Depression Distribution 
5.4% 
11% 
1271 
162 
$3,342,682 

 
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Sleep Distribution 
10% 
41% 
852 
581 
$2,277,520 
Stress Distribution 
40% 
19% 
1154 
279 
$414,315 
 
COVID-19:  
COVID-19 quickly became a world pandemic.  Researchers are trying to quantify downstream health 
effects of the associated acute trauma and chronic stress.  Studies demonstrate that the circumstances 
surrounding COVID-19 have increased symptoms of stress, anxiety, depression, and insomnia in the 
general public (Qiu et al., 2020; Rajkumar, 2020; Wang et al., 2020; Y. Zhang & Ma, 2020).  Other 
literature notes that people across the world have more fear, anger, and feelings of loneliness (Shuja, 
Aqeel, Jaffar, & Ahmed, 2020). Some studies suggest that women are more vulnerable to developing 
psychological distress and higher levels of posttraumatic stress symptoms (PTSS) in general (N. Liu et al., 
2020; Qiu et al., 2020).   
Quarantine periods over 10 days are associated with increased risk for PTSS (Brooks et al., 2020).  Across 
the world, many cities have faced multi-week lockdowns for public safety.  In addition to being stuck at 
home, constant bombardment of news and social media have also shown to increase the odds of self-
reporting anxiety (Gao et al., 2020).  Many healthcare workers and the general public are facing new 
challenges each day.   
Within the healthcare field, studies have shown that healthcare workers have a higher prevalence of 
anxiety, depression, somatization, and insomnia to nonmedical health workers  (Liang, Chen, Zheng, & 
Liu, 2020; McAlonan et al., 2007; K. Zhang, Zhou, Liu, & Hashimoto, 2020; Y. Zhang & Ma, 2020).  
Without new interventions or solutions to mitigate increased arousal, healthcare workers are at a higher 
risk of developing long-lasting health impacts of stress related to COVID-19.  One study highlighted that 
more than half of healthcare professionals reported depressive symptoms, 44.7% reported anxiety, and 
36.1% sleep disturbance (S. Liu et al., 2020).  Frontline workers also show more severe degrees of 
mental health symptoms than other healthcare workers (Lai et al., 2020). 
Sleep and social support are hypothesized to help mitigate the effects of stress on the body and 
decrease PTSS symptoms, specifically levels of anxiety, stress, and self-efficacy (N. Liu et al., 2020; Xiao, 
Zhang, Kong, Li, & Yang, 2020)).  
This study will focus on a heterogeneous group of healthcare workers including physicians, nurses, 
support staff (PA, NP, respiratory therapists, diagnostic personnel, etc.), mental health professionals, 
administration, and medical center staff.   
Objectives: 
The primary objective of this study is to evaluate the effect of CR to improve the Perceived Stress Scale 
(PSS) in healthcare workers with symptoms of stress, compared to waitlist control, at 4-6 weeks post 
intervention. 

 
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The secondary objective is to evaluate the effect of CR on self-reported symptom inventories of 
insomnia and anxiety.  We will also evaluate exploratory measures for mood, post-traumatic stress, 
quality of life, social support, cognitive function, and autonomic cardiovascular regulation (heart rate 
variability, HRV).  
Methods and Measures: 
Design: 
This will be a single site, open label, randomized, wait-list controlled, pilot clinical trial. 
Setting: 
Study visits and sessions will be conducted in Suite 504, Department of Neurology, Piedmont Plaza II.   
Subjects Selection Criteria 
Participants/Subjects: 
Healthcare workers aged 18 and older with symptoms of stress, who also meet the inclusion criteria 
outlined below, and are interested in receiving CR, will be offered enrollment.  The participant must be 
able to provide informed consent. 
Interested individuals, for whom no exclusions are identified, based on initial phone or email 
communications, will receive an email with details of the study, a link to a short video outlining the 
study, and a link to complete an online eligibility screening form.  Once the screening form is completed, 
it is reviewed by the study team.  If potential participants have no clear exclusions, the Study 
Coordinator will contact them to answer any questions.   
Those who respond positively to the question about risk for suicide within the last 3 months will be 
ineligible for enrollment and provided with a behavioral health resources list.  For individuals who are 
eligible, they will be sent a welcome email, which includes information about the study, a schedule of 
study visits, a “Process and Study Details” document and a copy of the current informed consent 
document for their review.  This study will not actively seek to enroll pregnant women.  However, 
because no adverse effects have been observed in the small number of pregnant women that have 
enrolled in prior studies, if they are otherwise deemed eligible based on the presence of an appropriate 
condition or symptom; they will not be excluded due to the pregnancy.    
Inclusion Criteria: 
• 
Employed healthcare workers aged 18 years and older. 
• 
Ability to comply with basic instructions and be able to sit still, comfortably during sessions.   
• 
Experiencing symptoms of stress meeting threshold score on the Perceived Stress Scale (PSS ≥ 
14).    
Exclusion Criteria: 

 
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• 
Unable, unwilling, or incompetent to provide informed consent/assent. 
• 
Physically unable to come to the study visits, or to sit still, comfortably in a chair for up to 1 
hour.  
• 
Severe hearing impairment (because the subject will be using ear buds during CR). 
• 
Weight is over the chair limit (400 pounds). 
• 
Currently enrolled in another active intervention research study. 
• 
Prior use of: HIRREM, HIRREM-SOP, Brainwave Optimization (BWO), Cereset, Cereset Home, or a 
wearable configuration of the same (B2, or B2v2). 
• 
Prior use of the following modalities within one month before enrollment: electroconvulsive 
therapy (ECT), prior use of transcranial magnetic stimulation (TMS), transcranial direct current 
stimulation (TDCS), alpha stimulation, eye movement desensitization and reprocessing (EMDR), 
brain spotting, neurofeedback, biofeedback, or deep brain stimulation (DBS). 
• 
Known seizure disorder. 
• 
Thoughts of active suicide within the last 3 months.  
• 
Current, significant symptoms of long-COVID.   
• 
Current medical student. 
Participants will be asked to report use of alcohol, recreational drugs, CBD products, chiropractic, 
cranial-sacral therapy, and bio-energy work during the intervention, and until V3 and then for the 
crossover group at V4 and V5. 
Sample Size: 
Up to 166 participants might be enrolled to get the target sample of 138 to complete intervention.  With 
this target sample size, the study will have 80% power with alpha of 0.05 to detect a clinically 
meaningful change in the perceived stress scale of 3 points, assuming PSS standard deviation similar to 
our Cereset Research exploratory study preliminary data (SD 5.62 for difference in PSS from V1 to V3). 
The clinically meaningful change of 3 points on the PSS was selected based on literature regarding 
clinically meaningful change in this scale, clinical experience of the investigators, and because this 
magnitude of change, if detected, would be clinically significant enough to warrant clinical 
implementation as the immediate next step. The selected target difference in the primary outcome is 
slightly higher than a minimally important difference of 2.19 to 2.66 points(Drachev et al., 2020), but it is 
greater than an established clinically relevant difference of 4 points demonstrated in a clinical 
sample(Plantinga, Lim, Bowling, & Drenkard, 2017). In addition to evaluating the primary question about 
whether the intervention results in a 3 point improvement in PSS scores at 4-7 weeks post intervention 
compared to waitlist controls, the study will also explore for potential targets for future research, 
including those taking selected medications, and those with comorbid conditions or symptoms of 
interest.  
 
Intervention and Interactions: 
Participants will be randomly assigned to either an Early Intervention (EI) group which will receive 4 CR 
sessions of audible tones echoing current brainwave activity following enrollment, or a Delayed 

 
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Intervention (DI) group which will continue current care only and will serve as a control group through 
the V3 follow-up visit.  Participants in both groups will continue their other current care throughout the 
study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Schedule of Activities 
 

 
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Cereset Research – COVID-19 Study Flow Chart:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Crossover DI Group 
 
 
 
 
V1 
Baseline/Enrollment 
(up to 60 minutes) 
 
-Informed consent 
 
-Baseline outcome measures 
 
-Randomized to EI or DI 
group 
 
EI (Early Intervention) 
Within 0-7 days of V1 
 
-Short baseline recording 
 
-4 sessions over 10 calendar 
days (60 minutes each) 
EI V2 [2 weeks] 
Within 0-14 days of final 
session (up to 45 minutes)  
 
-Repeat outcome measures 
 
V3 [4-6 weeks following 
intervention period] 
Within 4-7 weeks of V2 
(up to 45 minutes) 
 
-Repeat outcome measures 
 
-Study completed for EI 
group 
 
-DI group offered 
opportunity to cross over 
and receive sessions 
 
 
DI (Delayed Intervention)  
-Continue current care 
 
Crossover: 
 
-Short baseline recording 
 
-4 sessions over 10 calendar 
days (60 minutes each) 
 
 
 
V4 
Within 0-14 days of final 
intervention session (up to 
45 minutes) 
 
-Repeat outcome measures 
 
V5 
Within 4-7 weeks of V4 
(up to 45 minutes) 
 
-Repeat outcome measures 
 
-Study completed for DI 
group 
 
 
DI V2 [2 weeks] 
10-21 days after V1 
(up to 45 minutes) 
 
-Repeat outcome measures 
 

 
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Enrollment Visit: 
Informed consent is obtained, medical history and medication list are reviewed from the screening form 
(Appendix C), and collection of baseline measures is completed.  This will occur prior to the start of CR 
and will require about 45-60 minutes of time.  To promote good mental health and well-being, all 
participants will receive a listing of behavioral health resources at the V1 study visit.   
Number of CR Sessions and Length of Study: 
All baseline measures will have been collected during the enrollment visit.  Participants in the IE group 
will begin CR sessions 0-7 days following V1 data collection, and will receive 4 CR sessions, along with 
continued care.  CR sessions will occur while relaxing in a zero gravity chair, and are approximately 1 
hour in length.  The first two sessions must be received over 5 calendar days and all four should be 
completed within 10 business days.   
Participants in the IE group who begin sessions immediately after V1, receive sessions, have V2 
immediately, V3 four weeks after, may be in the study about 5 weeks.  At the other end of the spectrum, 
a participant who delays the start of sessions until 7 days after V1, and receives sessions, then does not 
get V2, or V3 until the end of the allowable visit windows, might be in the study for about 8-9 weeks.  
The DI group may be in the study for 10 to 18 weeks.   
Post-Intervention Data Collection Visits: 
Within 7 days after completion of the intervention, participants in the IE group will return for a post-
intervention data collection visit (V2).  Measures will be repeated.  This visit will take about 30-45 
minutes.  Those in the DI group will return for V2 10-21 days after V1, with target of 14 days.   
Between 4-7 weeks after completion of the V2, participants will return for the primary outcome data 
collection visit (V3).  This visit will require about 30-45 minutes, and will be considered the time point for 
assessing primary outcomes.  At the V3 visit, those in the EI group will be done with the study.  Those in 
the DI group will be offered the opportunity to crossover and receive sessions within the next month.  
After receiving sessions, there will be V4 and V5 data collections.   
Brainwave Assessment: 
The short baseline brainwave recording occurs as part of the first session.  The assessment creates a 
map of frequencies and amplitudes.  Our pilot data also suggest that this information is also useful for 
correlating with autonomic function (HRV), and that changes can be observed in frequencies and 
amplitudes from pre- to post-intervention.  For the assessment, with the participant in a sitting position, 
sensors are sequentially placed over up to two areas of the scalp to record two-minute epochs of data 
while the brain is at rest with eyes closed.  For the assessment, measurements are taken at homologous 
regions of the bilateral hemispheres according to the 10-20 International System at FP1/FP2 and T3/T4, 
and F3/F4 and P3/P4.  The data are processed to identify patterns and imbalances of frequencies and 
amplitudes.  The baseline brainwave assessment takes about 5 minutes to complete.   

 
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CR Sessions: 
Each session requires about 1 hour, and will include 2 paired protocols, working with different locations 
on the scalp.  Each protocol will typically last between 8-12 minutes.  For the sessions, with the subject 
comfortably at rest, sitting or reclining in a zero gravity chair, the sensors are placed over the specific 
target areas on the scalp corresponding with brain regions/lobes to be observed.  Frequencies and 
amplitudes are monitored in real time, and the dominant frequency within a chosen target frequency 
band, e.g. delta (0.5-3 Hz) is identified.  The dominant frequency is assigned an auditory tone, which is 
played back to the subject via earbuds with as little as a 4-8 millisecond second delay.  Thus, the brain 
pattern is echoed back to the participant from moment to moment, providing the brain with rapid 
updating about its frequencies, amplitudes, and patterns.  All protocols will occur with eyes closed, and 
participants will be instructed to relax.  Participants can fall asleep if they wish, without loss of effect 
since no conscious, cognitive activity is required with this closed-loop approach.     
Although similar in appearance to other methods such as neurofeedback, CR is distinctly different.  CR 
uses an algorithm-based approach to allow the brain to observe, and resonate with itself.  This non-
judgmental, closed-loop paradigm supports the brain to auto-calibrate, self-adjust, or relax, typically 
resulting in shifts toward improved balance and reduced hyperarousal.  There is no learner in the loop, 
no operant conditioning, no need to try to train one’s brain to do anything.  There is also no attempt to 
force the brain towards a standardized or ideal pattern of frequencies and amplitudes.  
As with HIRREM, the exact mechanism of the effect with CR remains to be fully understood, but may 
involve resonance between the echoed tones and oscillating brain networks, which can be thought of as 
being much like a musical instrument tuning itself.  A key aspect of observed beneficial effects may also 
be related to the observed improvement in downstream autonomic function, as evidenced by increased 
(improved) HRV and BRS, apparently associated with increased dynamic range and flexibility of 
autonomic responses managed by the brain. 
Outcome Measures: 
A series of measures will be collected at data collection visits (Appendix A; schedule of activities).  
Primary Outcome Measure: 
The Perceived Stress Scale (PSS) is a ten-item psychological instrument for measuring the perception of 
stress. It is a measure of the degree to which situations in one’s life are appraised as stressful. Items 
were designed to tap how unpredictable, uncontrollable, and overloaded respondents find their lives. 
The scale, with answers rated from 0-4, also includes a number of direct queries about current levels of 
experienced stress (S. Cohen, Kamarck, & Mermelstein, 1983). 
Secondary Outcome Measures: 
Insomnia:  

 
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The severity of insomnia symptoms is measured using two self-report symptom inventories with each 
data collection visit.  This includes the Insomnia Severity Index (ISI).  The ISI is a 7-question measure, 
with responses from 0-4 for each question, yielding scores ranging from 0-28(Bastien, Vallieres, & 
Morin, 2001; Morin, Belleville, Belanger, & Ivers, 2011).  
Anxiety: 
The Generalized Anxiety Disorder-7 (GAD-7) is a seven-item screening tool for anxiety that is widely used 
in primary care.  GAD-7 is a brief, reliable and valid measure of assessing generalized anxiety disorder 
(Spitzer, Kroenke, Williams, & Lowe, 2006). 
Exploratory Measures:  
Depression:  
The Center for Epidemiologic Studies Depression Scale (CES-D) is a depression scale, which will help to 
assess this co-morbidity.  CES-D is a 20-item survey assessing affective depressive symptomatology to 
screen for risk of depression(Radloff, 1977).  Scores range from 0-60, with a score of 16 commonly used 
as a clinically relevant cut-off (SmarrK.L., 2003).  If the CES-D score is > 35 on the V1 baseline survey the 
study coordinator will obtain more information about the depression (onset, duration, evaluation, 
hospitalization, treatment, other therapy), and again ask the initial screening questions for risk of 
suicide.   
Traumatic Stress:  
The PTSD Checklist for civilians (PCL-C), measures the American Psychiatric Association’s Diagnostic and 
statistical manual of mental disorders (DSM-IV) Criteria B, C, & D of PTSD symptoms based on traumatic 
life experience either in civilian life, or related to military service, respectively.  Seventeen items are 
rated on a Likert scale with a composite score range of 17 to 85.  A score of 44 or higher correlates with 
probability of civilian-related PTSD (Blanchard, Jones-Alexander, Buckley, & Forneris, 1996) . 
Fatigue: 
Fatigue Severity Scale (FSS) is a nine-item instrument to assess how fatigue interferes with daily 
activities.  Items are scored on a 7-point scale ranging from 1=strongly disagree to 7=strongly agree.  
Total scores range from 9 to 63 and the higher the rating demonstrates greater fatigue severity (Krupp, 
LaRocca, Muir-Nash, & Steinberg, 1989).  
Quality of Life: 
The Quality of Life Scale (QOLS) is a 16-item scale that was modified from a 15-item scale used in chronic 
disease patients.  Topics include different components of daily life such as relationships, community 
engagement, personal fulfillment, and recreation.  Each item is scaled from 1 to 7 and a sum score is 
calculated to represent higher levels of satisfaction in life (range is 16-112) (Carol S. Burckhardt & 

 
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Anderson, 2003; C. S. Burckhardt, Woods, Schultz, & Ziebarth, 1989; Offenbächer, Sauer, Kohls, Waltz, & 
Schoeps, 2012).   
The self-rating health question from the EQ-5D on a scale of 0-100 (0 = worst imaginable health state, 
100 = best imaginable health state) will also be administered (Balestroni & Bertolotti, 2012; Rabin & de, 
2001).   
Social Support: 
The Interpersonal Support Evaluation List – Shortened Version (ISEL-12) is a 12-item scale that was 
modified from a 40-item scale used to assess perceptions of social support.  Three dimensions are 
evaluated: appraisal support, belonging support, and tangible support.  Each item is scaled from 1 to 4 
for “Definitely True” to “Definitely False.” (S. Cohen et al., 1983; S. Cohen & Wills, 1985).  Scores are 
summed and higher scores correlate with more perceived social support.   
Cognitive Function: 
The Multiple Ability Self-Report Questionnaire (Seidenberg, Haltiner, Taylor, Hermann, & Wyler, 1994) is 
a self-report questionnaire commonly used to assess perceived cognitive dysfunction. The MASQ has 38 
items and assesses five cognitive domains, including language, visual/perceptual ability, verbal memory, 
visual memory, and attention (Williams & Arnold, 2011).    
Mental Health Status: 
The Depression, Anxiety, and Stress Scale (DASS-21) is a self-report scale with 21 items (Le et al., 2019; 
D. Lee, 2019).  These questions are divided into three subscales to depression, anxiety, and stress, 
respectively.  The depression subscale scoring ranges from normal (0-9), mild depression (10-12), 
moderate depression (13-20), severe depression (21-27, and extremely severe depression (28-42).  The 
anxiety subscale scoring ranges from normal (0-6), mild anxiety (7-9), moderate anxiety (10-14), severe 
anxiety (15-19), and extremely severe anxiety (20-42).  The stress subscale ranges from normal (0-10), 
mild stress (11-18), moderate stress (19-26), sever stress (27-34), and extremely severe stress (35-42).  
This scale is routinely used in COVID-19 (Wang et al., 2020) and SARS literature (McAlonan et al., 2007).   
Work Engagement:  
The absenteeism and presenteeism questions of the World Health Organization’s Heath and Work 
Performance Questionnaire (HPQ) will be administered to gauge work engagement.  This abbreviated 
subset of questions includes 11 questions for worked time (Kessler et al., 2004; Kessler et al., 2003) 
Healthcare Utilization: 
Hospitalizations, emergency department, urgent care and clinic visit counts will be collected for the prior 
3 months at enrollment, and then throughout follow-up.   
COVID-19: 

 
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Questions about COVID-19 experience, exposure, and demographics will be collected.  These details will 
allow us to characterize the population and decide if there is any correlation between exposure status 
(i.e. working in a particular high risk area) and symptom scores.   
Heart Rate (HR), and Heart Rate Variability (HRV): 
Continuous heart rate will be recorded while the participant is breathing normally in seated position for 
10 minutes using Faros 180 heart rate monitor (Bittium Corporation, Oulu, Finland).  Beat to beat 
intervals (RRI) files will be generated at 1000 Hz via the data acquisition software.  The files will be 
analyzed with Nevrokard HRV software (by Nevrokard Kiauta, d.o.o., Izola, Slovenia).  The recordings will 
be visually inspected to ensure data quality (dropped beats or gross motion artifacts are excluded) and 
the first 5 minutes of usable tracings will be analyzed.  Measures of heart rate variability (HRV) in the 
frequency domain will be derived and these measures will be integrated over specified frequency ranges 
(LF: 0.04-0.15 Hz; HF: 0.15-0.4 Hz).  Power of RRI spectra in LF, HF range (LFRRI and HFRRI) and total power 
(TP) will be calculated in normalized units and the ratio of LF/HF will be used as a measure of sympatho-
vagal balance. ("Heart rate variability: standards of measurement, physiological interpretation and 
clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing 
and Electrophysiology," 1996). Data are saved to Excel spreadsheets for further statistical analysis by 
study team members. 
Exploration for Unexpected Barriers, Challenges, or Detrimental Factors: 
A REDCap element will be added to data collection at V3 and V5, the final official data collection visit, 
seeking input regarding any challenges or barriers faced during the study related to factors such as 
availability of session dates or times, restrictive guidelines for when sessions need to occur, tasks 
performed during data collections, comfort of the session chair/equipment, difficulty sitting still, office 
location and accessibility trouble, competing other therapeutic modalities, length of the research study, 
or any other issues.   
Analytical Plan: 
Data will be analyzed using the most recent versions of SAS (SAS Institute, Inc., Cary, NC) or the R 
Statistical Computing Environment.  Histograms and descriptive statistics will be examined to evaluate 
the distribution of study outcomes.  Mean contrasts will be used to compare the changes in symptom 
scores for the primary outcome of Perceived Stress Scale from V1 to V3 in the early intervention vs. 
delayed intervention groups, as well as secondary and exploratory outcomes/symptom scores.  Linear 
mixed models, which can accommodate within-subject correlations due to repeated assessments over 
time, may also be used to generate point estimates for effect size along with 95% confidence intervals to 
support a future larger study if the results in this study do not support immediate clinical application, 
and potentially for other studies examining other outcomes or potentially more select samples.  The 
association of outcome measures with baseline participant characteristics will also be explored. 
Human Subjects Protection: 

 
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Subject Recruitment Methods: 
Subjects will be recruited by physician referral, word of mouth, and through advertisement (elevator 
ads, posters, flyers, table outside cafeteria, video overview of study, etc.).   
Informed Consent: 
The research staff will obtain written informed consent or assent from each competent subject. 
Subject Communication Methods: 
Participants will be contacted by phone, email, and texting during the study.  The study team is going to 
explore texting for appointment reminders and rescheduling.   
Videoconference Data Collection Visit Alternative: 
During this time of COVID-19, institutionally approved videoconferencing platforms might be used to 
interact with study subjects.  In person visits are preferred, but in case of office closures or safety 
reasons the study team might collect data collections through REDCap and videoconferencing.   
Confidentiality and Privacy: 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 
subjects, and maintaining all study information in a secure manner.  Per institutional policy, all research 
study participants will be assigned a hospital MRN number, if none already exists.  To help ensure 
subject privacy and confidentiality, only a unique study identifier number, and first name will appear on 
the data collection form.  Any other collected patient identifying information corresponding to the 
unique study identifier will be maintained on a separate master log.  The master log will be kept secure, 
on a separate, limited access user group on a shared network drive, with access limited to designated 
study personnel.  Following data collection, subject identifying information will be destroyed at the 
earliest opportunity, consistent with data validation and study design, producing an anonymous 
analytical data set.  Data access will be limited to study staff.  Data and records will be kept locked and 
secured, with any computer data password protected.  No reference to any individual participant will 
appear in reports, presentations, or publications that may arise from the study. 
Brain State Technologies, LLC (BST) may assist with brain pattern review and analysis.  To accomplish 
this, BST is provided with the first 8 characters from the randomly generated, 36-character identifier 
that the HIRREM software generates for each participant’s brain frequency and amplitude data, along 
with the participant’s age and gender, which are believed important for understanding brain patterns.  
No other participant-specific information is provided.   
Safety: 
Based on experience reported by Brain State Technologies/Cereset, garnered from provision of case 
management support, feedback from their clients (now reported to be about 130,000), and feedback 

 
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from the HIRREM provider community, as well as results from IRB-approved studies at WFSM (now over 
600 participants to receive HIRREM), we are not aware of any serious adverse events resulting from 
HIRREM sessions.   
Non-serious, temporary, and somewhat paradoxical effects have been reported by study participants.  
This includes things such as the participant reporting being more aware of, or more affected by their 
feelings, or by those around them, changes in sleep, including dreams, emotions, energy levels, or a 
feeling of fullness in the head or mild headache.  In the course of provision of HIRREM as part of nine 
IRB-approved studies at WFSM, such non-serious, temporary effects have been estimated to occur in 
ten percent or less of participants.  Based on recent analysis of a placebo controlled trial of HIRREM for 
moderate to severe insomnia (n = 107), such non-serious, temporary adverse effects, that were judged 
to go beyond the intensity, expression, or nature of pre-existing health conditions, were reported during 
study participation by 10.7% in the HIRREM group, and 13.7% in the placebo group.  All episodes were 
brief, typically resolving in hours to 1-2 days, but at the most lasted less than one week.  Skin irritation at 
the site from the paste used to affix the sensors to the scalp was reported by a single participant (<1%) 
(Personal communication).  Since CR uses the same core technology and approach as HIRREM, the risk 
profile is expected to be similar.  A participant in the Explooratory research study, who completed the 
Cereset Research intervention 3 weeks prior, committed suicide.  There have now been over 14,000 
people who have used this generation of the technology in clinical practice, and over 80 in similar 
research studies, with no other reports of serious adverse events.  It is not believed that the Cereset 
Research intervention played a causative role in this tragic event.   
All CR sessions are administered by Technologists who have been trained in the procedure, including 
guidelines for addressing any adverse effects that may occur.  In the event that any adverse effect is 
prolonged or intense, participants will be advised to see their primary care physician, or if needed, to 
see a mental health professional for additional evaluation or treatment.  It acute, and severe, 
participants will be referred to the Emergency Department.   
If the study team learns that a participant, or someone else is in danger of harm, the study team will 
report that information to the proper authorities.    
If someone has a 10 point or greater increase in depression (as measured by the CES-D) at a follow up 
visit, they will be given a community resources handout for mental health.  The increase is one standard 
deviation from the typical drop from baseline in the Exploratory Study.   
The manufacturer of Cereset Research recently provided the following update regarding safety and 
regulatory status: 
“This technological approach has been used across several branded versions in what are now about 
130,000 individuals, with no serious adverse events reported.  The device now branded as Cereset, 
which will be used in research studies as Cereset Research, uses the same core technology and approach 
as HIRREM, echoing brainwaves in real time as audible tones.  Cereset is commercially available as a 
wellness technology to help manage stress, restore hope, and achieve restful sleep.  Cereset software 
was tested hundreds of times in our office before going to production beginning in October of 2017.  

 
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Since then, thousands of sessions using Cereset software have been provided clinically in 25 other 
offices across the country without any issues.  Results thus far have exceeded our expectations. 
We previously shared that the HIRREM equipment used at WFSM since 2011, was registered with the 
FDA as a Class 2 device under regulation number 21 CFR 882.5050 (biofeedback device), and was thus 
exempt from FDA 510(k) pre-market notification procedures.  Based on the same core technology, with 
a well-documented, extremely favorable risk profile for this approach, the same applies for Cereset.  
Importantly, Cereset now falls under more recent FDA guidance provided in a document issued on July 
29, 2016, regarding General Wellness: Policy for Low Risk Devices.  As a low-risk, general wellness 
device, Cereset is exempt from FDA regulation.  Versions of Cereset Research are currently being used as 
part of IRB-approved research studies at the Uniformed Services University for Health Sciences, and 
Womack Army Medical Center, as well as at WFSM (as HIRREM-SOP).” (Lee Gerdes, CEO, Brainstate 
Technologies/Cereset, February 10, 2019, personal communication). 
Participant Compensation: 
Participants in this research project will not receive any monetary compensation.    
Data and Safety Monitoring: 
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study staff. 
Any collected patient identifying information corresponding to the unique study identifier will be 
maintained on a separate master log.  The master log will be kept secure, with access limited to 
designated study personnel.  Following data collection subject identifying information will be destroyed 
at the earliest opportunity, consistent with data validation and study design, producing an anonymous 
analytical data set.  Data access will be limited to study staff.  Data and records will be kept locked and 
secured, with any computer data password protected.   
Reporting of Unanticipated Problems, Adverse Events, or Deviations: 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the principal investigator or designated member of the research team to 
the IRB and sponsor or appropriate government agency if appropriate. 
 
 

 
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Appendices 
A: 
Perceived Stress Scale (PSS) 
Insomnia Severity Index (ISI) 
Generalized Anxiety Disorder 7-Item (GAD-7) 
Center for Epidemiological Studies Depression Scale (CES-D) 
PTSD Checklist for Civilians (PCL-C) 
Fatigue Severity Scale (FSS) 
Quality of Life Scale (QOLS)  
Interpersonal Support Evaluation List (ISEL-12) 
Multiple Ability Self-Report Questionnaire (MASQ) 
Depression, Anxiety, and Stress Scale (DASS-21) 
EQ-5D Self-Report Health State Question 
World Health Organization’s Heath and Work Performance Questionnaire (HPQ) 
*Workplace healthcare utilization, missed/medical appointments, etc.  
 
B: 
COVID-19 Healthcare Worker Study - Screening Video 
 
C: 
Handout for Study Participants – “Process and Study Details” 
 
D: 
Eligibility Screening Form  
 
E:  
Study Coordinator Email Script 
Study Coordinator Data Collection Forms 
Behavioral Health Resource List 
 
 
 

 
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