Use of the Frequen-ZZZ Sleep Pad to Increase Restorative Sleep: A Proof-of-Concept Study
Phase: NA
Conditions: Insomnia, Sleep, Sleep Disturbance
Sponsor: Kunasan Inc.

 
 
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HRP-592 - Protocol for Human Subject  
Research with Use of Test Article(s) 
 
Protocol Title: 
Provide the full title of the study as listed in item 1 on the “Basic Information” page in CATS IRB (http://irb.psu.edu).  
Use of the Frequen-ZZZ Sleep Pad to Increase Restorative Sleep: A Proof-of-Concept Study  
 
Principal Investigator: 
Name: Anne-Marie Chang 
Department: Biobehavioral Health 
Telephone: 814-863-5226 
E-mail Address: amchang@psu.edu 
 
Version Date: 
Provide version date for this document. This date must be updated each time this document is submitted to the IRB 
office with revisions.  DO NOT revise the version date in the footer of this document.  
12/08/2023 
 
Clinicaltrials.gov Registration #: 
Provide the registration number for this study, if applicable. See “HRP-103- Investigator Manual,” under 
“ClinicalTrials.gov” for more information.  
NCT05908344 
 
Human Research Protection Program 
Office for Research Protections 
101 Technology Center 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
https://www.research.psu.edu/irb 
 
 
 
 

 
 
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Table of Contents 
1.0 
Objectives 
2.0 
Background 
3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
Study Design and Procedures 
7.0 
Number of Subjects and Statistical Plan 
8.0 
Risks 
9.0 
Adverse Event Reporting 
10.0 
Study Monitoring, Auditing and Inspecting 
 
 
 

 
 
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1.0 
Objectives 
 
1.1 
Study Objectives 
 
We propose to examine the potential effects of the Frequen-ZZZ/Sleepergize sleep pad – a noninvasive, 
unobtrusive appliance that generates a magnetic gradient, and that is used on the bed – on multiple 
sleep outcomes in an 8-week randomized crossover study, and to calculate the effect sizes of the 
intervention to inform power and sample size for future studies. 
 
1.2 
Primary Study Endpoints 
 
Primary outcomes include changes in: 
-slow-wave sleep (e.g., stage N3 quantity, proportion, & power-spectral features) 
-sleep duration 
-sleep onset latency 
-sleep quality (e.g., frequency and duration of awakenings; sleep stage entropy measures) 
-insomnia symptoms (e.g. self-reports on the Insomnia Severity Index [ISI])  
 
1.3 
Secondary Study Endpoints 
 
 
Secondary outcomes include changes in: 
-other sleep stages (e.g. N1, N2, REM; quantity, proportion, & power-spectral features) 
-spindle characteristics (e.g., count, stage distribution, power-spectral features) 
-other subjective outcomes 
-inflammatory biomarkers  
 
Exploratory outcomes are changes in pain intensity, pain-related functional interference, and dream 
content valence. 
 
Additional data to be collected: 
These are not considered “Endpoints” because we are not planning an analysis that compares groups 
based on the following criteria. This information is collected at the Consent visit (#1): 
 
-Demographics: Although this is a small pilot study, demographic questions are relevant to characterize 
the overall participant sample when reporting data. This information is for the purpose of recognizing 
potential limitations of our recruited study group (e.g. our ability to extend the results to other groups).  
These items (“SES Survey” in CATS) were inspired based on the NIH-NIA CROMS system template for 
clinical trials and standard NIH-funded race/ethnicity questionnaire (“Race and Ethnicity Survey”) with 
some adjustments (for example: included is an income question to reflect the overall sample’s financial 
SES for this small sample size study, selected rather than the income amount brackets otherwise 
typically included in similar surveys for larger studies).  
 
-Health History: This survey includes items considered by the Investigators to be minimally sufficient 
context for interpreting a particular participant’s sleep data and the potential relatedness of study 
events to the intervention. Some responses also prompt consenting team members to ask relevant 
probing questions that assess participant readiness for participation/scheduling. This also includes 
potentially relevant sleeping behavior covariates for exploration, such as sleeping position. 
 
 

 
 
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2.0 
Background  
 
 
2.1 
Study Rationale 
 
 
Studying the relationship between sleep and health is important to understand how we might optimize 
sleep to the benefit of our overall mental and physical well-being.  
 
Normal healthy sleep is generally categorized as the absence of sleep disturbances and disorders, but it 
also involves obtaining sufficient duration, good quality, and appropriate timing.8 Insufficient or poor 
sleep results in a greater risk for adverse health outcomes and complication, and also has been 
associated with increased mortality rates and diminished quality of life.9 Therefore, sleep is associated 
with overall well-being and is necessary for health maintenance. This pilot intervention is expected to 
provide evidence for the feasibility and efficacy of a sleep-enhancing intervention that generates and 
systematically applies magnetic field potentials to a sleeper’s environment. The exact mechanism of this 
intervention is not yet understood. 
 
Insufficient sleep, as well as the negative affect and perceived stress that tend to co-occur with poor 
sleep, have all been linked with higher levels of peripheral inflammation12,13. A preponderance of work 
investigating links between sleep and inflammation is focused on adverse effects of sleep disruption; 
here, we hope to focus on whether changes can be effected by sleep improvement, and specifically by 
sleep improvement via this unique intervention type (non-invasive, unobtrusive electromagnetic field 
potential). 
 
3.0 
Inclusion and Exclusion Criteria 
 
3.1 
Inclusion Criteria 
 
1. Written informed consent is obtained from the subject.  
2. Subject is an English speaker and reader. They are able to understand the procedures related to the 
study.  
3. Subject is 40-65 years of age at enrollment 
a. By self-report at Screening & verified with photo ID at full Consent 
4. Subject is not engaged in rotating or nocturnal shift employment 
a. By self-report at Screening 
5. Subject is living independently 
a. By self-report and/or according to their status at a community living facility 
6. Subject’s personal residence is equipped with functional WiFi and subject is willing to permit study 
device connection to their WiFi 
a. By self-report at Screening 
7. Insomnia Severity Index score of ≥8 at enrollment 
a. Based on self-administration at screening 
8. Willing to refrain from initiating new, sleep-directed interventions (e.g. medication; behavioral) that 
are not a part of this study protocol for the duration of study participation 
a. By self-report 
9. Willing to refrain from all nicotine use for the duration of participation 
a. By self-report 

 
 
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10. Willing to refrain from pet access to the bed or sleeping space for the duration of participation (by 
self-report) 
11. Regularly sleeping on a non-water bed 
a. By self-report 
12. Has and uses own smart phone or tablet device, and is willing to continue to use personal device 
daily for study purposes 
a. By self-report 
 
3.1.1 
Does this research involve collecting data from individuals residing outside of the US? 
  No 
 Yes – identify the countries where data collection will take place 
Not Applicable 
 
3.2 
Exclusion Criteria 
 
1. Diagnosed with a sleep disorder 
a. By self-report 
2. Has an implanted medical device (e.g., pacemaker, cochlear) 
a. By self-report 
3. Diagnosed serious mental/neurologic health disorder or substance use disorder 
a. E.g., autism, psychosis, depression/bipolar, dementia 
b. By self-report 
4. Personal health history of epilepsy or traumatic brain injury 
a. By self-report 
5. Taking any physician-directed pharmacologic intervention for sleep or actively engaged in a 
clinically-validated course of therapy (including behavioral therapy for sleep) 
a. By self-report 
6. Diagnosed with hydration problems, or taking prescribed diuretic medication(s). 
a. By self-report 
7. Pregnant, breast-feeding, or planning to become pregnant during the study participation period 
a. By self-report 
8. History of negative reaction to acupuncture. 
a. By self-report 
9. Recreational use of illicit substances in the past month 
a. E.g., marijuana, cocaine, amphetamines, depressants, hallucinogens (LSD, PCP, mushrooms), 
narcotics (heroin/opiates) 
b. By self-report 
10. Any nicotine use in the past 3 months 
a. By self-report 
11. History of sensitivity to, or considers oneself to be uniquely sensitive to, radiofrequency 
a. E.g., discomfort when in physical proximity to radio-emitting objects, such as cell towers or 
modems 
b. By self-report 
12. Was previously engaged in this research as a randomized participant 
13. If a participant does not live within a reasonable commutable distance from the PSU-UP campus (i.e. 
~20min) to accommodate off-site study visits, then they must be willing to accept the costs and 
responsibilities of coming to campus (15-17 visits) in order to participate 
a. By self-report 
 
 

 
 
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3.3 
Early Withdrawal of Subjects 
 
3.3.1 
Criteria for removal from study 
 
Subjects may withdraw their consent to participate in the study at any time for any reason.  
 
Researchers may withdraw subjects from participation at any time at their discretion, regardless 
of participant desire to proceed. Reasons for researcher-determined withdrawal of subjects may 
include: 
 
1. Discovery that a participant meets any exclusion criterion 
2. Subject is unable or unwilling to adhere to protocol requirements, including reasonable 
scheduling timeline and/or commitments noted in Inclusion Criteria. Specifically: 
a. Initiating a new, sleep-directed intervention (e.g. medication; behavioral) that is 
not a part of this study protocol during the course of study participation will 
warrant withdrawal of subjects by researchers (consistent with Inclusion 
Criteria). Adherence will be determined by intermittent participant self-report 
on study surveys. 
3. Apparent or suspected safety reasons 
4. Inability of the research team to conduct the protocol (e.g., technical or power failure) 
 
3.3.2 
Follow-up for withdrawn subjects 
 
Safety data would be necessary with early withdrawal only in the case of an adverse event. 
Participants who withdraw from the study prior to completion and who were already 
randomized at the time of their withdrawal will be offered a survey similar to those completing 
the study to assess both their awareness of their assigned condition order and so that they have 
the opportunity to request to be contacted with information about their randomized order after 
the study concludes (please refer to CATS attachment, “End of Study Survey”). Study 
participants who withdraw early from the study will also be offered the same optional Follow-
Up survey that is offered to completed participants. 
 
Study participants who withdraw early from the study may or may not be eligible to participate 
again at a later time, depending on the reason for, and timing of, early withdrawal. 
 
There are not any known risks to participants related to truncation of the study intervention 
(sleep pad use) in excess of those present prior to participation. 
 
4.0 
Recruitment Methods 
 
4.1 
Identification of subjects 
 
Participants may be identified and recruited directly by several means. Flyers (please refer to CATS 
attachment) in the Penn State University Park and Centre County region at cooperating 
businesses/organizations/facilities will be the primary recruitment method, targeting participants in the 
central-Pennsylvania region. Additional potential recruitment methods include: word of mouth, web-
based advertisements (including social media, e-flyers, or similar virtual communications’ please refer to 
CATS attachment “Other Electronic Recruitment”), emails through relevant Penn State University 
listservs, online participant recruitment platforms (e.g., StudyFinder, ResearchMatch, ActivePALS), news 
stories about the Investigators’ laboratories and their research, and/or direct contact from a repository 

 
 
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of previous research participants who indicated interest in future research participation (using contact 
information that they provided at that time, please refer to CATS attachment: Direct Recruitment 
Email”).  
 
4.2 
Recruitment process 
 
4.2.1 
How potential subjects will be recruited. 
 
A link to complete the screening (which includes a Screening Consent Form, please refer to CATS 
attachments) in REDCap will be included in study promotions where feasible. IRB-approved 
recruitment materials/messages will include contact information (e.g. phone and email) of study 
staff, which interested parties may use to communicate with members of our research team and 
inquire about this study. A study-dedicated PSU email account that is password-protected with 
2-factor authentication (sleeppad@psu.edu) will be established for use in such communications. 
 
Social media accounts dedicated to this research may be created for recruitment, and 
researchers will also have the option to re-post/share/tweet/forward and otherwise promote 
advertising post(s) from their own personal social media accounts. Advertising post(s) will be 
consistent with approved electronic recruitment language (please refer to CATS attachment, 
“Electronic Recruitment Language”) and flyers. 
 
Interested individuals are directed to complete electronic screening in REDCap and, if eligible, to 
provide their contact information for use in scheduling an appointment for completing in-person 
screening qualification activities and Informed Research Consent at a later time. 
 
4.2.2 
Where potential subjects will be recruited. 
 
Potential participants will be recruited electronically (email, ListServs, social media), in the 
location(s) of posted flyers (local to the PSU-UP campus), by word-of-mouth, and/or directly 
(e.g., email); none of these recruitment avenues are bound to a particular physical location. 
 
Study volunteers may encounter the individual contact information of study team members 
inadvertently elsewhere (e.g., on the university profile pages). In instances of potential 
volunteers or participants contacting study team members outside the designated email 
account, those individuals will be redirected to use the dedicated study email account for study-
related messaging.  
 
4.2.3 
When potential subjects will be recruited. 
 
Potential participants will be recruited as soon as feasible after IRB approval. Recruitment will 
continue until the target sample size (n=10) reaches randomization. Participant dropout prior to 
study completion will warrant recruitment of replacement participants up to the target. 
 
4.2.4 
Describe the eligibility screening process. Screening begins when the investigator obtains 
information about or from a prospective participant in order to determine their eligibility.   
  Eligibility screening is occurring before consent* - describe the process below  
  Eligibility screening is occurring after consent - describe the process below 
  Eligibility screening is occurring, consent is not being obtained in this research - describe the 
process below 

 
 
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  Not applicable - Eligibility screening is not being done in this research 
 
Consent will occur in 2 phases. Eligibility screening will happen after an electronic Screening 
Consent Form has been completed by the subject in the REDCap system. Qualification according 
to Inclusion and Exclusion Criteria will occur as a part of this eligibility screening survey (please 
refer to “Screening Survey” in CATS attachments). Participants are informed of and agree to 
scheduling & attending an initial study visit where completion of the Informed Research Consent 
Form occurs (please refer to “Informed Research Consent” in CATS attachments) and data 
collection begins. Information from eligibility screening may be used and reported as study data. 
 
In some studies, these procedures may not take place unless HIPAA Authorization is obtained OR a 
waiver of HIPAA Authorization when applicable for the screening procedures is approved by the IRB. 
 
*Unless informed consent is waived by the IRB, screening before consent is only permitted when 
screening activities are limited to the collection of information through oral or written communication 
OR when identifiable private information or identifiable biospecimens is obtained by accessing records 
or stored identifiable biospecimens. Screening before consent is not permitted if data will be used for 
activities other than eligibility screening/recruitment (e.g., data analysis).  
   
5.0 
Consent Process and Documentation  
 
5.1 
Consent Process: 
 
Check all applicable boxes below: 
 Informed consent will be sought and documented with a written consent form [Complete Sections 
5.2 and 5.6; If this is the only box checked, mark Sections 5.3, 5.4 and 5.5 as ‘Not applicable’]  
 
 
 Implied or verbal consent will be obtained – subjects will not sign a consent form (waiver of 
written documentation of consent) [Complete Sections 5.2, 5.3 and 5.6; If this is the only box 
checked, mark Sections 5.4 and 5.5 as ‘Not applicable’]  
 
  Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception). [Complete section 5.2, 5.4 and 5.6; If this is the only box checked, mark 
Section 5.5 as ‘Not applicable’]  
 
 Informed consent will not be obtained – request to completely waive the informed consent 
requirement. [Complete Section 5.5; If this is the only box checked, mark Sections 5.2, 5.3, 5.4 and 
5.6 as ‘Not applicable’] 
 
5.2 
Obtaining Informed Consent  
5.2.1 
Consent Process  
 
 
An individual accessing the REDcap screening survey (for study qualification) is first presented 
with an electronic version of the Screening Consent form. A check-box option to proceed to the 
survey, indicating implied consent for the screening procedure, is required in REDCap before 
advancing to the survey. Screening consent is not associated with a particular location, although 
the Screening Consent form indicates that survey questions may be sensitive in nature 

 
 
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(therefore it is at the discretion of an individual to proceed if accessing the electronic survey in a 
public setting). 
 
After completing the electronic screening process, qualifying participants will schedule an in-
person Informed Research Consent appointment with an IRB-approved study team member 
who is designated as “involved in consent” in the CATS IRB system. Participants may review the 
consent form in advance, and will be encouraged to consult with family, friends, their PCP, or 
anyone else that they may wish to consult before deciding whether to participate. 
 
Informed Research Consent may be completed in the participant’s personal residence, in a 
private area of a participant’s community living facility, or in the laboratory space of the PI on 
the PSU-UP campus. A qualified study team member will inform the subject of all study 
requirements before the subject decides whether or not to participate. Participants will be able 
to review the consent document and address questions or concerns prior to completing the 
form (either hard-copy or electronically in the REDCap system). Study coordinators, the Principal 
Investigator, and other study staff will engage in the ongoing process of informing subjects 
about study conditions and other information that will inform their decision about whether or 
not to continue participating. Participants will be offered a copy (electronic or physical) of the 
Informed Research Consent for their records. 
 
The study team member will also sign to indicate having conducted consent with a given 
subject/ID.  
 
In the event that a study volunteer elects to take more time to consider participation before 
choosing to proceed with the Informed Research Consent at their appointment, study staff will 
attempt to maintain contact with the study volunteer until such time as the volunteer decides to 
either schedule another appointment for Informed Research Consent completion or to 
withdraw. 
 
5.2.2 
Coercion or Undue Influence during Consent  
 
It is stated in the Screening and Informed Research Consent Forms that participation in this 
research is completely voluntary, that not being involved does not have any negative 
consequences, and that participants may withdraw from the study or their consent at any time 
without repercussions to them. 
 
5.3 
Waiver of Written Documentation of Consent  
 
 
 
 
5.3.1 
Indicate which of the following conditions applies to this research: 
  The research presents no more that minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
 
OR 
 
  The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 
will be asked whether the subject wants documentation linking the subject with the research, 
and the subject’s wishes will govern. (Note: This condition is not applicable for FDA-regulated 
research. If this category is chosen, include copies of a consent form and /or parental 

 
 
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permission form for participants who want written documentation linking them to the 
research.) 
 
OR 
 
  If the subjects or legally authorized representatives are members of a distinct cultural group 
or community in which signing forms is not the norm, that the research presents no more 
than minimal risk of harm to subjects and provided there is an appropriate alternative 
mechanism for documenting that informed consent was obtained.  (Note: This condition is not 
applicable for FDA-regulated research.)  
 
For distinct cultural groups describe the alternative mechanism for documenting that 
informed consent was obtained: 
 
5.3.2 
Indicate what materials, if any, will be used to inform potential subjects about the 
research (e.g., a letter accompanying a questionnaire, verbal script, or implied consent 
form) 
 
 The HRP-585 Screening Consent template is used to sufficiently inform potential subjects about 
the research. 
 
 
 
5.4 
Consent – Other Considerations  
 
5.4.1 
Non-English-Speaking Subjects 
 
Non-English speakers will not be enrolled in the study. 
 
5.4.2 
Cognitively Impaired Adults 
 
5.6.2.1 Capability of Providing Consent 
 
Subjects who are independent living and indicate both a physical and cognitive 
capability of self-care will be eligible to participate in the study. Participants will 
initially self-attest to these criteria on a screening qualification survey and will be 
further screened by a research team member at full consent. The enrollment 
population age range in this research is unlikely to present issues related to 
cognitive decline/MCI.  
 
5.6.2.2 Adults Unable to Consent 
 
Not applicable; those who cannot provide their own informed consent will not be 
enrolled in the study. 
 
5.6.2.3 Assent of Adults Unable to Consent 
 
Not applicable; those who cannot provide their own informed consent will not be 
enrolled in the study. 
 

 
 
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5.4.3 
Subjects who are not yet adults (infants, children, teenagers)  
 
5.6.3.1 Parental Permission 
 
Not applicable; subjects must be 40-65 years of age. 
 
5.6.3.2 Assent of subjects who are not yet adults 
 
Not applicable; subjects must be 40-65 years of age. 
 
6.0 
Study Design and Procedures 
 
6.1 
Study Design 
 
This 8-week, randomized, cross-over, at-home clinical trial of mid-life adults (men and women aged 40-
65 years) consists of four segments: Baseline (week 1), active Intervention/Control (weeks 2-4), 
Washout (week 5), and active Intervention/Control (weeks 6-8).   
 
6.2 
Study Procedures 
 
 
General overview 
 
Participants complete Screening Consent in REDCap and, if eligible based on screening surveys, schedule 
their consent appointment and study dates. 
 
Participants complete an Informed Research Consent in-person with study staff. Participation in the 
~8wk study begins immediately after completion of this consent. 
 
Throughout the entire ~8wk study: 
-Ambulatory sleep measurement (via wrist-worn actigraphy, day and night ~24hrs) 
-Twice daily self-assessment of sleep, related activities, and device usage (via REDCap sleep diaries 
[~1min each, totaling ~2min daily]) administered in the morning (“Morning” survey in CATS) and evening 
(“Bedtime” survey in CATS) 
-Weekly REDCap surveys (participants receive survey link at either/both their personal email or phone 
number [by text message], according to their preference; ~15min each). Participants may choose to 
receive email or text message reminders, or phone/voicemail reminders, to their personal 
accounts/devices about surveys 
-Responding to questions by staff during each study visit to determine ongoing qualification and possible 
study events 
 
Overview of 4 study parts (details in below, specific sections): 
 
-“Baseline”: Baseline data collection without sleep pad device present/in-use (week ~1) and 
randomization. Objective sleep monitoring for 2 nights. Blood sample (up to 40cc / up to 3 tablespoons) 
collected. 
 
-“Phase 1”: Active intervention/control with either the sleep pad or an identical-looking/operated 
‘sham’ pad present/in-use nightly (weeks ~2-4). Objective sleep monitoring for 2 nights. Blood sample 
(up to 40cc / up to 3 tablespoons) collected. 

 
 
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-“Washout”: Break from presence/use of the sleep pad device (week ~5) 
 
-“Phase 2”: Active intervention/control with either the sleep pad or an identical-looking/operated 
‘sham’ pad present/in-use nightly (weeks ~6-8). Objective sleep monitoring for 2 nights. Blood sample 
(up to 40cc / up to 3 tablespoons) collected. 
 
All participants will complete all parts of the study (i.e. both intervention and control) but the order in 
which they experience these conditions will be randomized at the end of Baseline week after verifying 
compliance with study procedures and eligibility to continue.  
 
All visits may take place in either a participant’s personal residence or privately at the PSU-UP campus, 
excepting for participants whose distance from campus is too great for staff commute (i.e., more than 
about 20min one-way). In those cases, participants must come to the PSU-UP campus for study visits.   
 
Specific study procedures 
 
Polysomnography (PSG): A cluster of measures acquired by bioelectrically-sensitive sensors that include 
EEG (neurocortical field potentials), EOG (ocular muscle), EMG (chin), and EKG (cardiac activity). Surface 
(non-invasive) electrodes will be applied to specific locations on the subject's face, head, and chest using 
temporary adhesives that are designed for clinical use on humans. Our sleep monitoring system permits 
ambulatory collection via a portable amplifier worn/carried as participants go about their regular 
activities, with the exception of bathing. 
 
Actigraphy: Activity-sensitive wrist-worn ambulatory device that is non-invasive. Records signals 
pertaining to motion activity and light exposure. An “on-wrist detection” feature permits compliance 
verification on devices to determine valid recordings.  
 
Surveys: 
Insomnia Severity Index (ISI) - The ISI assesses perceived severity of insomnia. The ISI has an internal 
consistency alpha coefficient of 0.74, and has shown convergent validity with other measures such as 
the Pittsburgh Sleep Quality Index (r = 0.67), the Dysfunctional Beliefs and Attitudes about Sleep (r = 
0.55), and sleep diaries (range from 0.32-0.91).10, 11 
PROMIS Pain Intensity and Interference (PI&I) – The PI&I assesses retrospective average weekly pain 
both in terms of severity and functionality. Intensity: A weekly self-report quantifying pain on a visual 
analog scale. Interference: A weekly self-report on a visual analog scale of whether and how much pain 
interfered with typical daily experiences. Responses to these exploratory surveys are expected to 
change (improve) as a function of sleep (improvement).14 
 
6.2.1 
Visit 1 - Informed Research Consent and Baseline Start 
 
Informed Research Consent and study initiation (including and initial intake survey [please refer 
to CATS attachments “Race/Ethnicity Survey,” “Socioeconomic Survey,” and “Health History 
Survey”] and collection of payment information (consistent with PSU tax reporting 
requirements) will take about 1hr to complete. Upon completion: 
 
-Participants receive instruction regarding, and begin data collection with, ambulatory activity 
(actigraphy) monitor  
-Participants are equipped with abbreviated Polysomnography (PSG) monitoring equipment and 
recording is initiated 

 
 
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Above procedures after Consent take about 1 hour to complete. 
 
-Participants may return home (if applicable) and are continuously monitored throughout the 
subsequent remaining day and overnight with PSG 
 
6.2.2 
Visit 2 (Baseline) 
Study team members visit the participant the following morning to remove PSG. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
 
6.2.3 
Visit 3 (Baseline) 
After at least one overnight without PSG, another participant visit occurs. 
 
-Actigraphy device is exchanged (for later compliance evaluation). 
-Participant is re-equipped with abbreviated PSG and recording is initiated 
-Participants return home (if applicable) and are continuously monitored throughout the 
subsequent remaining day and overnight with PSG 
 
Above procedures take about 1hr ‘active’ engagement to complete. 
 
 
6.2.4 
Visit 4 (Baseline) 
 
Study team members visit the participant the following morning to remove PSG. 
 
-Participants whose actigraphy data evidence compliance and with at least one successful 
overnight PSG monitoring proceed in the study. Participants whose activity data suggest 
noncompliance or who experience technical failure of either actigraphy or PSG during the first 
study week may have the option (at researcher discretion) to repeat their first week of study 
activities up to this point without additional compensation. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.5 
Visit 5 (Baseline) 
Participant has a fasted (~8hrs immediately preceding the appointment, no food and limited 
water intake) blood draw conducted by qualified Clinical Research Center (CRC; Noll Laboratory) 
staff.  
 
-Participant completes weekly REDCap surveys 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.6 
Visit 6 (Baseline) 
Qualifying participants are randomized to an order of study conditions upon completion of this 
visit. 
 

 
 
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-Participant receives the Frequen-ZZZ sleep pad device or sham device (consistent with their 
randomization order; participant will not be informed of their assignment) and is trained on its 
setup/use 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.7 
Visit 7 - Phase I Start: Intervention or Control 
 
Near the end of the 3rd study week, participants have an in-person study visit to be equipped 
with abbreviated PSG monitoring. Overnight recording is initiated. 
 
Above procedures take about 1 hour ‘active’ engagement to complete. 
 
-Participant returns home (if applicable) and is continuously monitored throughout the 
subsequent remaining day and overnight with PSG 
 
6.2.8 
Visit 8 (Phase I) 
Study team members visit the participant the following morning to remove PSG. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.9 
Visit 9 (Phase I) 
 
Near the end of the 4th study week, participant is re-equipped with abbreviated PSG. Overnight 
recording is initiated. 
 
Above procedures take about 1hr ‘active’ engagement to complete. 
 
-Participant returns home (if applicable) and is continuously monitored throughout the 
subsequent remaining day and overnight with PSG 
 
 
6.2.10 Visit 10 (Phase I) 
 
Study team members visit the participant the following morning to remove PSG. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.11 Visit 11 (Phase I) 
 
Participant has a fasted blood draw conducted by qualified Clinical Research Center (CRC; Noll 
Laboratory) staff. This visit (11) may be combined with the previous visit (10) if a participant 
elects for the blood draw to occur in their personal residence. 
 
-Participant returns the bedside controller. 
-Participants keep the bed pad portion of the sleep pad system for re-use later in the study. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
6.2.12 Washout and Visit 12 
 

 
 
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The ~5th study week will consist of a “washout” during which no participants use the functional 
features of sleep pad system. However, throughout this week, participants do continue 24hr 
actigraphy monitoring, continue to complete daily sleep diary and device usage survey entries 
(~2min combined), and continue to complete the weekly REDCap survey all noted in the general 
summary above. 
 
Note that an optional pause of study activities at the conclusion of the Washout week will be 
available. Participants are not required to continue passive (actigraphy) monitoring or surveys 
during any pause period (>1wk). Maximum duration of appropriate pause will be determined by 
Co-Investigators, but is not anticipated to exceed 10wks. 
 
Total anticipated Washout active study time commitment is 30min. 
 
At the beginning of study week 6, a participant receives again for use the bedside controller, 
either by delivery (in-person or by mail) or pickup from PSU-UP campus. Because receipt may 
occur in person, this is considered the “12th visit” although not necessarily requiring a “visit”. 
 
6.2.13 Visit 13 – Phase 2 Start: Intervention or Control 
 
Near the end of the 7th study week, participants have an in-person study visit to be equipped 
with abbreviated PSG monitoring. Overnight recording is initiated. 
 
Above procedures take about 1 hour ‘active’ engagement to complete. 
 
-Participant returns home (if applicable) and is continuously monitored throughout the 
subsequent remaining day and overnight with PSG 
 
6.2.14 Visit 14 (Phase 2) 
 
Study team members visit the participant the following morning to remove PSG. 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
 
6.2.15 Visit 15 (Phase 2) 
Near the end of the 8th study week, participant is re-equipped with abbreviated PSG. Overnight 
recording is initiated. 
 
Above procedures take about 1hr ‘active’ engagement to complete. 
 
-Participants returns home (if applicable) and is continuously monitored throughout the 
subsequent remaining day and overnight with PSG. 
 
6.2.16 Visit 16 (Phase 2) 
 
Study team members visit the participant the following morning to remove PSG. 
 
-Participant returns sleep pad system (including pad and controller). 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 

 
 
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6.2.17 Visit 17 (Phase 2) 
 
Participant has a fasted blood draw conducted by qualified Clinical Research Center (CRC; Noll 
Laboratory) staff. This visit (17) may be combined with the previous visit (16) if a participant 
elects for the blood draw to occur in their personal residence. 
 
Upon completion, participants receive a ~1min survey to assess both their awareness of their 
assigned condition order and so that they have the opportunity to request to be contacted with 
information about their randomized order after the study concludes (please refer to CATS 
attachment, “End of Study Survey”). Participants also receive an optional ~1min survey via email 
that is administered through REDCap shortly after ending participation (please refer to CATS 
attachment, “Follow-Up Survey”). 
 
Above procedures take about 30min ‘active’ engagement to complete. 
 
 
6.3 
Duration of Participation 
 
Screening Consent activities are expected to take about 30min to complete (including initial remote 
electronic survey and in-person activities at the first study visit). One session expected (secondary 
screening), with another session optional (if not qualifying on abbreviated MoCA). 
 
Consent activities are expected to take about 1hr to complete. One session is expected, with additional 
optional session(s) if a participant decides they want more time to consider during a session. 
 
Overall study timeline after Consent concludes is approximately 8wks. During those 8wks, active study 
engagement by a participant is expected to take about 15hrs, with an expected 17 in-person sessions. 
That time is spread out across study parts in about the following distribution: 
 
Baseline (week ~1): ~4.5hrs with 6 sessions (visits 1-6 above) including surveys 
Part 1 (weeks ~2-4): ~5hrs (weighted towards weeks 3 & 4) with 5 sessions (visits 7-11 above) including 
surveys 
Washout (week ~5): ~30min with 1 session (visit 12 above) including surveys 
Part 2 (weeks ~6-8): ~5hrs (weighted towards weeks 7 & 8) with 5 sessions (visits 13-17 above) including 
surveys 
 
6.4 
Test Article(s) (Study Drug(s) and/or Study Device(s)) 
 
6.4.1 
Description 
 
The test article in this study is an investigational device. The pad portion is designed to be placed 
onto a bed beneath a fitted sheet in a specific orientation relative to a pillow and slept upon. 
The pad is powered with an attached bedside device, applies a safe range of magnetic waves. 
The stimulation is hypothesized to improve sleep duration and quality. 
 
The Sleep Pad system has undergone preliminary review by the FDA (please refer to CATS 
attachment, “FDA Review Meeting Minutes”) and received enthusiasm for empirical evaluation 
in this particular protocol as an intervention. According to published FDA device categorization 
guidelines (please refer to CATS attachment, “FDA Risk Categorization Guidelines,” particularly 
pg.3 after title pg.) and in light of electromagnetic safety data (please refer to CATS 

 
 
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attachments, “Electromagnetic Field Safety Testing” and “FCC Compliance Test Statement”), this 
study’s PI considers the Sleep Pad system to be Not of Significant Risk (NSR). The device should 
not be used with powered covers (e.g. heating pads) nor on water beds, although there are not 
known risks to doing so. Other radiofrequency signals in the sleeper’s environment may 
overpower/wash-out the low level magnetic field generated by the pad, so it is recommended 
to turn off or remove any modem/router located in the bedroom and to put cellular devices into 
airplane or Do Not Disturb mode during Sleep Pad system use for optimal effect, although there 
are not known risks to having such devices in use with the Sleep Pad. 
 
6.4.2 
Treatment Regimen 
 
Treatment dosing is under participant control, by physical proximity/orientation to the pad 
portion of the Sleep Pad system, and by a manually operated power button on the bedside 
controller portion of the Sleep Pad system. Dosing is scheduled to occur throughout the 
participant’s typical nocturnal sleep period, nightly during the Intervention (either phase I or 
phase II, depending upon randomization) of the research. The range will be preset to the 
minimum setting by researchers, and participants will be instructed to not change the settings. 
Participants verify their “dose” settings by attesting to not having changed settings 
implemented by researchers in nightly REDCap surveys. 
 
6.4.3 
Method for Assigning Subject to Treatment Groups 
 
All participants in this study will experience all study conditions (i.e. a sham (Control) and an 
active (Intervention) Sleep Pad bedside controller), in a randomized crossover design. The 
random assignment to intervention order (Sham Sleep Pad System vs. Activated Sleep Pad 
System at Part 1; reverse at Part 2) will be completed in REDCap, with replacement for early 
withdrawal, and intention to assign 50% of participants to each study condition order. 
Participant recruitment will not be stratified, but randomization to a study condition order will 
be gender-stratified to ensure balanced assignment of males and females (assigned at birth) 
between condition orders. 
 
Dr. Orfeu M. Buxton is the designated team member who will implement and hold the blind 
related to these randomization procedures; he does not interact directly with participants. Once 
randomized, an appropriate Sleep Pad controller ID is designated for use and shared with 
blinded study team members. The linking list of controller IDs and their settings (activated vs 
deactivated) is confidentially maintained by the Sponsor and Dr. Buxton unless specific study 
events require lifting the blind. 
 
6.4.4 
Subject Compliance Monitoring 
 
Participants will complete nightly REDCap surveys self-attesting adherence to the protocol 
during Control/Intervention (Phases 1 & 2) that are shared with the research team as data to 
confirm Sleep Pad use.  
 
6.4.5 
Blinding of the Test Article 
 
This study is a double-blind trial, in which bedside controllers for Sleep Pad systems are coded 
and either “activated” or “deactivated” (sham) by the manufacturer prior to receipt (in two sets) 
for use in the research. A “deactivated” bedside controller retains all functionality (and evidence 
of functionality) of an “activated” bedside controller, excepting the stimulation. The blind is 

 
 
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maintained by a designated study team member who will have access to the list linking device 
code IDs to their relative active/sham group, and who does not have interaction with study 
participants. This blind will be lifted if relevant for safety reasons in cases of serious adverse 
event on a participant case-by-case basis, and on the whole for other researchers after 
completion of the entire trial for data analysis. 
 
6.4.6 
Receiving, Storage, Dispensing and Return  
 
6.4.6.1 
Receipt of Test Article  
 
The pad portion of the Sleep Pad system is interchangeable, so a 
participant will receive and use only one throughout their study. 
Participants receive two different bedside pad controllers during the 
course of the study, one at a time; once each for Phase 1 and Phase 2 
(Control/Intervention). The bedside controller device code corresponding 
to a given participant ID and Phase will be documented for later data 
analysis. Participants receive in-person instruction regarding Sleep Pad 
system setup upon receipt, and also print and/or electronic instructional 
materials. 
 
6.4.6.2 
Storage 
 
The pad portion of the Sleep Pad system is interchangeable between 
bedside controllers and can only be “used” (i.e. apply magnetic field) when 
equipped with a corresponding “activated” bedside controller . Bedside 
controllers will be stored in the laboratory space and code-labeled 
according to their internal settings (i.e. one set with codes corresponding 
to “activated” and one set with codes corresponding to “deactivated,” but 
to which all Investigators except one are blinded). Pad portions of the 
Sleep Pad system will be stored separately from bedside controllers until 
being provided to a study participant. Participants maintain the “pad” 
portion of the Sleep Pad system throughout the study. Participants will be 
instructed that only research participants in the study should use the 
device as directed, and that no individual should attempt to use the device 
inconsistent with directions. a person in physical proximity to the pad is not 
expected to have any “exposure” to its signal unless it is used as directed. 
 
6.4.6.3 
Preparation and Dispensing 
 
Participants will be randomly assigned to their crossover order (i.e. to their 
order of using an “activated” or a “deactivated” bedside controller). 
Activation or deactivation and coded device ID(s) are applied to the 
bedside controller portion of the Sleep Pad system by the manufacturer, 
prior to receipt by researchers. Researchers receive coded controllers. A 
list linking device IDs to their settings, and thereby the blind, is maintained 
by a designated study team member. “Administration” of the Sleep Pad 
system occurs when a participant lays upon the pad portion of a system 
that includes an activated bedside controller, which they have turned on 
manually, consistent with contact/orientation instructions (as designated 
in setup instructions). 

 
 
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6.4.6.4 
Return or Destruction of the Test Article 
 
The Sleep Pad systems (bedside controller devices [used or unused] and 
pad portions) will be returned (i.e. shipped) to the Sponsor/manufacturer 
at the conclusion of the study. 
 
6.4.6.5 
Prior and Concomitant Therapy 
 
Participants must be willing to refrain from initiating new, sleep-directed 
interventions (e.g. medication; behavioral) that are not a part of this study 
protocol for the duration of study participation. Taking any physician-
directed pharmacologic intervention for sleep or being actively engaged in 
a clinically-validated course of therapy (including behavioral therapy for 
sleep) is an exclusion criterion. 
 
7.0 
Number of Subjects and Statistical Plan 
 
7.1 
Number of Subjects 
 
We expect to evaluate up to 35 participants in screening qualification, aiming to initially identify up to 
20 eligible individuals according to the screening procedures. Screening evaluations will pause at that 
time by pausing both the REDCap survey availability and by our otherwise manual control of release of 
the screening survey REDCap link until it is determined by Investigators that additional recruitment is 
necessary (e.g. to replace participant drop-outs or if failure to identify 20 eligible individuals occurs). 
Should recruitment need to be re-opened beyond 35 participants an IRB Protocol modification would 
occur, expecting to regulate future screening qualification in specific intervals to reduce risk of 
unnecessary screening of individuals. We aim to complete 10 subjects in this study. 
 
7.2 
Sample Size Determination 
 
This pilot study is being used to determine feasibility and effect sizes, therefore no information is 
available upon which to estimate a minimum necessary sample size. This study will inform the sample 
size of future studies and proposals. 
 
7.3 
Statistical or Analytic Methods 
 
Primary and secondary outcomes will be compared between sleep pad conditions, within participants, 
as a change score relative to their own Baseline. 
 
 
8.0 
Risks 
 
PSG and ambulatory (actigraphy) monitoring devices are typical clinical outpatient procedures that pose mild risks 
that include but are not limited to: the attachment and removal of monitoring electrodes may cause mild, 
temporary discomfort; participants may have difficulty sleeping while the monitoring equipment is attached; 
participants may experience mild frustration maneuvering around equipped devices; location where sensors are 
worn or applied may experience temporary skin irritation. It is possible that wearing monitoring equipment may 
be bothersome enough to interfere with sleep quality (although that is not an intended purpose of any 
monitor/intervention in this research), which could make subjects feel irritable or more tired during the day time. 

 
 
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To minimize these risks, we thoroughly clean devices between subjects, spread out overnights involving PSG, and 
can adjust the application site of some sensors as-needed based on reported subject comfort/reactivity.  
 
Participants may feel uncomfortable answering some survey questions. Participants may elect to not answer any 
survey question that they do not want to, but not answering may affect their study eligibility to initiate or 
continue in the study, or to be included in research data analyses. 
 
Blood draws often cause mild pain, swelling or bleeding. Fasting before blood draws may be uncomfortable. There 
may be some bruising (blood under the surface of the skin), which can be minimized by pressing on the site after 
the needle is removed. There is also a small chance of infection, dizziness, or fainting. These risks will be 
minimized, and most likely eliminated, by having trained CRC staff perform the blood draw on a seated or reclined 
participant using sterile supplies. If dizziness or fainting occurs, the symptoms will be alleviated by closely 
monitoring the participant, directing them to lie flat with their feet raised, and by offering a snack and/or 
beverage. Participants demonstrating these symptoms may be asked to stay at the blood draw location (i.e. PSU 
CRC) or to permit study staff to stay at the blood draw location (i.e. in their personal residence) until staff have 
confirmed that the participant is well enough. 
   
Use of the Frequen-ZZZ Sleep Pad may cause perceived warmth (although the pad does not emit heat) that may 
affect sleep. If sleep is successfully deepened by Sleep Pad system use, a device user may experience temporary 
drowsiness, dizziness, or disorientation upon awakening from deeper sleep (called sleep “inertia”). There is a risk 
of fall resulting from these sensations. To mitigate this risk, participants will be encouraged to complete their 
Morning Survey on their phone prior to getting out of bed in the morning, to encourage time for these possible 
sensations to pass. Participants will also be encouraged to take care if getting out of bed after awakening during 
the night. Participants are instructed on the optional procedure to pause the Sleep Pad controller during nocturnal 
awakenings, and this procedure is included in their Quick Reference Guide; this also should facilitate time/care 
taken upon awakening from Sleep Pad use. 
 
Although it is rare, improper use of the Frequen-ZZZ sleep pad may lead to mild negative side effects, including 
headaches for short periods of time, restlessness, nausea, and/or perspiration.  Participants will be instructed on 
proper use of the sleep pad at consent, will be reminded of proper use in-person prior to each 
Intervention/Control study phase, and will be provided with an instructional sheet to take along with them for 
reference at home. The Sleep Pad has undergone testing by F2 Labs and complies with FCC standards for human 
exposure to electromagnetic/radio-frequency emissions and some additional emissions regulations (please refer 
to CATS attachments, “FCC Compliance Test Statement” and “Electromagnetic Field Safety Testing”). The Sleep 
Pad has not be evaluated under certain conditions, and so should not be used together with other powered 
equipment (i.e. heated blankets or similar). The Sleep Pad should not be used on a water bed. 
 
There is a risk of loss of confidentiality if participant information or identity is obtained by someone other than the 
investigators, but precautions will be taken to prevent this from happening. The confidentiality of participant 
electronic data created by participants or by the researchers will be maintained as required by applicable law and 
to the degree permitted by the technology used. Absolute confidentiality cannot be guaranteed. 
9.0 
Adverse Event Reporting 
 
9.1 
Adverse Event Definitions 
 
 
 
For device studies, incorporate the following definitions into the below responses, as written: 

 
 
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Unanticipated 
adverse device 
effect 
Any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or IDE application (including a supplementary plan 
or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
9.2 
Recording of Adverse Events 
• 
 
 
The study procedures involve frequent contact between study staff and participants. Research subjects 
will be routinely questioned about adverse events at such study visits, and relevant responses will be 
documented by study staff. Relevant events will be advanced to the PI consistent with an Event 
Reporting SOP on which staff are trained. The PI determines whether advanced events meet criteria for 
immediate reporting to IRB and maintain documentation of all events for annual IRB reporting. 
 
 All adverse events (serious or non-serious) and abnormal findings observed or reported to study team 
believed to be associated with the study drug(s) or device(s) by the PI will be followed until the event (or 
its sequelae) or the abnormal test finding resolves or stabilizes at a level acceptable to the Investigators. 
Resolution will be documented. 
 
An abnormal finding will be classified as an adverse event if one or more of the following criteria are 
met: 
 
•The finding is accompanied by clinical symptoms 
•The finding necessitates additional diagnostic evaluation(s) or medical/surgical intervention; including 
significant additional concomitant drug treatment or other therapy 
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does not 
constitute an adverse event. 
•The finding leads to discontinuation of subject participation in the clinical research study 
•The finding is considered an adverse event by the Investigators. 
 
An unanticipated adverse device effect will also constitute an “abnormal finding”, defined as: 
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the investigational plan or IDE application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects 
 
9.3 
Causality and Severity Assessments 
 
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event. 
 
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 

 
 
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“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history. 
 
9.4 
Reporting of Adverse Reactions and Unanticipated Problems to the FDA   
 
9.4.1 
Written IND/IDE Safety Reports 
 
The Sponsor-Investigator will submit a completed FDA Form 3500Ato the FDA’s Center for 
Devices and Radiological Health for any observed or volunteered adverse effect that is 
determined to be an unanticipated adverse device effect. A copy of this completed form will be 
provided to all participating sub-investigators. 
 
The completed FDA Form 3500Awill be submitted to the FDA as soon as possible and, in no 
event, later than 10 working days after the Sponsor-Investigator first receives notice of the 
adverse effect. 
 
If the results of the Sponsor-Investigator’s follow-up evaluation show that an adverse effect that 
was initially determined to not constitute an unanticipated adverse device effect does, in fact, 
meet the requirements for reporting; the Sponsor-Investigator will submit a completed FDA 
Form 3500Aas soon as possible, but in no event later than 10 working days, after the 
determination was made. 
 
For each submitted FDA Form 3500A, the Sponsor-Investigator will identify all previously 
submitted reports that that addressed a similar adverse effect experience and will provide an 
analysis of the significance of newly reported adverse effect in light of the previous, similar 
report(s).  
 
Subsequent to the initial submission of a completed FDA Form 3500A, the Sponsor-
Investigator will submit additional information concerning the reported adverse effect as 
requested by the FDA. 
 
9.5 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) experienced 
by a subject or other individual, which in the opinion of the investigator is determined to be (1) 
unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
9.6 
Unblinding Procedures 
 
Unblinding of Investigators prior to the conclusion of data collection is not expected other than for 
safety-related reasons in association with a study adverse event. A team member who does not have a 
role interacting with study participants is designated to maintain the blind for this purpose. Unblinding 
would occur only in cases of “serious” adverse reaction by a participant, in an effort to thoroughly 
report the circumstances of such adverse reaction to the IRB, Sponsor, and likely also to the FDA if 
evaluation for a new risk categorization of the investigational device is determined necessary by the IRB. 
 
9.7 
Stopping Rules 
 

 
 
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Not Applicable: This pilot study involves a small sample size and does not have a defined primary safety 
endpoint. It is considered Minimal Risk by Investigators.  
 
Unanticipated serious adverse events that are clearly related to the study intervention would warrant 
considering discontinuation of the study, and such decisions would be conducted in collaboration with 
the PSU CATS IRB. Study pause or interruption appearing unrelated to the study intervention may occur 
based on participant needs or unexpected events; these would not warrant study stoppage and 
Investigators will work with affected participants on a case-by-case basis to determine appropriateness 
of re-enrolling (if pre-randomization) or continuing again in the study. 
 
10.0 
Study Monitoring, Auditing and Inspecting 
 
10.1 
Study Monitoring Plan  
 
 
10.1.1 Quality Assurance and Quality Control 
 
The Principal Investigator, experienced in conducting HSR clinical trials with Good Clinical 
Practice, will take responsibility for overseeing the study and ensuring that it is in compliance 
with regulatory specifications of the FDA and/or IRB. 
 
The Sponsor will also be involved in the monitoring of study data. The Sponsor will review any 
reports from Investigators of probably- and possibly- device-related study events, and will 
report events determined to be promptly reportable consistent with the FDA’s timeline. 
 
10.1.2 Safety Monitoring 
 
The PI (Chang) will conduct and monitor the study consistent with Good Clinical Practice 
guidelines, including a standardized Progress Note entry format that prompts advancing of 
certain event types to the PI for consideration and maintenance of an Events Log for 
documenting decisions, outcomes, and annual IRB reporting.