A Double-Blind Placebo-Controlled Multi-Site Randomized Cross-Over Study of the Effectiveness and Efficacy of the PowerSleep Device
Phase: NA
Conditions: Sleep Deprivation, Insufficient Sleep Syndrome, Healthy
Sponsor: Philips Respironics

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 1 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 
 
A Double-Blind Placebo-Controlled Multi-Site Randomized Cross-Over Study of 
the Effectiveness and Efficacy of the PowerSleep device 
 
 
 
 
 
 
Clinical Protocol  
 
Protocol # AI-16128-PSPIV-LO 
 
Ver : 2.0 
September 18, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sponsored by 
 
 
 
Respironics, Inc., a Philips company ("Philips Respironics")  
1740 Golden Mile Highway 
Monroeville, PA 15146 
USA 
 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 2 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
Table of Contents 
DOCUMENT CONTROL PAGE................................................................................................... 3 
PROTOCOL APPROVALS ........................................................................................................... 4 
PROTOCOL REVISIONS ............................................................................................................. 5 
RESPIRONICS, INC.  CONTACT INFORMATION ................................................................... 6 
GLOSSARY ................................................................................................................................... 7 
I.  BACKGROUND AND SIGNIFICANCE.................................................................................. 9 
II. SPECIFIC AIMS/HYPOTHESIS ............................................................................................ 11 
III. STUDY DESIGN and METHODS ........................................................................................ 11 
A. Design: .............................................................................................................................. 11 
B. 
Study Participants ............................................................................................................. 11 
Inclusion Criteria .................................................................................................................. 12 
Exclusion Criteria ................................................................................................................. 12 
C. 
Study Procedures and Measurements ............................................................................... 15 
D. Temporary Discontinuation Criteria ................................................................................. 19 
E. 
Outcome Measurements.................................................................................................... 20 
F. 
Other Measurements ......................................................................................................... 22 
IV. ADVERSE EVENTS.............................................................................................................. 22 
V. STATISTICAL ANALYSIS.................................................................................................... 23 
Determination of Sample Size .................................................................................................. 24 
General Considerations ............................................................................................................. 24 
Subject Disposition ................................................................................................................... 24 
Demographics and Baseline Characteristics ............................................................................. 24 
Treatment Compliance .............................................................................................................. 24 
Primary Efficacy Analysis ........................................................................................................ 24 
Secondary Efficacy Analysis .................................................................................................... 25 
Safety Analysis ......................................................................................................................... 25 
Interim Analysis ........................................................................................................................ 25 
VI. PROTECTION FOR HUMAN PARTICIPANTS ................................................................. 25 
VII. MONITORING AND QUALITY ASSURANCE ................................................................ 27 
VIII. Registration on ClinicalTrials.gov ....................................................................................... 27 
IX. REFERENCES ....................................................................................................................... 28 
APPENDIX I ................................................................................................................................ 32 
APPENDIX II ............................................................................................................................... 33 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 3 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
DOCUMENT CONTROL PAGE 
 
Protocol Title:   
A Double-Blind Placebo-Controlled Multi-Site Randomized 
Cross-Over Study of the Effectiveness and Efficacy of the 
PowerSleep Device  
 
Protocol Number:  
#  AI-16128-PSPIV-LO 
 
 
Protocol Version:  
2.0 
 
Version Date:  
 
September 18, 2017 
 
 
Author(s): 
  
David White M.D., Anandi Mahadevan, Gary Lotz, Lynn 
Ostrowski, Barbara Miller, Noah Papas, Jeff Jasko 
 
 
 
Study Monitor(s) 
Lynn Ostrowski 
Clinical Project Manager 
Phone: (724) 387-7944 
Cell: (412) 719-1245 
E-mail: lynn.ostrowski@philips.com 
 
Barbara Miller 
Clinical Research Professional 
Phone: (724) 387-4414 
Cell: (724) 708-7048 
E-mail: barbara.miller_1@philips.com 
 
Noah Papas  
Clinical Project Manager 
Phone:  724-387-4565 
Cell: 412-277-6436 
noah.papas@philips.com 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 4 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
PROTOCOL APPROVALS 
 
Protocol Title: A Double-Blind Placebo-Controlled Multi-Site Randomized Cross-Over 
Study of the Effectiveness and Efficacy of the PowerSleep Device  
Protocol Number: # AI-16128-PSPIV-LO 
Protocol Version/Date: 2.0, September, 2017 
 
Investigator Agreement. 
As Investigator of the study entitled “A Double-Blind Placebo-Controlled Multi-Site 
Randomized Cross-Over Study of the Effectiveness and Efficacy of the PowerSleep 
Device” , Protocol # AI-16128-PSPIV-LO, I agree to:  
 
(i) conduct the Study in accordance with: this Investigator Agreement; the Study’s 
Protocol as approved by the IRB (the “Protocol”); all applicable laws and regulations; 
Good Clinical Practice and the Declration of Helsinki; and any IRB or FDA conditions of 
approval;   
 
(ii) await IRB approval for the Protocol before obtaining informed consents; 
 
(iii) ensure that all requirements for informed consent are met and not let any subject 
participate in the Study before obtaining that subject’s informed consent;  
 
(iv) not make modifications to the Protocol as supplied to me by Respironics, Inc. (the 
“Sponsor”), without first obtaining the written approval of the Sponsor;  
 
(v) provide the Sponsor with accurate financial information as required by FDA 
regulations; 
 
(vi) supervise all testing of investigational devices that involves any Study subject;  
 
(vii) maintain Study documentation for the period of time as required by FDA regulations;  
 
(viii) will supply to the Sponsor, as part of this Investigator Agreement, my curriculum 
vitae. 
 
 
 
 
 
 
Investigator Signature: 
 
 
 
 
Date:  
 
 
 
Printed Name: 
 
 
 
 
 
 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 5 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
PROTOCOL REVISIONS 
 
Revision 
Level 
 
Changes Made to Protocol 
 
Date 
 
By 
0.0 
Original Release 
02/28/2017 
L. Ostrowski, D. 
White, A. 
Mahadevan, B. 
Miller, N. Papas, G. 
Lotz, J. Jasko 
1.0 
Amendment 1: Update to aims, 
statistical section, study 
procedures, and inclusion of 
international study interim analysis 
03/16/2017 
B. Miller, L. 
Ostrowski, N. Papas 
J. Jasko  
2.0 
Amendment 2:  Increase study 
enrollment 
9/18/17 
B. Miller, L. 
Ostrowski 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 6 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
RESPIRONICS, INC.  CONTACT INFORMATION 
 
 
Technical Assistance 
The following Philips Respironics employees are available for consultation, assistance, 
and/or problem solving during the course of this research study: 
 
Anandi Mahadevan 
Senior Engineer 
Phone: (330) 835-7089 
Email: anandi.mahadevan@philips.com  
 
Reporting of Adverse Events or Adverse Device Effects 
Report the occurrence of an adverse event or adverse device effect to Philips 
Respironics within 24 hours of the occurrence. 
 
Lynn Ostrowski 
Clinical Project Manager 
Phone: (724) 387-7944 
Cell: (412) 719-1245 
E-mail: lynn.ostrowski@philips.com 
 
Or  
 
Gary Lotz 
Director, Clinical Research 
Phone: (724)733-5812 
E-mail: gary.lotz@philips.com 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 7 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
GLOSSARY 
 
Actigraph: A wrist-watch-like device placed on the wrist to measure motor activity.  The 
device continually records movements and ambient light intensity.  Collected data are 
downloaded to a computer and analyzed offline.  Analysis of activity/ inactivity can be 
further analyzed to estimate sleep patterns. 
 
Apnea: The cessation of airflow at the nostrils and mouth for at least 10 seconds as 
determined using nasal-oral thermistor, nasal pressure or device flow 
 
Apnea/Hypopnea Index (AHI): The number of apneas and hypopneas per hour of 
sleep. 
 
Hypopnea: Shallow breathing in which the air flow in and out of the airway is 
significantly reduced as detected by nasal pressure or device flow - often associated 
with oxygen desaturation of 4% or EEG arousal. 
 
Obstructive Sleep Apnea (OSA): a disorder in which the airway collapses, either 
completely or partially, repeatedly during the night and is associated with desaturation, 
sleep fragmentation, and daytime sleepiness.  
 
Polysomnography (PSG):  Continuous and simultaneous recording of physiological 
variables during sleep, including EEG, EOG (the basic stage scoring signals). EEG 
(FPz-M1, F3-M2, F4-M1, C3-M2, C4-M1, O1-M2, O2-M1), EOG (E1-M2, E2-M2).  
  
PowerSleep device: A wearable and non-invasive device, consisting of a silicone 
headband with 1 integrated electrode and headphones covered by speaker foam over 
each ear.  The headband is connected via a tether cable to a user interface which 
houses the electronics of the device.  The headband is adjustable via a Velcro strap.  
The device also includes a right mastoid electrode. EEG can be monitored and 
recorded by the PowerSleep device.  Soft audio tones (below 65dB) can be 
administered via the speakers during deep sleep throughout the night.   
 
Sleep deprivation: is defined by insufficient sleep to support adequate alertness, 
performance and health, either because of reduced total sleep time or fragmentation of 
sleep by brief arousals. 
 
Sleep restriction: is also known as chronic sleep deprivation, and exists when the 
individual routinely sleeps less than required for optimal functioning.  
 
Slow Wave Activity:   is slow high-amplitude EEG oscillations which occur during Slow 
Wave Sleep.  
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 8 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
Slow Wave Sleep (SWS):  is the deepest stage of non-rapid eye movement (nREM) 
sleep.  It is one of the two core sleep stages in mammals.  SWS alternates with rapid-
eye-movement (REM) sleep in a cyclical pattern.  SWS is predominant during the early 
part of sleep and decreases in intensity and duration across the sleep period.  SWS is 
known as deep sleep. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 9 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
I.  BACKGROUND AND SIGNIFICANCE 
Sleep is increasingly recognized as important to public health.  Sleep insufficiency may 
be defined as a condition where sleep duration or/and sleep quality is insufficient to 
support adequate alertness, performance, and health [1].  Sleep insufficiency has been 
linked to motor vehicle crashes, industrial disasters, medical and other occupational 
errors, reduced quality of life and productivity and a higher risk of chronic diseases such 
as hypertension, diabetes, depression, and obesity, and cancer [2]. Sleep insufficiency 
may be caused by behavioral sleep restriction to meet the demands and opportunities 
of modern society, but may reflect non-restorative sleep due to shallow and/or 
fragmented sleep [2].  The Center for Disease Control examined the prevalence of 
“insufficient sleep or rest during the past month” among American adults [3].  After 
adjustment for age, the prevalence of “insufficient sleep or rest” ranged from 7.9% to 
19.3% [4].   In 2009, an average of 35% of Americans within the age range of 35-<45yrs 
reported falling asleep unintentionally during the past month [4].  
 
In individuals between the ages of 20-60 slow-wave sleep (SWS), the deepest stage of 
non-rapid-eye movement (NREM) sleep, comprises between 10 and 30% of total sleep 
time[5]. During SWS, high amplitude, low frequency oscillations, referred to as slow 
waves or delta waves, appear in the EEG [6].  Larger slow waves reflect deeper, more 
intense sleep that is less likely to be fragmented or interrupted[7].  When slow-wave 
activity (SWA) is acutely suppressed by arousal stimuli or total sleep deprivation, a 
rebound occurs during the recovery night.  
 
A large body of evidence indicates that SWA is a pivotal component of the restorative 
effects of sleep for both the brain and the rest of the body [6, 8-24].  SWA has beneficial 
effects on memory and learning [25] as well as on hormonal function [26], glucose 
metabolism [9, 24, 27] and cardiovascular regulation [23, 28].  Experimental studies 
have shown that insufficient amounts of SWS lead to impaired alertness and cognitive 
performance [2, 29], obesity [30] and a higher risk of cardio and metabolic disease [11, 
20, 31].  Low amounts of SWS are also typical of normal aging [5, 32-36], and of 
common sleep disorders such as obstructive sleep apnea [37] and insomnia [38].   
Increasing the amount and intensity of SWS may have a wide range of beneficial effects 
on daytime function, quality of life and physical and mental health [2, 6, 33, 38-41]. 
 
Currently available sleeping medications, whether prescription or over the counter, have 
not been shown to increase SWA [42].  In fact, the most commonly used prescription 
sleep medications decrease SWA and are therefore often associated with residual 
daytime sleepiness despite increased sleep duration [43].  Nutritional supplements such 
as melatonin do not increase SWS or SWA and may decrease it [44].  Thus, there is a 
need for a new approach to increase the depth of NREM sleep. 
 
Researchers at the University of Wisconsin have found that the timed delivery of 
auditory stimuli during sleep that are not consciously perceived can enhance SWA 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 10 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
throughout the night [6, 41]. The findings have led to the development of several 
prototype devices which have demonstrated increasingly higher performance.  The goal 
of the present study is to test the most recent prototype, named PowerSleep, in active 
adults who have insufficient sleep. 
 
PowerSleep is a non-invasive portable light weight device designed to stimulate slow-
wave sleep and thereby reduce daytime sleepiness associated with insufficient sleep or 
poorly perceived sleep quality [45].  Auditory stimulation is provided during SWS, to 
compensate for insufficient sleep duration by increasing sleep intensity or to improve 
sleep quality by increasing sleep intensity.  Sleep intensity can be objectively assessed 
by Slow-Wave Activity (SWA), defined as EEG spectral power in the frequency range 
0.75-4 Hz.  In normal individuals, a reduction in the amount of SWA consistently results 
in reduced alertness with impaired performance due to cognitive and memory deficits 
[41].   
 
The PowerSleep device delivers acoustic stimuli that are calibrated to stimulate SWA 
without awakening the user.  The PowerSleep device is wearable and non-invasive, 
consisting of a silicone headband with integrated electrodes and speakers over each 
ear.  The headband is connected via a tether cable to a user interface which houses the 
EEG amplifier and electronics of the device.   The headband is adjustable via a Velcro 
strap.  The device also includes a right mastoid electrode.  The device monitors and 
records EEG throughout the night, and is capable of on-line identification of sleep 
stages and continuous EEG analysis.  The user interface contains the device 
electronics.   EEG data collected by the PowerSleep device can be transferred to the 
computer by a technician after home use and used to assess sleep quality.  Soft audio 
tones (below 65dB to prevent arousals from sleep) will be administered via the speakers 
during deep sleep throughout the night.    
 
A pilot study with 27 participants (average age 36.7 + 7.3, 16 female/9 male), was 
conducted by Philips Respironics. The study showed that it is possible to enhance slow 
wave sleep by using non-pharmacological methods such as auditory stimulation (AS) 
and that coupled with closed-loop brain activity monitoring (EEG) provided by the device 
provides an increase in slow wave activity by 7% which helps improve vigilance, 
cognitive functions, and memory, as well as subjective ratings of sleepiness, physical 
fatigue, and mental tiredness1. 
 
In addition, interim results (N=9) from an in-lab study conducted with the PowerSleep 
device, 77.8 % showed an increase in SWA ranging from 5-33%.  Participants showed 
an improvement in cognitive outcomes following acoustic stimulation during overnight 
sleep.  Improvements were noted in executive function task (verbal fluency), vigilance 
                                                 
 
1 Internal Philips Respironics Report- data on file 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 11 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
and alertness (PVT) and sleep dependent declarative memory task (Paired associates 
memory task).2 
 
 
II. SPECIFIC AIMS/HYPOTHESIS 
 
Primary Aim(s): 
To assess the effects of the auditory stimulation delivered by the PowerSleep 
device in adults who are sleep restricted. Efficacy will be evaluated based on the 
average of two nights (2 night) use of active PowerSleep (delivering audio tones) 
compared to the average of two nights (2 nights) use of a sham device (delivering 
no audio tones).   
 
 
It is hypothesized that the use of active PowerSleep, as compared to the sham device, 
will result in a significant increase (≥5%), in mean total slow-wave activity (SWA) over 
the 2 work nights of use. 
 
Secondary Aims: 
To evaluate the effect of 2 nights of PowerSleep use on MSLT (sleep latency), 
subjective sleepiness scales, and cognitive testing.  
 
To evaluate the relationship between MSLT (sleep latency), subjective sleepiness 
scales, and cognitive testing changes and changes in SWA.  
 
III. STUDY DESIGN and METHODS 
A. Design: 
This study is a randomized, double-blind, placebo-controlled  cross-over study designed 
to evaluate the effectiveness and efficacy of 2 consecutive  work days of nightly use of 
active versus sham PowerSleep devices in adults with self-imposed restricted sleep 
schedules.  The primary analysis will be intent-to-treat with the secondary analysis as 
an as-treated analysis.  The expected duration of the study for each participant is up to 
4 weeks. 
 
B. Study Participants:   
It is anticipated that the study will screen 100 individuals in order to complete a total of 
up to 75 participants.  We will recruit male and female participants who satisfy the 
inclusion and exclusion criteria outlined in the following sections.   
 
Potential participants will be recruited predominantly through media advertisements (ex. 
local newspapers, flyers), institutional postings, market research firms, word of mouth, 
                                                 
 
2 Internal Philips Interim Report- Data on File 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 12 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
or existing site databases of individuals who may have previously indicated an interest 
in participating in research. 
 
Inclusion Criteria 
 Able to provide written informed consent prior to admission  
 Able to read, write and speak English  
 Adult volunteers aged 21-50 years  
 Working full time with a regular work schedule; Full time is considered 4- 10 
hour days or 5- 8 hour days with a start time of 7am or later 
 Self-reported regular sleep schedule who are able to maintain their sleep 
schedule during the course of the study  
 Self-reported sleep duration of > 5hrs. and ≤ 7 hrs. +/- 15 minutes (verified by 6 
work days of ambulatory sleep monitoring with wrist actigraphy and daily logs) 
 Self-reported sleep latency > 30 minutes no more than once / wk. (time to fall 
asleep) 
 Self-reported wake time after sleep onset ≤ 30 minutes 
 Participants who regularly use an alarm clock during the work week and who 
self-report: 
i. 
Regular time in bed (TIB) on work days of ≤7 hours  
ii. 
Regular increase in sleep duration by ≥ 1 hour during non-work days as 
compared to work days, either by nocturnal bedtime extension of via a 
daytime nap 
 
Exclusion Criteria:  
 Participation in another interventional study in the past 30 days. 
 Previously enrolled in a PowerSleep study.  
 Major controlled* or uncontrolled medical condition such as congestive heart 
failure, neuromuscular disease, renal failure, cancer, COPD, respiratory failure or 
insufficiency, or patients requiring oxygen therapy (as determined by self-report 
and reviewed by the study PI.) 
 Currently working night, swing, split or rotating shift. 
 Current use or use of within the past month of a prescription or over-the-counter 
sleep medication or stimulant; use of psychoactive medication (based on self-
report and review with a study clinician).  Refer to table below for examples.  
 Pregnant or currently breast feeding 
 Current Smokers or using nicotine replacement therapy.  Those that have been 
nicotine free for 30 days will be included. 
 Body Mass Index > 40 kg/m2    
 Prior diagnosis of any sleep disorder including 
a. Obstructive Sleep Apnea (AHI ≥15 events/hour) – from ambulatory or in 
lab polysomnography 
b. Restless legs syndrome, or periodic limb movement disorder  

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 13 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
c. Insomnia 
d. Parasomnia 
 High Risk of OSA based on STOP-BANG Questionnaire (“yes” on at least 4 of 8 
questions) 
 High Risk of Restless Legs Syndrome (RLS) based on Cambridge-Hopkins 
Screening questionnaire 
 High Risk of Insomnia based on Insomnia Severity Index (score of 22 or higher) 
 Self-reported history of excessive alcohol intake- self-report > 21 drinks / wk or 
binge alcohol consumption ( >5 drinks per day)  
 Excessive caffeine consumption (> 650mg/day combining all caffeinated drinks 
regularly absorbed during workdays.)  Caffeine intake must be regular and 
maintained throughout study and on testing days  
 Individuals who self-report a history of recurrent seizures or epilepsy or have a 
history of medical conditions that could increase the chance of seizures (e.g. 
stroke, aneurysm, brain surgery, structural brain lesion). 
 Individuals who self-report severe contact dermatitis or allergy to silicone, nickel 
or silver. 
 Individuals who self-report moderate hearing loss. 
 Inability to achieve appropriate headband fit. 
 Planned travel across more than one time zone one month prior to and or during 
the anticipated period of the study with PowerSleep device use  
 Intentional naps during the work week. 
 Alpha-Delta waveforms as determined by Baseline night PowerSleep Device 
data collection 
 
*Participants who are on a stable and well-tolerated pharmacological treatment for 
hypertension, dyslipidemia, or thyroid replacement will not be excluded as long as they 
continue to take their medication at the same dose and at the same time(s) of day.    
 
Concomitant Medications: 
   
The Investigator will make all final decisions regarding exclusion of participants on the 
basis of medication. 
 
Classes of medications that will not be allowed include: 
Class 
Examples 
Sedating Antihistamines 
chlorpheniramine, brompheniramine, 
diphenhydramine, doxylamine 
OTC Decongestants 
phenylephrine, ephedrine, 
pseudoephedrine 
Sedative/Hypnotics 
zolpidem, eszopiclone, zaleplon, 
ramelteon, triazolam, gabitril, tiagabine, 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 14 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
suvorexant, gamma-hydroxybutyrate, 
tasimelteon 
Anxiolytics 
alprazolam, clonazepam, diazepam, 
lorazepam 
Sedating Antidepressants 
amitriptyline, nortriptyline,  duloxetine, 
venlafaxine, mirtazapine, nefazodone, 
buspirone,  
Medications for Attention Deficit 
Hyperactivity Disorder 
atomoxetine, methylphenidate, 
amphetamine 
Stimulants 
amphetamine, modafinil, armodafinil 
Dopamine Agonists 
ropinirole, pramipexole, rotigotine 
Narcotic/Opioid Analgesics 
Including tramadol 
Dextromethorphan 
Many OTC cough products 
Dietary supplements and other 
preparations affecting sleep-wake 
regulation 
Kava (Piper methysticum), Ashwagandha 
(Withania somnifera), Valerian (Valeriana 
officinalis), St. Johns Wort (Hypericum 
Perforatum) 
OTC stimulants 
Diet aids 
Melatonin 
 
Psychoactive medications, medications associated with drowsiness/sedation and 
stimulants will not be allowed because they could interfere with study outcomes.  These 
include prescription, over-the-counter and dietary/herbal supplements.  The use of such 
medications must be discontinued for 2 weeks prior to Visit 1.  Participants who develop 
a cold or flu during the work week use of the device should contact the study team 
immediately to discuss medication usage. The Investigator will make all final decisions 
regarding exclusion of participants on the basis of medication. 
 
Before enrolling a woman of child-bearing potential in this clinical study, Investigators 
must review the following information with the participant: 
• Risk of pregnancy; 
• Contraceptives in current use; 
• Drug interactions with hormonal contraceptives; and 
• Pregnancy prevention during the study. 
 
All women of child bearing potential, (defined as any woman, unless surgically sterile or 
postmenopausal for at least 1 year) must be instructed to contact the Investigator 
immediately if they suspect they might be pregnant while participating in this study. If a 
participant becomes pregnant, she will be discontinued from the study 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 15 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
C. Study Procedures and Measurements:  
Participants may be pre-screened over the phone by the site or a market research firm 
to determine eligibility.  A screening script will include a general review of key inclusion 
and exclusion criteria, the STOP-BANG questionnaire to assess the risk / possibility of 
an undiagnosed sleep disorder [46] and other questionnaires.  Participants that meet all 
eligibility criteria will be asked to come into the office for a screening daytime visit (Visit 
1) involving a detailed presentation of the study (informed consent) and an interview to 
verify eligibility and work schedules.   
 
Participants who are interested and eligible will be consented.  Participants will 
scheduled for a second daytime visit, 5 overnight lab visits, and provided with 
information on use of the actigraph.  At Daytime Visit 2, participant qualification will be 
assessed based on the PowerSleep device data, actigraphy, and sleep logs.  Qualifying 
participants will be randomized and scheduled for their sleep lab visits.   
 
Participants will use the PowerSleep device within the active and sham study arm for 
two nights each week.  After completing a baseline night in the lab, participants will 
sleep in the sleep lab two consecutive nights for two consecutive weeks.  The first week 
participants will be randomized to active or sham and complete two consecutive nights.  
Participants will be asked to come in the same nights the following week to cross-over 
to the other arm of the study. 
 
Daytime Visit 1 Procedures (Up to 2 hours): 
Initial evaluation and anthropometric measurements: 
Participants will be asked to report to the office for a daytime visit.  After a full 
explanation of the consent and after all the participants’ questions have been answered, 
they will be asked to sign the consent form.  A detailed interview will be performed 
verifying eligibility criteria, and review of work and non-work schedules.   
 
Participants will be asked to fill out the following baseline questionnaires:  
 Medical History Questionnaire and Review of Systems 
 Epworth Sleepiness Scale  
 Insomnia Severity Questionnaire 
 Cambridge-Hopkins Questionnaire (RLS screening) 
 STOP-BANG Questionnaire 
 Questions about sleep schedule and sleep quality. 
 
Participants will have their height, weight, neck circumference, temperature, respiratory 
rate and blood pressure including heart rate (heart rate, systolic and diastolic after being 
seated for approximately 5 minutes) recorded.  
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 16 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
Participants will be trained on the use of the sleep logs and actigraphy including 
instructions from the study staff on how to wear the actigraph.  Participants will be 
asked to keep a sleep log and wear an actigraph during the entire course of the study.   
It is important participants keep to their regular sleep schedule throughout the study. 
 
Baseline Night (Sleep-Lab night 1):  
Participants will be asked to come into the sleep-lab for a baseline night.  This visit 
should occur as close as possible to Daytime Visit 2, preferably the night before the 
visit.  If this cannot occur at that date due to the sleep lab or participant schedule this 
visit should be conducted at least 6 work days after the participant starts wearing the 
actigraph.  Participants will be asked to come into the lab up to 4 hours before bedtime.  
Participants will be fitted with the PowerSleep device and PSG electrodes and asked to 
go to bed and awaken at the same time as their regular work-night sleep schedule.  
Participants will then be able to leave to complete their day.  See Appendix I for 
standardized rules and restrictions for participant activities for the in lab study. 
 
Daytime Visit 2 Procedures (2 hours): 
Participants will return to the office (within 2 weeks of daytime visit 1, ±2 days) with the 
actigraph and sleep diary for review by the study staff.  Those participants who 
demonstrated alpha-delta waveforms as detected by the PowerSleep device during the 
baseline night will be excluded. 
 
Actigraphy review: 
The sleep log and actigraph data will be reviewed by trained study staff prior to 
randomization to ensure participants continued eligibility.  
 
Eligible participants will be randomly assigned to active or sham treatment during this 
visit in a 1:1 ratio.  Participants and study staff will be blinded to the treatment they are 
receiving during each work week.     
 
Active treatment: Participants will wear the PowerSleep device with soft audio 
tones (below 65dB to prevent arousals from sleep) administered via the speakers 
during deep sleep throughout the night. 
 
Sham treatment: Participants wear the same PowerSleep device as with the 
active treatment, however no audio tones will be administered via the speakers. 
 
Those participants that state they have heard tones during the baseline night will be set 
to a sensitive setting. 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 17 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
Overnight in-lab visit 2  (Work Week 1) 
Participants will be asked to come into the sleep lab during their work week on a 
Tuesday – Thursday night to complete their first study arm night.  Participants will be 
asked to report to the lab up to 4 hours before bedtime with all study materials.  Women 
of child-bearing potential will be asked to take a urine-pregnancy test. Prior to bedtime 
participants will go through a learning activity of the assessments they will complete the 
following night in order to have an understanding of the tasks.  Participants will be fitted 
with the PowerSleep device, PSG electrodes and asked to go to bed and awaken at the 
same time as their regular work-night sleep schedule.  Participants will complete the 
KSS, Samn Perelli, and VAS Sleep Quality 60 minutes of waking.   After completing the 
questionnaires participants will be able to go to work, but will be instructed to not nap 
during the day.  They will return to the sleep lab that evening 3 hours before bedtime.   
 
Overnight in-lab visit 3 (Work Week 1) followed by Daytime in-lab testing (8 
hours): On the next evening participants will be asked to return to the sleep lab for the 
second study arm night.  Participants will be asked to report to the lab up to 4 hours 
before bedtime. Participant will be asked to complete the PAL learning activity prior to 
bedtime (120 to 30 minutes before lights out).  Participants will be asked to go to bed 
and awaken at the same time as their regular work-night sleep schedule.  Participants 
will be asked to wear the PowerSleep device and PSG electrodes during this overnight 
visit. 
On the morning of the day following the overnight in lab visit work week 1, participants 
will remain in the lab and undergo the following assessments: 
 
After Wake-Up 
 Collect and download PowerSleep device data 
 
Anytime after wake-up 
 Review of any reported changes in medical condition since last visit 
 Collect sleep logs 
 Data download from actigraph  
 Questionnaire identifying whether participant believes they had undergone 
active versus sham treatment 
 Breakfast- participants can have one (1) 6 ounce cup of coffee or caffeine 
equivalent.  Coffee or equivalent is only for those who routinely drink 
caffeine in the morning. 
 Lunch 
 
1 hour after wake up: 
 Complete morning recall of PAL task 
 Complete 3 minute PVT 
 VAS for sleep quality 
 Verbal fluency 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 18 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 Karolinska Sleepiness Scale 
 Samn-Perelli Fatigue Scale 
 
2 hours after wake up: 
 
 4- Research Multiple Sleep Latency Test (see Appendix II for standardized 
MSLT procedures) each nap is followed by the following assessments: 
o Complete a 3 minute PVT  
o VAS for mood and vigor 
o Karolinska Sleepiness Scale 
o Samn-Perelli Fatigue Scale 
 
  
 
Participants will continue to wear the actigraph and complete sleep logs until the next 
set of overnight visits. 
 
Overnight in-lab visit 4 (Work Week 2)  
Participants will be asked to come into the sleep lab during their second work week on a 
Tuesday – Thursday night to complete the cross-over week portion of the study.  
Participants will be asked to report to the lab up to 4 hours before bedtime with all study 
materials.  Women of child-bearing potential will be asked to take a urine-pregnancy 
test. Participants will be fitted with the PowerSleep device, PSG electrodes and asked 
to go to bed and awaken at the same time as their regular work-night sleep schedule.  
Participants will complete the KSS, Samn Perelli, and VAS Sleep Quality 60 minutes of 
waking.   After completing the questionnaires participants will be able to go to work, but 
will be instructed to not nap during the day.  They will return to the sleep lab that 
evening 3 hours before bedtime.   
 
 
Overnight in-lab visit 5 (Work Week 2) followed by Daytime in-lab testing (8 hours) 
On the next evening participants will be asked to return to the sleep lab for the second 
study arm night.  Participants will be asked to report to the lab up to 4 hours before 
bedtime. Participant will be asked to complete the PAL learning activity prior to bedtime 
(120 to 30 minutes before lights out).  Participants will be asked to go to bed and 
awaken at the same time as their regular work-night sleep schedule.  Participants will 
be asked to wear the PowerSleep device and PSG electrodes during this overnight visit.   
 
After Wake-Up 
 Collect and download PowerSleep device data 
 
Anytime after wake-up 
 Review of any reported changes in medical condition since last visit 
 Collect sleep logs 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 19 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 Data download from actigraph  
 Questionnaire identifying whether participant believes they had undergone 
active versus sham treatment 
 Breakfast- participants can have one (1) 6 ounce cup of coffee or caffeine 
equivalent.  Coffee or equivalent is only for those who routinely drink 
caffeine in the morning. 
 Lunch  
 
1 hour after wake up: 
 Complete morning recall of PAL task 
 Complete 3 minute PVT 
 VAS for sleep quality 
 Verbal fluency 
 Karolinska Sleepiness Scale 
 Samn-Perelli Fatigue Scale 
 
2 hours after wake up: 
 
 4- Research Multiple Sleep Latency Test (see Appendix II for standardized 
MSLT procedures) each nap is followed by the following assessments: 
o Complete a 3 minute PVT  
o VAS for mood and vigor 
o Karolinska Sleepiness Scale 
o Samn-Perelli Fatigue Scale 
 
Exit Interview 
Participants may be asked to complete an exit interview.  During the interview, the 
participant will be asked to answer a set of questions about their opinions related to 
future iterations of the device, device functions, and technology preferences.  This 
interview will be conducted by a member of the study staff or study sponsor.  The 
interview may occur at the end of the study or as a phone interview.  The interview will 
require up to an hour of the participant’s time.  Participants will be asked to indicate their 
approval to have the interview audio recorded and the potential to be contacted for 
future discussions.      
 
D. Temporary Discontinuation Criteria 
If a participant develops a cold, flu or upper respiratory infection during the course of the 
work week, they may be asked to temporarily discontinue the study for one week.  
Participants will be instructed as part of the Informed Consent to call the study team if 
they develop a cold, flu or upper respiratory infection.  The study team will let the 
participant know whether or not they can temporarily exit the study and restart at a later 
date or if they will need will need to discontinue the study. 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 20 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
E. Outcome Measurements 
Performance of PowerSleep device components: 
 EEG signal quality as measured by impedance and ability to detect sleep-specific 
activity and/or events. 
 Sleep staging algorithm performance as measured by sensitivity and specificity, 
PPV compared to the gold standard scoring. 
 Audio stimulation algorithm performance as measured by the number and timing 
of tones provided. 
 
 
Slow Wave Activity: EEG as recorded by the PowerSleep device and overnight PSGs 
will be analyzed for slow wave activity.   
 
Sleep Quality: EEG from device downloads will be scored by an experienced 
registered polysomnographic technologist following current guidelines to determine 
sleep stage distribution.  Sleep quality will also be measured via the Samn-Perelli 
Fatigue Checklist, the Karolinska Sleepiness Scale (KSS), and the visual analog scales.  
 
Psychomotor Vigilance Testing – Brief (PVT – B):  The Psychomotor Vigilance Task 
is a sustained-attention, reaction-time task that measures the speed with which 
participants respond to a visual stimulus.  Sleep loss induces reliable changes in PVT 
performance, causing an overall slowing of response times, a steady increase in the 
number of errors of omission (i.e., lapses of attention, usually defined as response times 
≥ 500 ms), and a more modest increase in the number of errors of commission (i.e., 
responses without a stimulus, or false starts) [47, 48]. Typically the PVT is a 10 minute 
assessment but a shorter 3 minute version (PVT-B) has recently been validated in 
controlled laboratory studies on total and partial sleep deprivation [47].  The PVT results 
will be assessed for average reaction time, average speed, number of omission errors, 
number of commission errors, and total number of errors.  
 
Verbal Fluency:  Participants are required to generate as many words directly related 
to the instructions as they can.  This task has three conditions, the letter fluency 
condition (that has 3 trials), the category fluency condition and the switching condition. 
For each trial within each condition, the trial lasts for 60 seconds. This task is expected 
to take 6 minutes and will be audio recorded for scoring purposes. 
 
Paired associates learning task (PAL):  The Paired Associates Learning Task is a 
well-established cognitive task used to assess declarative memory.  Participants are 
presented with word pairs to learn.  Immediately following and again in the morning after 
they wake up they are tested on the recall of the words.  The recall testing involves 
showing participants one word and they are asked to state the paired word that they 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 21 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
learned previously.   Overnight memory retention is determined by the difference in the 
number of recalled words between morning retrieval testing after sleep and immediate 
recall performance at learning before sleep.  The testing is scored by a technician and 
may also be recorded for scoring confirmation.   
 
Karolinska Sleepiness Scale: The Karolinska Sleepiness Scale (KSS) measures 
subjective levels of fatigue. KSS queries subjects as to how sleepy they feel at that 
moment. The subjects answer is based on a 9-point scale where 1 = extremely awake 
and 9 = extremely sleepy/fighting to stay wake. The KSS will be administered.[49, 50]  
 
Samn-Perelli 7-pt scale: The Samn-Perelli is a 7 point scale which measures 
subjective levels of alertness.  This scale ranges from fully alert, wide awake to 
completed exhausted, unable to function effectively. [51] 
 
Visual analog scales for mood & vigor:  Subjective alertness will be assessed using 
the Visual Analog Scale for Global Vigor and Mood, which combines the scores on four 
10-cm scales (alert, sleepy, weary, and effort) to obtain a Global Vigor score between 0 
and 40 cm and the scores on four 10-cm scales (happy, sad, calm, tense) to obtain a 
Global Mood score between 0 and 40 cm.  Data are then divided by 4 to obtain a rating 
between 0-10. [52] 
 
Visual analog scale for sleep quality: Sleep quality will be assess using the Visual 
Analog Scale for Sleep Quality, which combines the scores on four 10-cm scales 
(refreshed, alert, sleep quality, and deep sleep) to obtain a Global Sleep Quality score 
between 0 and 40 cm.  Data are then divided by 4 to obtain a rating between 0-10. [53] 
 
Multiple Sleep Latency Test (MSLT)   
The MSLT is the gold standard to evaluate physiological sleepiness and consists of a 
series of five nap opportunities presented at 2-h intervals beginning approximately 2 
hours after initial (morning) awakening.  We will use a modified version of the test, with 
four instead of five naps. [54, 55] The MSLT will be scored by an experienced registered 
polysomnographic technologist following the study protocol design.  
 
 
Polysomnography:  Both the active and sham PowerSleep devices perform online 
polysomnography.  For each night of each treatment period, the recordings will be 
visually scored in 30-second epochs as wake, rapid eye movement (REM) sleep, or 
non-REM sleep stages N1, N2, and N3 according to standardized criteria. The following 
summary variables will be calculated: sleep period time (i.e. time interval separating 
sleep onset from morning awakening), total sleep time (i.e. SP – duration of intrasleep 
wake periods), sleep efficiency (i.e. total sleep time / time in bed *100), duration of REM 
sleep, duration of light non-REM sleep (i.e. stages N1+N2), and duration of deep non-
REM sleep (i.e. stage N3).  

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 22 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 
F. Other Measurements 
 
STOP-BANG Questionnaire 
This is an 8 item questionnaire which determines the risk for sleep apnea.  These are a 
series of yes no questions.  [46] 
 
Cambridge-Hopkins Screening questionnaire (for RLS) 
This is a 2 to 13 question questionnaire.  If participants answer yes to one or both of the 
first two questions then they answer a series of questions about sensations in their 
lower body.  Depending on the responses participants may be found to be ineligible to 
continue. 
 
Epworth Sleepiness Scale (ESS) 
This is an 8 item questionnaire that measures the general level of daytime sleepiness.  
Participants will be asked what the chance is they would doze off or fall asleep during 
different routine daytime situations.[56] 
 
Insomnia Severity Questionnaire 
The Insomnia Severity Index has seven questions about sleep problems. The answers 
are scored 0 to 4 and added to obtain a total score which indicates the clinical 
significance of the insomnia complaint. Total score can range from 0 (no clinically 
significant) to 28 (clinical insomnia, severe). [57] 
 
IV. ADVERSE EVENTS 
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease 
temporally associated with the use of study device, whether or not considered related to 
study device.  
 
AEs will include:  
- 
Changes in the general condition of the participant  
- 
Subjective symptoms offered by or elicited from the participant;  
- 
Signs observed by the investigator or study personnel;  
 
All concurrent disease including any change in severity or frequency of pre-existing 
disease. 
 
A serious AE is one that:  
- 
Results in death 
- 
Is an immediate threat to life 
- 
Results in permanent disability 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 23 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 
In addition, a serious AE is one that is judged by the investigator to be an important or 
medically significant event. Causality assessments of AEs: For all AEs, the investigator 
will provide an assessment of causal relationship to study device. Appropriate forms will 
be used for this purpose and filed in the case report forms and submitted to the IRB for 
review. They will be classified as related, possibly related, and not related. The severity 
will be adjudged as being mild, moderate, or severe. 
 
Adverse Event Follow-up 
Participants with non-serious adverse events that are ongoing at the participant’s last 
study visit must be followed until resolution or for 30 days after the participant’s last 
study visit, whichever comes first. Non-serious adverse events that are reported during 
the 7 days following the participant’s last study visit need to be recorded on the Adverse 
Events Case Report Form provided by the Sponsor and followed until resolution or for 
up to the 30 days after the participant’s last study visit, whichever comes first. Serious 
adverse events will be followed until the event resolves or the event or sequelae 
stabilize. Serious adverse events that are reported within 30 days of the participant’s 
last study visit should be reported on the Adverse Events Case Report Form provided 
by the Sponsor. 
 
Adverse Event Reporting Period 
Adverse events, both serious and non-serious, are to be recorded on the Adverse 
Events Case Report Form provided by the Sponsor from the time of the participant's 
informed consent signature until the end of the participant’s study participation. If the 
participant reports or the Investigator learns of a new AE(s) up to 7 days after the 
participant's last study visit or a new SAE(s) up to 30 days after the participant’s last 
study visit, the event needs to be recorded on the form provided by the Sponsor.  All 
SAEs should be reported to the Sponsor within 24 hours of occurrence. 
All device deficiencies, use or user errors, and equipment failures will be documented.  
Use or User errors will be captured as part of the source documentation.  Device 
deficiencies and equipment failures will be kept on a separate log.  The serial numbers 
and type of deficiency/failure will be captured.  Philips Respironics Engineering team will 
be notified to troubleshoot any issues associated with the PowerSleep Device. 
 
 
V. STATISTICAL ANALYSIS 
 
Data quality will be assessed by the blinded personnel scoring the PSGs and device 
data.  Criteria will be defined regarding whether the data sets are scorable and of 
sufficient duration to be included in the statistical analysis. These criteria will be 
consistently applied across all participant records and described in any study 
publications or reports. 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 24 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
Determination of Sample Size 
100 participants may be screened, up to 75 participants will be enrolled (randomized) in 
order to ensure at least 50 complete data sets. An interim analysis (N=9) from an 
international study of similar design suggests that between 24-47 participants would be 
required to reach statistical significance for the primary endpoint of slow-wave activity 
(SWA). 
 
General Considerations 
The primary analysis will include all completed participants who contributed at least one 
night of usable PSG data for each therapy condition.  If there are participants whose 
therapy order is switched from their randomized assignment, then the results will be 
analyzed according to both the as-randomized and the as-treated assignments.  If the 
sleep data are not usable for both nights in a given therapy,  those participants will be 
excluded from the primary analysis, and site(s) may over-enroll to compensate for these 
missing data.  The safety analysis will include all randomized subjects. 
 
All variables will be summarized by descriptive statistics. The statistics for continuous 
variables include mean, median, standard deviation, minimum, maximum, 95% 
confidence interval (CI) for the mean, and number of observations. For categorical 
variables, frequencies and percentages will be presented. All analyses will be 
conducted using either SAS® or SPSS® software. 
 
Subject Disposition 
Subject disposition, including the total number of participant’s enrolled, randomized, 
completed, early terminations and withdrawals, will be presented. In addition, a listing 
will be provided with the reasons for discontinuation. 
 
Demographics and Baseline Characteristics  
Standard subject demographics (e.g., age and gender) and baseline characteristics will 
be summarized for all participants enrolled and for evaluable subjects. 
Treatment Compliance 
It is expected that the drop-out rate will be low as the study is of short duration and will 
be completed in a controlled, in-lab setting.  Any discontinued participants or protocol 
deviations will be documented.  
 
 Primary Efficacy Analysis   
The primary efficacy measure for this study will be the cumulative or average slow-wave 
activity (SWA), which will be measured at multiple EEG electrode locations (channels).  
As stated in the study procedures, two PSG nights will be collected for each therapy.  

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 25 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
The primary SWA endpoint will be the average of the two nights, but secondary 
analyses will include separate assessments of the first and second nights within each 
therapy.  The data will be evaluated to determine whether they meet the assumptions of 
parametric methods.  SWA will be compared between the Active and Sham conditions, 
using either a paired t-test or the nonparametric Wilcoxon Signed Ranks test, 
depending on the distribution of the paired differences.  The comparisons will be 
performed within and between EEG channels.  The significance level will be a two-sided 
alpha of 0.05, and if necessary, this will be adjusted for multiple comparisons. 
 
Secondary Efficacy Analysis 
The daytime outcomes will be analyzed using the same statistical model as the SWA 
data.  
 
Safety Analysis 
Safety evaluations will be performed by recording clinical adverse events at the time 
originally reported and at each visit thereafter.  Adverse events will be provided in data 
listings. 
A complete medical history will be obtained at screening, and subjects having any of the 
outlined exclusion criteria will be immediately discontinued. 
 
Interim Analysis 
An interim analysis is planned when approximately 50% of the enrolled population 
completes the study.  If the effect size observed at the interim is less than originally 
expected, the sample size may be increased. 
 
VI. PROTECTION FOR HUMAN PARTICIPANTS 
 
Potential risks and discomforts:  
Overall, risks in this study are minimal. However, the potential risks are detailed below, 
and they will be described in detail in informed consent and will be repeated verbally to 
the participants prior to the studies. 
 
The application of electrodes from the PowerSleep device or PSG may include minor 
skin irritation and redness from abrasive scrub used to prepare the skin for the PSG 
electrodes and the tape used to attach the PSG electrodes. Therefore, you may have 
some discomfort with the application or removal of the electrodes from your scalp 
including skin abrasions, blisters, tape irritation and unpleasant odor.  Additionally, you 
may experience red/pressure marks that should dissipate within one hour. You may 
also experience some discomfort due to pressure of the headband on your ears.  If this 
is the case, the headband will be adjusted to reduce the pressure.  The headband used 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 26 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
for this study contains silicone.  Participants allergic to silicone will not be able to 
participate in this study.  None of the materials tested contain latex. 
 
The use of sensory stimuli during sleep does not pose unique risks.  However, although 
it is contrary to the intent of the current study, stimulation during sleep can result in 
fragmented sleep.  The effect may be similar to partial sleep deprivation, when 
participants are prevented from sleeping during a portion of the night.  The application 
of audio tones will be halted if the participant complains of any pain (including 
headaches), tinnitus, significant sleep disturbance, or if there are any unusual EEG 
activity noted. 
 
Participants will be informed that biocompatibility testing related to skin contact of the 
cable tether has not been completed.  Participants will be instructed to wear a shirt 
when wearing the device to minimize skin contact and any potential irritation.  
 
Potential benefits: 
There are no direct benefits to participants in this study. It is hoped that the results of 
this study will lead to new treatment strategies to improve sleep quality in sleep-
restricted patients. 
 
Confidentiality:  
Privacy rules and requirements according to governing regulations will be implemented. 
All the information collected as part of this study will be kept confidential. All information 
collected for this study will be kept in a secured area or stored in a password protected 
computer if digital. Audio recordings will be stored without identifiers and only include 
participant ID. Except when required by law, participants will not be identified by name, 
social security number, address, telephone number, or any other direct personal 
identifier in study records. For records disclosed outside the Philips Respironics, 
participants will be assigned a unique code number.  The key to the code will be kept by 
the investigators. Data will be managed by study number and analyzed anonymously. 
 
Withdrawal Criteria: 
The term “discontinuation “refers to the participant’s premature withdrawal from the 
study prior to completing all procedures.  Participants may be discontinued from the 
study for any of the following reasons: 
 
• 
If in the investigator’s judgement, continuation in the study may prove harmful to 
the participant.  Such a decision may be precipitated by adverse events, including fever, 
nausea, rash, changes in vital signs, or the development of a new medical condition.  
The investigator will be solely responsible for making medical/safety decisions regarding 
the participant’s continued participation in the study. 
• 
Noncompliance. 
• 
At the request of the participant. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 27 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
 
The study coordinator will document whether or not each participant completed the 
study.  If, for any participant, study treatment or assessments were discontinued, the 
reason will be recorded. 
 
VII. MONITORING AND QUALITY ASSURANCE  
 
This clinical study will be monitored by Philips Respironics Inc. (Sponsor) in compliance 
with the Code of Federal Regulations (CFR) for clinical research; namely, 21 CFR Parts 
50, 54, 56 and 812 and others as applicable. The purpose of such monitoring is to 
assure that the study remains in compliance with the approved protocol, investigator 
agreement and regulatory requirements, to verify the completeness and accuracy of 
study data and to resolve any issues that arise during the conduction of the study. The 
Sponsor will scheduled monitoring visits periodically as specified by the monitoring plan 
that will be conduct by trained clinical research professionals.  A unique source record 
will be created for each study participant.  This record will include documentation of the 
informed consent form review process, HIPAA competition according to site policies, 
concomitant medications and applicable medical history.  The Sponsor will have access 
to these source records.  An electronic data capture (EDC) will be used for this trial.  
Only those members of the study team that have completed training and have been 
delegated by the Principal Investigator will be able to access the EDC to enter data or 
make changes to the data.   It has been determined that this study does not require a 
Data Safety Monitoring Board (DSMB).  
 
VIII. Registration on ClinicalTrials.gov  
This study will be registered on ClinicalTrials.gov.   
 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 28 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
IX. REFERENCES 
1. 
Walsh, J.K., Clinical and socioeconomic correlates of insomnia. J Clin Psychiatry, 2004. 
65 Suppl 8: p. 13-9. 
2. 
Banks, S. and D.F. Dinges, Behavioral and physiological consequences of sleep 
restriction. J Clin Sleep Med, 2007. 3(5): p. 519-28. 
3. 
Wheaton AG, L.Y., Perry GS, Croft JB., Effect of short sleep duration on daily activities-
-United States, 2005-2008. MMWR Morb Mortal Wkly Rep, 2011. 60(8): p. 239-42. 
4. 
McKnight-Eily LR, L.Y., Wheaton AG, Croft JB, Perry GS, Okoro CA, Strine T., 
Unhealthy sleep-related behaviors--12 States, 2009. MMWR Morb Mortal Wkly Rep, 
2011. 60(8): p. 233-8. 
5. 
Ohayon, M.M., et al., Meta-analysis of quantitative sleep parameters from childhood to 
old age in healthy individuals: developing normative sleep values across the human 
lifespan. Sleep, 2004. 27(7): p. 1255-73. 
6. 
Tononi, G. and C. Cirelli, Sleep function and synaptic homeostasis. Sleep Med Rev, 
2006. 10(1): p. 49-62. 
7. 
Bonnet, M.H., L.C. Johnson, and W.B. Webb, The Reliability of Arousal Threshold 
During Sleep. Psychophysiology, 1978. 15(5): p. 412-416. 
8. 
Aeschbach, D., A.J. Cutler, and J.M. Ronda, A Role for Non-Rapid-Eye-Movement Sleep 
Homeostasis in Perceptual Learning. The Journal of Neuroscience, 2008. 28(11): p. 
2766-2772. 
9. 
Copinschi, G., R. Leproult, and K. Spiegel, The important role of sleep in metabolism. 
Front Horm Res, 2014. 42: p. 59-72. 
10. 
Diekelmann, S. and J. Born, The memory function of sleep. Nat Rev Neurosci, 2010. 
11(2): p. 114-126. 
11. 
Guyon, A., et al., Adverse effects of two nights of sleep restriction on the hypothalamic-
pituitary-adrenal axis in healthy men. J Clin Endocrinol Metab, 2014. 99(8): p. 2861-8. 
12. 
Huber, R., et al., Local sleep and learning. Nature, 2004. 430(6995): p. 78-81. 
13. 
Huber, R., et al., Arm immobilization causes cortical plastic changes and locally 
decreases sleep slow wave activity. Nat Neurosci, 2006. 9(9): p. 1169-1176. 
14. 
Landsness, E.C., et al., Sleep-dependent improvement in visuomotor learning: a causal 
role for slow waves. Sleep, 2009. 32(10): p. 1273-84. 
15. 
Marshall, L. and J. Born, The contribution of sleep to hippocampus-dependent memory 
consolidation. Trends Cogn Sci, 2007. 11(10): p. 442-50. 
16. 
Molle, M., et al., Learning increases human electroencephalographic coherence during 
subsequent slow sleep oscillations. Proc Natl Acad Sci U S A, 2004. 101(38): p. 13963-8. 
17. 
Plihal, W. and J. Born, Effects of early and late nocturnal sleep on declarative and 
procedural memory. J Cogn Neurosci, 1997. 9(4): p. 534-47. 
18. 
Rasch, B. and J. Born, About sleep's role in memory. Physiol Rev, 2013. 93(2): p. 681-
766. 
19. 
Romeijn, N., et al., Cold Hands, Warm Feet: Sleep Deprivation Disrupts 
Thermoregulation and Its Association with Vigilance. Sleep, 2012. 35(12): p. 1673-1683. 
20. 
Tasali, E., et al., Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl 
Acad Sci U S A, 2008. 105(3): p. 1044-9. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 29 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
21. 
Tononi, G. and C. Cirelli, Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull, 
2003. 62(2): p. 143-50. 
22. 
Tononi, G. and C. Cirelli, Sleep and the price of plasticity: from synaptic and cellular 
homeostasis to memory consolidation and integration. Neuron, 2014. 81(1): p. 12-34. 
23. 
Vaara, J., et al., The effect of 60-h sleep deprivation on cardiovascular regulation and 
body temperature. Eur J Appl Physiol, 2009. 105(3): p. 439-44. 
24. 
Van Cauter, E., et al., Metabolic consequences of sleep and sleep loss. Sleep Med, 2008. 
9 Suppl 1: p. S23-8. 
25. 
Tamminen, J., M.A. Lambon Ralph, and P.A. Lewis, The Role of Sleep Spindles and 
Slow-Wave Activity in Integrating New Information in Semantic Memory. The Journal of 
Neuroscience, 2013. 33(39): p. 15376-15381. 
26. 
Leproult, R. and E. Van Cauter, Role of Sleep and Sleep Loss in Hormonal Release and 
Metabolism. Endocrine development, 2010. 17: p. 11-21. 
27. 
Wisor, J.P., et al., Sleep Slow-Wave Activity Regulates Cerebral Glycolytic Metabolism. 
Cerebral Cortex (New York, NY), 2013. 23(8): p. 1978-1987. 
28. 
Burgess, H.J., A.L. Holmes, and D. Dawson, The relationship between slow-wave 
activity, body temperature, and cardiac activity during nighttime sleep. Sleep, 2001. 
24(3): p. 343-9. 
29. 
Alhola, P. and P. Polo-Kantola, Sleep deprivation: Impact on cognitive performance. 
Neuropsychiatric Disease and Treatment, 2007. 3(5): p. 553-567. 
30. 
Beccuti, G. and S. Pannain, Sleep and obesity. Current opinion in clinical nutrition and 
metabolic care, 2011. 14(4): p. 402-412. 
31. 
Knutson, K.L., Sleep duration and cardiometabolic risk: a review of the epidemiologic 
evidence. Best practice & research. Clinical endocrinology & metabolism, 2010. 24(5): p. 
731-743. 
32. 
Dijk, D.J., D.G. Beersma, and R.H. van den Hoofdakker, All night spectral analysis of 
EEG sleep in young adult and middle-aged male subjects. Neurobiol Aging, 1989. 10(6): 
p. 677-82. 
33. 
Fang, J., et al., Association of sleep duration and hypertension among US adults varies by 
age and sex. Am J Hypertens, 2012. 25(3): p. 335-41. 
34. 
Mourtazaev, M.S., et al., Age and gender affect different characteristics of slow waves in 
the sleep EEG. Sleep, 1995. 18(7): p. 557-64. 
35. 
Redline, S., et al., The effects of age, sex, ethnicity, and sleep-disordered breathing on 
sleep architecture. Arch Intern Med, 2004. 164(4): p. 406-18. 
36. 
Van Cauter, E., R. Leproult, and L. Plat, Age-related changes in slow wave sleep and 
REM sleep and relationship with growth hormone and cortisol levels in healthy men. 
Jama, 2000. 284(7): p. 861-8. 
37. 
Heinzer, R., et al., Slow-wave activity in sleep apnea patients before and after continuous 
positive airway pressure treatment: contribution to daytime sleepiness. Chest, 2001. 
119(6): p. 1807-13. 
38. 
Dijk, D.J., Slow-wave sleep deficiency and enhancement: implications for insomnia and 
its management. World J Biol Psychiatry, 2010. 11 Suppl 1: p. 22-8. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 30 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
39. 
Liu, Y., et al., Sleep duration and chronic diseases among U.S. adults age 45 years and 
older: evidence from the 2010 Behavioral Risk Factor Surveillance System. Sleep, 2013. 
36(10): p. 1421-7. 
40. 
Philip, P., et al., Acute versus chronic partial sleep deprivation in middle-aged people: 
differential effect on performance and sleepiness. Sleep, 2012. 35(7): p. 997-1002. 
41. 
Bellesi, M., et al., Enhancement of sleep slow waves: underlying mechanisms and 
practical consequences. Front Syst Neurosci, 2014. 8: p. 208. 
42. 
Rosenberg, R.P., Sleep maintenance insomnia: strengths and weaknesses of current 
pharmacologic therapies. Ann Clin Psychiatry, 2006. 18(1): p. 49-56. 
43. 
Benca, R.M., Diagnosis and treatment of chronic insomnia: a review. Psychiatr Serv, 
2005. 56(3): p. 332-43. 
44. 
Arbon, E.L., M. Knurowska, and D.J. Dijk, Randomised clinical trial of the effects of 
prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during 
sleep in healthy people. J Psychopharmacol, 2015. 29(7): p. 764-76. 
45. 
Keklund, G. and T. ÅKerstedt, Objective components of individual differences in 
subjective sleep quality. Journal of Sleep Research, 1997. 6(4): p. 217-220. 
46. 
Doshi, V., et al., STOP-BANG questionnaire as a screening tool for diagnosis of 
obstructive sleep apnea by unattended portable monitoring sleep study. SpringerPlus, 
2015. 4: p. 795. 
47. 
Basner, M., D. Mollicone, and D.F. Dinges, Validity and Sensitivity of a Brief 
Psychomotor Vigilance Test (PVT-B) to Total and Partial Sleep Deprivation. Acta 
Astronaut, 2011. 69(11-12): p. 949-959. 
48. 
Van Dongen, H.P., et al., The cumulative cost of additional wakefulness: dose-response 
effects on neurobehavioral functions and sleep physiology from chronic sleep restriction 
and total sleep deprivation. Sleep, 2003. 26(2): p. 117-26. 
49. 
Akerstedt, T. and M. Gillberg, Subjective and objective sleepiness in the active 
individual. Int J Neurosci, 1990. 52(1-2): p. 29-37. 
50. 
Kaida, K., et al., Validation of the Karolinska sleepiness scale against performance and 
EEG variables. Clin Neurophysiol, 2006. 117(7): p. 1574-81. 
51. 
SW., S. and P. LP., Estimating aircrew fatigue: a technique with application to airlift 
operations, in Technical report SAM-TR-82-21. 1982, USAF School of aerospace 
medicine: Brooks AFB, TX. 
52. 
Monk, T.H., A Visual Analogue Scale technique to measure global vigor and affect. 
Psychiatry Res, 1989. 27(1): p. 89-99. 
53. 
Babkoff, H., T. Caspy, and M. Mikulincer, Subjective sleepiness ratings: the effects of 
sleep deprivation, circadian rhythmicity and cognitive performance. Sleep, 1991. 14(6): 
p. 534-9. 
54. 
Carskadon, M.A. and W.C. Dement, The multiple sleep latency test: what does it 
measure? Sleep, 1982. 5 Suppl 2: p. S67-72. 
55. 
Arand, D. and M. Bonnet, Appendix II, in Sleep Disorders. 2008, CRC Press. p. 658-668. 
56. 
Johns, M.W., A new method for measuring daytime sleepiness: the Epworth sleepiness 
scale. Sleep, 1991. 14(6): p. 540-5. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 31 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
57. 
Bastien, C.H., A. Vallieres, and C.M. Morin, Validation of the Insomnia Severity Index as 
an outcome measure for insomnia research. Sleep Med, 2001. 2(4): p. 297-307. 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 32 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
APPENDIX I 
The sleep center environment is important to the conduct of this study. It is the trial be 
conducted under highly controlled conditions for the polysomnography recording and 
PowerSleep device. The participant rooms of the sleep center should operate with the 
same or similar controls for sound and lighting conditions as required by the American 
Academy of Sleep Medicine Accreditation Standards. The sleep recording bedrooms 
should be quiet and guarded from of disturbing noise in the surrounding area. Lighting 
control in bedrooms should be available for the attending technologists and/or 
coordinators. A single “night-light” is permissible; the light should not be in direct line of 
sight for the participant, and should not exceed 7 Lux. Audio and video monitoring of the 
participants during the sleep periods is recommended, however, recording the 
audio/visual is not allowed.  Staff should conduct the testing procedures in the same 
manner as those requirements during clinical recordings. Room entry and operationally-
related disruptions should be minimized, and should occur on a last-available-option 
basis.  
Participants should wear comfortable loose bed clothing while in the sleep center. They 
should arrive to the sleep center with sufficient time to complete all required documents, 
change clothing, and generally acclimate to their assigned room for the night. 30 
minutes prior to Lights Out the technologist will help the participant put on the 
PowerSleep Device.  Once the device is on the head the technologist will connect it to 
the provided study laptop for an impedance check.  If the software detects any issues 
electrodes may need to be repositioned or replaced.  If the software detects no issues 
the participant will be able to continue with their bedtime routine before lights out. If 
during the course of the overnight stay, a software alert is generated regarding the 
PowerSleep device impedance, the technologist should follow the instructions in the 
prompt, which may include adjusting the electrodes. 
If the participant should need to use the restroom during the night, they should be 
instructed to speak up and wait for the technologist to assist them in getting out of the 
bed. They may also need to assist the participant with getting back into the bed so as to 
avoid removing the PowerSleep device.   If the PowerSleep device does come off or 
becomes disconnected from the user interface, the technologist will provide new 
electrodes if necessary and will reconnect the user interface.  
 
 
 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 33 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
APPENDIX II 
The MSLT will consist of four trials conducted at approximately two-hour intervals 
beginning 2 hours after wake time +/- 5 minutes. 
 
The research version of the MSLT will be performed. 
 Each trial will be terminated after 2 to 3 consecutive minutes of sleep have 
occurred OR after 20 minutes, whichever occurs first. 
 Sleep latency is defined as the time from the start of the trial (“Lights Off”) to the 
first of three consecutive epochs (30-second epochs) of unambiguous stage N1 
OR one epoch of N2, N3, or REM. (If three consecutive epochs consist of N1-
N1-N2, sleep latency is the first epoch of N1. If three consecutive epochs consist 
of N1-N2-W, sleep latency is the N2 epoch). If sleep latency criteria is not met 
within 20 minutes, the sleep latency is defined as 20 minutes. 
 IMPORTANT:  Trials should not be terminated until the technologist is absolutely 
certain that sleep onset has occurred. Continue the trial to collect an additional 
2-3 consecutive minutes of sleep if unsure.  
 
MSLT protocol 
1. The MSLT should be conducted by an experienced technologist. 
2. Conventional recording montage including EEG (F3-M2, F4-M1, C3-M2, C4-M1, 
O1-M2, O2-M1), EOG (E1-M2, E2-M2), submental EMG, and ECG should be 
used. 
3. Subjects should wear comfortable clothing and remove shoes/slippers prior to 
each trial. 
4. Subjects should be instructed to use the restroom prior to each trial. 
5. Subjects should be instructed to turn off electronics prior to each trial. 
6. Perform bio-calibration before each trial to ensure the integrity of the recording 
signals. Leads should be replaced, if necessary, prior to the start of the trial. 
7. Standard instructions for bio-calibrations: 
 
 
“Lie awake with your eyes open until my next instruction.”  (30 seconds) 
“Close your eyes but remain awake until my next instruction.” (30 
seconds) 
 
 
“Open your eyes and look straight ahead.” 
“Without moving your head, look to the right”, <pause>, “look to the left” 
<pause>, “look to the right”, <pause>, “look to the left”. <pause> “look up”, 
<pause>, “look down”, <pause>, “look up”, <pause>, “look down”. 
 
 
“Blink slowly 5 times.” 
 
 
“Grit your teeth” (or “Stick out your tongue.”) 
8. Just prior to start of trial:  “Please lie quietly, keep your eyes closed and try to fall 
asleep.” 
9. Stop the trial after 2-3 consecutive minutes of sleep have occurred OR after 20 
minutes, whichever occurs first. 

 
 
 
Protocol #AI-16128-PSPIV-LO 
Page 34 of 34 
09/18/2017 ver 2.0 
 
 
Confidential  
  
 
10. An experienced technologist or individual designated by the principal investigator 
should review and score sleep latency. 
11. Record on source document:  Trial number, start time (“lights off”), stop time 
(“lights on”), site scored sleep latency. 
 
 
What to do if: 
 If a trial is interrupted (e.g. emergency bathroom break, fire alarm, patient safety 
issue, no readable EEG tracing) re-start the test, and document the issue and 
timing. Interrupting a trial can cause invalid data and should be avoided if at all 
possible.   
 If the subject moves more than 50% of two consecutive epochs, the technologist 
should instruct the subject to “Please lie still.” 
 If the subject persistently opens eyes, the technologist should instruct the subject 
to “Please keep your eyes closed.”