The Impact of Suvorexant on Cognitive Function and Daytime Symptoms Among Community-dwelling Older Adults With Insomnia: A Placebo-controlled, Randomized Clinical Trial Using Remote Monitoring and Ecological Momentary Assessment
Phase: PHASE2
Conditions: Insomnia
Sponsor: University of Maryland, Baltimore

RESEARCH PROTOCOL 
 
Title: The impact of suvorexant on cognitive function and daytime symptoms among 
community-dwelling older adults with insomnia: A placebo-controlled, randomized clinical 
trial using remote monitoring and ecological momentary assessment 
 
Principal Investigator: Emerson Wickwire, PhD 
 
Date: 16 September, 2025 
 
NCT: NCT05908526 
 
Lay Summary 
The purpose of this study is to employ ecological momentary assessment (EMA) methods 
to evaluate the impact of suvorexant on alert cognition and daytime symptoms among 
community-dwelling older adults with insomnia. 
 
Traditional assessment methods such as retrospective questionnaires or standard 
neurocognitive tests enable measurement of symptoms at one point in time, in a research 
environment. By contrast, remote monitoring approaches such as ecological momentary 
assessment (EMA; e.g., administered via mobile device) enable ongoing, data-rich 
assessment of symptoms such as cognitive alertness, fatigue, and low mood in 
participants’ natural environments. 
 
Speciﬁc Aims 
The long-term goal of this research is to improve outcomes for patients with sleep 
disorders. The overall objective of the current application is to test preliminarily remote 
monitoring and ecological momentary assessment (EMA) methods for measuring the 
impact of insomnia treatment on daytime symptoms (i.e., to employ EMA as an outcome 
measure). Based on prior research, our central hypothesis is that relative to placebo, 
suvorexant improves daytime insomnia symptoms as assessed via EMA. 
 
Speciﬁc Aim 1: To employ ecological momentary assessment (EMA) methods to evaluate 
the impact of suvorexant on daytime insomnia symptoms among community-dwelling 
older adults with insomnia. 
 
Hypothesis 1: Relative to placebo, suvorexant improves alert cognition and daytime 
symptoms as assessed via EMA. 
 
Design 
This is a single-site, double-blind, randomized, placebo-controlled clinical trial. The study 
employs a two-group (suvorexant, 20mg, qhs, versus placebo) parallel design and involves 
remote (baseline) assessments, 16-day active treatment phase with intensive ambulatory 
monitoring via wrist actigraphy and ecological momentary assessment (EMA). Outcome 

assessments are conducted at two weeks while participants are on study treatment or 
placebo and include self- report questionnaires and comprehensive cognitive testing 
administered by computer. 
 
STUDY PROCEDURES 
Recruitment 
Participants will be recruited to the study in several ways (i.e., volunteer lists, mailings 
based on EPIC searches, newspaper advertisements, online and social media 
advertisements, public presentations, and word of mouth and study ﬂiers at the University 
of Maryland Sleep Disorders Center, Midtown Campus). Approaches to recruitment are 
described in “Recruitment” section below. 
 
Self-Screening Form Process 
In all recruitment pathways except for online and social media advertisements, the 
participants will be provided with study sta_ contact information, and the participant will 
call (or video chat, if requested) with study sta_ to be screened for the study. 
For online and social media, advertisements, and recruitment pathways, the participants 
will be provided with study sta_ contact information. If interested in the study, the 
participant will complete an online preliminary screening questionnaire prior to being 
phone-screened. If individuals meet the initial study criteria via preliminary screening, then 
the information will be sent to the recruitment team for review before contacting the 
participant via phone. 
 
Phone Screening 
Interested participants will speak remotely e.g., over the phone or via secure 
teleconferencing platforms like Zoom with study sta_ to conﬁrm high likelihood of 
insomnia and low risk for major untreated medical, psychiatric, and other sleep disorders. 
This screening will assess all eligibility criteria (e.g., age, sleep di_iculties, substance use, 
existing medical conditions) in addition to conﬁrming that the volunteer will be available 
locally during the course of the study (i.e., conﬁrming that the volunteer will not be traveling 
during the duration of the study). Individuals who pass the initial screening will be invited to 
complete remote assessments with trained project sta_ to conﬁrm eligibility for the study. 
Given that participants will be older adults, project sta_ will provide technical assistance 
whenever possible. 
 
Eligibility/Consenting/Phone Call 
Participants will receive the study consent form via email (or via snail mail if requested). 
The study team will work with potential participants to complete the informed consent 
process. Participants will provide their signed consent to participate in the study. Once 
signed consent is conﬁrmed, participants will complete the remote assessments. Then the 
study sta_ will conﬁrm eligibility and the sleep expert (i.e., PI) will conﬁrm individual’s study 
participation. 
 

Once study participation is conﬁrmed, the participant will be randomized to drug or 
placebo in a 1:1 ratio by the IDS pharmacy. Throughout the study participants will wear an 
actigraph. An actigraph is a wristwatch-like device that detects ambulatory movement, a 
validated proxy for sleep. Participants will also complete brief surveys four times per day 
for 16 days. At post-treatment, participants will complete validated questionnaires, 
neurocognitive tasks, and a brief satisfaction survey. Additional details presented below. 
Remote Assessments (Day 0) 
Study sta_ will schedule a time for participants to complete the remote assessments. 
These include a semi-structured interview, validated questionnaires (about 45-60 
minutes), and computerized neurocognitive tasks (about 15-20 minutes). 
Participants will complete the remote assessments over one day (90 minutes) or two days 
(about 45 minutes each day). For participants who prefer to complete the remote 
assessments over two days, the ﬁrst day will include the consent and interview. The 
second day will include the validated questionnaires and neurocognitive tasks.  
 
Participants use a special research smartphone app for this study, which will capture daily 
surveys (described below). All study tasks will be remote, e.g., over the phone or via secure 
teleconferencing platforms like Zoom. During the remote assessments, participants will 
have many breaks to help them stay refreshed. Participants can also request a break after 
any task. 
 
Neurocognitive tasks are computerized measures that include the psychomotor vigilance 
test (PVT), Stroop Task, and a Task-switching exercise developed for use among older 
adults. To help participants complete these tasks, study sta_ will email or text participants 
a link, which will enable completion of the computerized tasks on participants’ 
smartphone, laptop, or desktop computer. In the tasks participants will be asked to 
respond to words, shapes, and colors on their screens. 
 
Home Sleep Apnea Test (Day 0) 
Participants will complete a Home Sleep Apnea Test (HSAT) early in the study to evaluate 
their breathing during sleep. The HSAT will determine if participants have obstructive sleep 
apnea (OSA). The HSAT device will be mailed to participants by a third-party company 
supporting this study. Participants will follow instructions on how to use the device. 
Participants will return the device using a pre-paid return mailing envelope. Participants 
will have 24-hour support if needed. 
 
Actigraphy Setup (Days 1-16) 
Once participants complete the remote assessments participants will set up their 
actigraph with study sta_. Study sta_ will contact participants to review instructions and 
inquire of general questions of quiet time activities remotely e.g., over the phone or via 
secure teleconferencing platforms like Zoom. Participants will be instructed to wear an 
actigraph on their non-dominant hands for approximately 16 days. We will mail 
participants an actigraph along with a pre-paid mailing envelope. Actigraphs are expensive 

research devices and must be returned. Study sta_ will call to remind participants when it 
is time to return the actigraph. 
 
Daily Survey Completion (Days 1-16) 
While participants wear the actigraph, they will also complete brief surveys on their mobile 
phones. The surveys are sent to participants 4 times a day for 16 days. Each survey takes 
less than 2 minutes to complete. Participants' phones will send them notiﬁcations for each 
survey. At the start of the study, participants will choose what time they want surveys to 
start. Every morning, participants will complete a survey that includes a brief sleep diary 
and questions about generalized quiet time activities and how they feel. Next, participants 
will complete three more surveys throughout the day. These surveys also ask about how 
they feel. These surveys will be given at random times throughout the day, about two hours 
apart over the next 12 hours. Study sta_ will be available to answer any questions or give 
support. Contact information for study sta_ and technical support will be given to them. 
 
Post Assessments (Prior to Day 16) 
Study sta_ will schedule a time for participants to complete the post-assessment before 
discontinuing study drug or placebo. These assessments include validated questionnaires 
(about 45-60 minutes), computerized neurocognitive tasks (about 15-20 minutes), and a 
brief satisfaction survey 
 
Unique Identiﬁers 
Study sta_ will assign each participant a unique 4-digit identiﬁcation number, generated by 
an online random integer generator. Any information linking the subject ID to PHI will be 
kept in the master/coded list, which will be stored virtually in a limited access, password-
protected drive on UMB-encrypted devices. The folder with all participant PHI will be 
accessible only to trained study sta_ authorized by the PI to access these ﬁles. 
 
Neurocognitive Testing 
General neurocognitive function will be assessed by using computerized testing which can 
be completed via a software package developed speciﬁcally for remote administration. 
Measures to be administered include sustained attention (psychomotor vigilance task 
[PVT]), inhibition (Stroop task), and task-switching/executive function (task-switching task). 
Participants will receive a link to complete the neurocognitive tasks. These tasks can be 
completed in approximately 15-20 minutes via smartphone, laptop, or desktop computer. It 
should be noted that no PHI will be entered or transmitted, participants will be identiﬁed 
using only a participant ID. 
 
Training in EMA and Actigrpahy 
Participants will be trained on how to use a secure mobile app, like RealLife Exp (by 
LifeData), which includes ecological momentary assessment (EMA) functionality. App 
versions for iOS and Android are available. As indicated above, participants will also be 
instructed on the proper use of a research actigraph and provided such device via tracked 
mail (e.g., FedEx) speciﬁc registration and data coding procedures are presented below: 

1. Participants will be provided an actigraph, in addition to receiving training in using the 
mobile app. 
2. Participants will be provided a reminder card as well as contact information for the study 
sta_, should any questions arise during the study. 
3. Trained study sta_ will instruct participants in detail regarding each step of the study, so 
that participants always know what to expect. 
 
Insomnia Treatment-Suvorexant (FDA-Approved) 
All packaging label-insert instructions and guidelines will be followed at all times during 
this study. 
 
Eligible participants will be initiated on 10mg suvorexant (or placebo), po, qhs, including 
instructions on dosage, expectations, and potential side e_ects. Following this two-day 
period, individuals in the treatment condition will be increased to 20mg for a 14-day active 
treatment period (i.e., 16 nights taking a pill). 
 
Individuals in the control condition will continue with placebo (16 nights taking a pill). 
Consistent with the Model Study Agreement and UMMC IDS Pharmacy policies and 
procedures, robust safety measures will be followed and, study sta_ will contact the 
participant after staring Suvorexant (or placebo). 
 
Home Sleep Apnea Test (HSAT) 
All eligible participants will undergo HSAT to evaluate sleep-disordered breathing. HSAT 
will be administered by a third-party provider, CleveMed. For individuals recruited from 
various sleep disorders center (including those who already have an OSA diagnosis and 
use a CPAP device) will have previously been referred for overnight polysomnography (PSG) 
or HSAT as part of their routine clinical care. These individuals may not be required to 
complete an HSAT; with participant consent, the presence of OSA for this study will be 
based on clinical PSG (or HSAT) ﬁndings. 
 
SAMPLE SIZE AND DATA ANALYSIS 
Sample Size 
The DISS will serve as our primary endpoint, and the power/sample size analysis is based 
on this primary endpoint. Our mixed model approach depends on the size of the intra class 
correlations (ICC) between repeated measures. Based on results from our prior research), 
with a sample size of 20 completers each arm and 20% attrition rate, we would have the 
power of 0.92 to detect a medium e_ect size of Cohen’s d=0.5 based on simulation 
analysis at the α level of 0.05. Given the measurement sensitivity of our approach, we 
anticipate su_icient power to detect di_erences between groups for both cognitive and 
sleep outcomes. 
 
Multiple corrections will be performed at the critical p-values of 0.05, 0.025, and 0.017 to 
show minimum and maximum sensitivities using the false discovery (FDR) method, which 

is contingent upon the number of outcome measures that exceed these given critical 
values. 
 
Statistical Analysis Plan 
All statistical analyses will be performed using the intention to treat principle; all subjects 
enrolled and randomized will be accounted for in the ﬁnal analysis in their randomized 
group. 
 
Main Analysis  
The Primary Endpoint (PE) is the between-group di[erence (SUV vs PBO) in each DISS 
subscale at four EMA time-of-day assessments (Morning, Midday, Afternoon, Evening) 
across the study period. Based on our current MISP, we anticipate high adherence with 
>80% completion of all assessments. We will ﬁt linear mixed-e[ects models for each 
subscale, including ﬁxed e[ects for Group, Time of Day, Day (1–16 continuous), age, and 
sex; and a random intercept for each participant. The Group×Time interaction will be 
evaluated using a 4-degree-of-freedom Wald test to determine whether suvorexant and 
placebo di[er at any time of day. If needed, the generalized additive model (GAM) will be 
used to account for the non-linear time e[ects. Covariates will be limited to age and sex at 
birth. Multiple imputation will be implemented for missing data; to conﬁrm the 
assumptions of multiple imputation that data is missing at random, we will perform 
sensitivity analyses. 
 
Secondary Analyses 
To examine the e_ects of treatment with each secondary EMA endpoint including 
fatigue/sleepiness, positive a_ect, and negative a_ect, we will employ the model described 
above (i.e., same approach as used in the primary analysis). To examine the e_ects of 
treatment on 1) sleep continuity variables (sleep onset latency, wake after sleep onset, 
sleep e_iciency, and total sleep time) as measured by sleep diary and actigraphy, 2) self-
report questionnaires, and 3) cognitive testing, scores will be compared both within and 
between-groups adjusting for baseline values using analysis of covariance (ANCOVA). This 
procedure is known to maximize power. 
 
Post Assessment 
Post Assessment Satisfaction Survey: A brief user experience/satisfaction survey will be 
administered to participants following the completion of the 16-day continuous monitoring 
phase. 
 
Safety Monitoring 
If a potential participant indicates thoughts of self harm, they will administratively 
withdrawn from the study. These individuals will be referred to the Carruthers 
Clinic/Outpatient Mental Health at the UMMC-Midtown Campus, as well as advised to 
contact their primary care providers (or mental health professional if they have one), to call 
or text the national suicide hotline directly at 988 (or 800-273-8255), 911, and/or to report 

to their nearest emergency room. For all withdrawals due to thoughts of self-harm, the PI 
will follow-up to ensure this was done, or that adequate alternative steps were taken. 
Participants who are withdrawn from the study will be compensated for study procedures 
completed. 
 
NEUROCOGNITIVE TESTING 
Assessments 
General neurocognitive function will be assessed by using computerized testing which can 
be completed via a software package developed speciﬁcally for remote administration. 
Measures to be administered include sustained attention (psychomotor vigilance task 
[PVT]), inhibition (Stroop task), and task-switching/executive function (task-switching task). 
Participants will receive a link to complete the neurocognitive tasks. These tasks can be 
completed in approximately 15-20 minutes via smartphone, laptop, or desktop computer. It 
should be noted that no PHI will be entered or transmitted, participants will be identiﬁed 
using only a participant ID. 
 
To complete the three computerized tasks (Stroop, PVT, Task-Switch), participants will be 
emailed the link to download each task. Study sta_ will instruct participants on how to 
download the link and open the tasks on their home computer. Once the task is open, it will 
prompt participants to enter their unique ID. Study sta_ will stay on the phone with 
participants for the duration of the computerized tasks to provide technical support if 
needed. After participants complete each computerized task, their data will be 
automatically sent to the researchers. Participants will have breaks in between each 
individual task and based on participant need. 
 
RECRUITMENT 
Inclusion/Exclusion Criteria 
Inclusion 
1. Age 60-85 years old. 
2. Meets Diagnostic and Statistical Manual – Fifth Edition (DSM-5) diagnostic criteria for 
chronic insomnia disorder. 
 
Exclusion 
1. High risk for untreated organic sleep disorders other than insomnia (narcolepsy, periodic 
limb movement disorder, etc) as determined by structured clinical interview and 
investigator clinical judgment. 
2. Current diagnosis of an untreated major medical (e.g., diabetes, heart disease) or 
psychiatric (e.g., bipolar disorder) disorders. 
3. History of suicide attempt within past 5 years. 
4. History of alcohol or substance abuse (including prescription medication abuse) within 
past 5 years.  
5. Heavy alcohol consumption (e.g., >5 drinks per day or > 14 drinks per week). 
6. Heavy ca_eine use (>4 cups of co_ee/day [equivalent]).  
7. Current tobacco or nicotine use. 

8. History of previous allergic reaction, sensitivity, or severe side e_ects to sedative 
hypnotics.  
9. Moderate/strong CYP3A inhibitors. 
10. Refusal to discontinue or intent to initiate non-study prescription, OTC, or other sleep 
aids during study period.