Clinical trial NCT02704754
Conditions: Insomnia Posttraumatic Stress Disorder
Sponsor: Howard University
Start date: 2016-05-01; Completion date: 2021-04-30
Enrollment: 41 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved drugs has a unique mechanism of action that may be well suited for targetting arousal at night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for insomnia that developed in relation to trauma exposure, utilizing a placebo control, and polysomnography to identify biomarkers of response, in a six week trial.

Detailed description:
Disturbed sleep is one of the most common and distressing responses to exposure to severe trauma and can persist in many of those affected with and without accompanying posttraumatic stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are prevalent in trauma-exposed populations including PTSD, depression, and physical health conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not typically differentiated in studies characterizing insomnia and its treatment, and insomnia accompanying PTSD has been shown to be relatively refractory to the treatments that are established for PTSD. Thus treatment of TRI presents an unmet need that has implications for the large and growing groups of people exposed to trauma in terms of relieving distress and preventing further psychiatric and medical morbidity.

Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD is developing, and during its more acute stages. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists dampen the activity of a specific arousal enhancing system in the brain during sleep. In rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow wave and REM activity (in contrast with traditional hypnotics which can diminish both). Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and its tolerability in these populations. We will include polysomnography (PSG) in order to have objective sleep outcomes and probe potential mechanisms and biomarkers predicting response. The proposed study will meet the objective below and test the following hypotheses:

Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for insomnia and who identify a severely threatening event (DSM criterion A trauma) as a precipitant or a factor that significantly exacerbated their sleep disturbance.

The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of sleep efficiency will be increased in the group receiving suvorexant compared with the group receiving placebo.

The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated.

Exploratory analyses will include comparison of response patterns among those with versus without significant symptoms of PTSD and relationships between increased in slow wave and rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms.

Adverse experiences and the tolerability of suvorexant in the recruited population with TRI will also be evaluated.

Arms: arm 1: 10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime. arm 2: A pill without active ingredients

Randomization occurs 1:1 with stratification for gender and PTSD status.
Interventions: intervention 1: suvorexant intervention 2: placebo
Intervention descriptions: intervention 1: First in class orexin antagonist recently approved by the FDA for the treatment of insomnia intervention 2: Pill with inactive ingredients

Protocol documents:
Prot_SAP_000.pdf: 
      MISP Template: Protocol 
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Final Version: 8/13/2010 
 
 
 
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MIISSPP))  
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Requirements for Submitting a Full Proposal 
 
 
Section #1 - MISP Protocol Identification 
 
Study Title: 
  
Suvorexant and Trauma-related Insomnia 
(A placebo controlled trial with polysomnography)  
Request Date: 
 
6/22/15   Revised 9/17/18 
Institution Name 
 
Howard University  
Investigator 
Contact 
Information: 
- Full address  
- Phone No. 
- Fax  No. 
- e-mail address 
 
Thomas A. Mellman, MD 
Howard University College of Medicine 
520 W St, NW 
Washington DC, 20059 
202-806-7820 
202-806-5677 
Tmellman@Howard.edu 
 
 
 
 
 
 


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Section #2- Core Protocol 
 
2.1 Objectives & 
Hypotheses  
 
 
 
 
Disturbed sleep is one of the most common and distressing responses to 
exposure to severe trauma and can persist in many of those affected with 
and without accompanying posttraumatic stress disorder (PTSD). Insomnia is 
a risk factor for many of the conditions that are prevalent in trauma-exposed 
populations including PTSD, depression, and physical health conditions such 
as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not 
typically differentiated in studies characterizing insomnia and its treatment, 
and insomnia accompanying PTSD has been shown to be relatively 
refractory to the treatments that are established for PTSD. Thus treatment of 
TRI presents an unmet need that has implications for the large and growing 
groups of people exposed to trauma in terms of relieving distress and 
preventing further psychiatric and medical morbidity.  
Most of the data on TRI comes from research on populations with PTSD. 
Difficulty initiating and maintaining sleep is designated as one of the 
heightened arousal symptoms of PTSD in the DSM. Sleep studies have 
suggested reduced slow wave sleep (SWS) in some PTSD populations and 
fragmented rapid eye movement (REM) sleep when PTSD is developing, and 
during its more acute stages. Suvorexant is a first in class orexin antagonist 
and is approved by the FDA for the indication of insomnia. Orexin 
antagonists dampen the activity of a specific arousal enhancing system in the 
brain during sleep. In rodent models suvorexant has been shown to enhance, 
and in healthy humans, to not affect slow wave and REM activity (in contrast 
with traditional hypnotics which can diminish both). Reducing arousal during 
sleep while maintaining REM and slow wave sleep is a promising profile for 
the treatment of TRI. We are therefore proposing a placebo controlled 
evaluation to assess the efficacy of suvorexant for treating TRI with and 
without PTSD and its tolerability in these populations. We will include 
polysomnography (PSG) in order to probe potential mechanisms and 
biomarkers predicting response. The proposed study will meet the objectives 
below and test the following hypotheses:    
Objective 1. To recruit a group of participants that meet criteria for insomnia 
and who identify a severely threatening event (DSM criterion A trauma) as a 
precipitant or a factor that significantly exacerbated their sleep disturbance; 
and to determine the frequency of PTSD diagnoses and symptoms among 
the recruited participants. 
            Hypothesis 1) – Recruitment will reveal TRI to be a common 
condition that in approximately half of cases occurs absent PTSD.  
 
Objective 2. To evaluate the effectiveness and tolerability of suvorexant on 
insomnia and when present, associated PTSD symptoms and its effects on 
PSG measures in participants with TRI. 
 
Hypothesis 2a) Insomnia will improve, and nightmares and other 
PTSD symptoms will be reduced with suvorexant treatment compared with 
placebo.  
 
2b) Improved sleep will be associated with reduced non-sleep related 
PTSD symptoms when present.  


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2c) Suvorexant will be well tolerated by the participants.  
 
2d) Sleep latency and wake after sleep onset (WASO) will be reduced 
with suvorexant treatment compared with placebo.  
           2e) (exploratory hypothesis) When reduced at baseline (i.e. SWS 
below 100 minutes and mean REM segment duration below 15 minutes) 
SWS and the duration of continuous segments of REM sleep will increase 
with suvorexant compared with placebo.          
 
2.2 Background & 
Rationale, 
Significance of 
Selected Topic & 
Preliminary Data  
 
Trauma-Related Insomnia (TRI) 
Insomnia is a common sequela of trauma exposure. In a review of studies of 
populations exposed to disasters, “trouble sleeping” was the most common 
symptom reported, especially from studies where sampling occurred within 4 
months.1 Findings from the Millennium Cohort Study indicated that military 
personnel who had been deployed to Afghanistan and/or Iraq were 14 – 29% 
more likely to report insomnia symptoms compared with those who had not 
been deployed, and 27% of the post-deployment personnel reported 
insomnia symptoms that were at least moderately severe.2  Krakow and 
colleagues3 found that 99% of 78 treatment seeking evacuees of the Cerro 
Grande Fire met criteria for “psychophysiological” insomnia. Rates of 
insomnia for veterans and civilians with PTSD, have ranged from 70 to 
91%.4-6 When both have been reported, the rates for insomnia in trauma 
exposed populations exceed those for PTSD (e.g. PTSD rates for the 
Millennium Cohort were estimated at 5%,2 in the group recruited by Krakow 
et al. the rate for PTSD was 59%3). In our recent report of 136 urban young 
adult African Americans, 83% were trauma exposed, 16% met full criteria for 
current PTSD, and 43% exceeded a recommended threshold score for 
diagnosing insomnia (Insomnia Severity Index score of 10 or greater7).8  
TRI may often endure when other PTSD symptoms have remitted. For 
example, Zayfert and DeViva9 reported that 48% of patients who achieved 
remission of PTSD following CBT developed for PTSD continued to 
experience insomnia indicating that Further evidence that TRI represents an 
important treatment need comes from an analysis by the applicant and 
collaborators of a state Medicaid data base which revealed that over half of 
patients with a PTSD diagnosis taking psychopharmacologic medications 
were receiving various hypnotics.10  
Polysomnographic findings in TRI  
Studies with objectively recorded sleep in TRI have generally been in the 
context of PTSD. A meta-analysis of PTSD sleep studies published in 2007 
by this application’s co-PI revealed “lighter sleep” in terms of reduced SWS 
and increased stage 1 as well as increased frequency of eye movements 
during REM sleep (REM density).11 Much of the focus of such research has 
been on REM sleep. This interest was initially inspired by hypothesized 
abnormalities of REM sleep based on the occurrence of recurring nightmares 
that (to varying degrees), replicate past (traumatic) experiences.12 Dreams 
most commonly arise from REM sleep and do not normally represent 
unaltered memories of specific events.13,14 More recently investigators have 
postulated that REM sleep (when not disrupted) provides conditions that are 
conducive to reducing the affective intensity of trauma memories and 


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facilitating their integration into overall autobiographical memory.15 
 
Studies have not found consistent alterations in the latency to, or amounts of, 
REM sleep with PTSD. The increased REM density that was confirmed in the 
aforementioned meta-analysis11 has also been reported in association with 
trauma exposure absent PTSD.16 In this study that uniquely reported PSG 
findings from the early aftermath of trauma the length of uninterrupted 
segments of REM sleep were shorter among the injured patients developing 
PTSD.16 Of all of the PSG measures examined, this index of REM sleep 
fragmentation also demonstrated the strongest correlation with insomnia 
symptoms (i.e. stronger than the correlations with total sleep duration or 
WASO).16  Reduced and fragmented REM sleep was also noted anecdotally 
in a report of sleep in association with acute combat fatigue.17 Symptomatic 
awakenings in PTSD, with and without nightmares, have been shown to be 
preceded by, and thus could be considered to disrupt REM sleep.18,19 Such 
awakenings have been noted to occur less frequently in laboratory settings 
than in naturalistic environments and laboratory sleep studies of PTSD have 
not consistently demonstrated reduced or fragmented REM sleep. Our recent 
report provides some perspective on this apparent inconsistency in 
documenting an inverse relationship between several indices of REM 
duration and continuity and the duration of PTSD. This report also noted that 
the tendency for REM sleep to be suppressed or disrupted with PTSD of less 
chronic duration is also consistent with the overall findings in the literature.20 
Thus, while reducing insomnia and improving sleep is an important goal for 
distressed trauma-exposed individuals, maintaining the continuity of REM 
sleep may be of particular significant to interventions applied within a few 
years of trauma exposure in alleviating insomnia symptoms.               
 
Rationale for suvorexant 
 
Orexin antagonists are a new class of therapeutic agents that are promising 
for diminishing arousal to maintain overall sleep and specifically REM sleep. 
Orexin is implicated in coordinating brain stem centers that initiate and 
maintain states of arousal and are deficient in narcolepsy, a disorder with 
excessive and disinhibited REM sleep.21 The Merck product suvorexant is a 
dual orexin receptor antagonist and the first and to date only FDA approved 
agent from this class.21 Results of the 2, pivotal 3 month trials involving over 
2000 patients22 have been reported as well as a 1 year trial where 522 
patients received suvorexant.23 Suvorexant has shown consistent efficacy in 
reducing insomnia, and in reducing WASO and latency to persistent sleep in 
people with primary diagnoses of insomnia. It has also been well tolerated 
with somnolence being the most common adverse effect, endorsed by 7% of 
insomnia patients receiving approved doses versus 4% of those receiving 
placebo. Only 3% of trial participants receiving suvorexant discontinued 
treatment due to adverse effects which was comparable to the rate for those 
receiving placebo. Of note, despite targeting a system that is implicated in 
narcolepsy, there were no incidences of cataplexy observed in these clinical 
trials. Orexin antagonists have been shown to increase REM and SWS in 
animal models, however, in healthy humans (without disturbed sleep) there 
were no significant changes in the amount of REM sleep nor changes in the 
distribution of spectral EEG frequencies within each sleep stage.21 Based on 


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these data we predict that suvorexant will not precipitate REM sleep-related 
parasomnias in the proposed target population but rather will consolidate 
fragmented REM sleep periods that have been observed  in the earlier 
stages of PTSD. This would be similar to the effects seen for the alpha 1 
adrenergic antagonist prazosin, an agent that targets central noradrenergic 
arousal promoting mechanisms and has been shown to reduce the severity 
of nightmares and related sleep disruption with PTSD. Specifically, the only 
study that monitored EEG sleep found lengthened discreet REM sleep 
periods with increases in the amount of REM sleep that were proportionate to 
the increases in overall sleep time. Prazosin, however, did not reduce time to 
fall asleep in this study.24 Given the data from animals and that the absence 
of changes was in healthy volunteers, we hypothesize that suvorexant will 
also enhance SWS when it is deficient at baseline.  
Summary of Significance 
Insomnia is quite common among those exposed to trauma. PTSD usually 
features insomnia symptoms and insomnia precipitated or exacerbated by 
trauma is also common absent a PTSD diagnosis. TRI does not appear to 
respond well to previously available treatments. Fragmented patterns of REM 
sleep have been observed during the development of PTSD and within 
several years of its onset. Suvorexant is promising for maintaining overall 
sleep and REM sleep that is being disrupted by heightened arousal. In 
addition to proposing a placebo-controlled evaluation of efficacy and 
tolerability of suvorexant for TRI we further propose utilizing PSG to 
potentially elucidate physiological biomarkers of treatment response. Given 
the rising toll of trauma this proposal is a timely response to Merck’s call for 
proposals for “clinical studies exploring the investigational use of suvorexant 
in key insomnia subpopulations.” 
 
2.3 Study Design 
 
A double-blind placebo-controlled 6-week trial of suvorexant 10 – 20mg for 
trauma related insomnia (with and without PTSD) with polysomnography  
2.4 Study Flowchart 
 
 
 


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2.5 Study 
Procedures 
Participants 
 
Recruitment:  
 
We will recruit 90 adults with the expectation of retaining 70 (see power 
analysis). Participants will be between the ages of 18 to 55 with insomnia 
and trauma exposure (see below). Recruitment will occur over a 2 1/2 year 
period with the expectation of recruiting 3 per month and having 2 months for 
start-up and 6 months for final data analysis and preparing presentations and 
manuscripts. We will utilize advertisements including 10 radio and 10 
newspaper ads in the Washington Post Express at early and other strategic 
times during study recruitment. We will also continue to employ recruitment 
methods that have been successful for our program in recruiting participants 
with trauma-related symptoms including posting flyers on the Howard 
University campus and in strategic locations in the Washington DC 
community, and referrals from prior participants. Those who meet initial 
criteria by phone or on-site screening will be invited to the Clinical Research 
Unit (CRU) for further screening and informed consent. We will recruit men 
and women. This study will be open to all ethnic and racial groups; however, 
with the study location of Howard University in urban DC we anticipate that 
many of the recruited participants will be from minority groups.     
 
Screening Procedures:  
 
Participants will initially be screened over the phone with a preliminary 
checklist of inclusion and exclusion criteria as well as be further informed 
regarding the purpose and goals for the study. Those who remain interested 
and appear to meet study criteria will be invited for the screening evaluation 
at the Howard University CRU. (See study flow chart.)  
 
Inclusion criteria and justification: 
 
Physically healthy young to middle-aged adults (age 18-55) who report on 
screening and are confirmed by a clinical interview to meet the Diagnostic 
and Statistical Manual of Mental Disorders – 5th Edition (DSM-5) criteria for 
primary insomnia and Criterion A (exposure to a traumatic event) for PTSD.25 
insomnia symptoms must have started or worsened after the exposure to the 
index trauma. We anticipate that approximately half of the recruited sample 
will meet criteria for PTSD thus enabling comparisons between those with 
TRI present or absent PTSD.  
Exclusion criteria: 
 
1. Psychiatric disorders other than insomnia, PTSD and specific phobias; 
including bipolar and psychotic disorders and meeting criteria for DSM-5 
moderate alcohol or drug use disorders within the past year. 
2. Diagnosis of a sleep disorder other than insomnia including PSG findings 
of  apnea/hypopnea or periodic limb movement indices > 10/hour; 


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3. Consistent (daily) use of medication other than medications taken for 
blood pressure or nonnarcotic medications for pain and/or inflammation, 
or medical conditions that compromise sleep; 
4. Caffeine use exceeding 5 cups of coffee per day or its equivalent;  
5. Habitual bedtimes after 3AM, habitual rise times after 10AM, or habitual 
napping > 1hour/day; 
 
6. Pregnancy or breastfeeding, or expecting to conceive while in study 
(sexually active women will be required to use a medically acceptable 
form of birth control);  
7. Positive urine toxicology. 
 
Procedures 
Medication:  
After the baseline screening, participants will be randomly assigned to either 
the suvorexant or placebo group, and suvorexant or placebo will be 
administered to be taken one hour before bedtime. Randomization will be 
stratified for the presence or absence of PTSD (full or subthreshold) and 
gender. Medication will be managed by the research pharmacy and provided 
to the participant by CRU nursing staff with instructions for use. In case of a 
missed appointment they will receive a 15 day supply except for between 
treatment week 3 and week 6 when they will receive a 4 week supply. Initial 
dosing will be 10 mg. At week one, Dr. Mellman or a study clinician in 
consultation with Dr. Mellman, will determine whether to increase to 20 mg. 
based on tolerance of the medication and persistence of symptoms. If there 
are no, or only negligible, side effects and insomnia symptoms remain 
present then the dose will be increased. If tolerability is compromised by the 
dose increase the study clinician will have the option of reducing back to 10 
mg if done at or before the week 2 study visit. Dose increases can be 
deferred until week 2 but after this visit medication dose will be held constant 
until the end of the study. Participants will discontinue medication after the 
week 6 study visit. At the final follow-up 1 week later clinical assessment will 
inform the study clinician’s recommendation for further treatment including 
possible resumption or initiation of suvorexant. At each medication study the 
coordinator or research nurse will conduct a pill count and review diaries to 
determine adherence. They will also query for potential adverse events 
including a list of the most common adverse effects reported in the 
suvorexant trials22,23 will be queried as well as any events suggestive of 
parasomnias or narcolepsy phenomena (see Assessments below).   
Assessments: 
The following diagnostic and outcome assessments will be performed by 
research staff members blind to participants’ treatment condition. 


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(Diagnostic) 
Duke Structured Interview Schedule for DSM-IV-TR and International 
Classification of Sleep Disorders 2nd edition (ICSD-2) Sleep Disorder 
Diagnoses (DSISSD)26 – A widely used semi-structured interview designed 
to assess sleep disorder diagnostic status. We will use this interview to 
evaluate the presence of insomnia and to rule out insomnia that is accounted 
for by a mental disorder other than PTSD, medical conditions, and substance 
use, parasomnias, narcolepsy, and circadian rhythm sleep disorders. This 
interview will establish the onset and course of insomnia, with in conjunction 
with the information from the LEC and CAPS (see below) will determine the 
criteria for “trauma-related.” 
 
Structured Clinical Interview for DSM-V (SCID)27  The SCID is semi-
structured diagnostic interview that assesses the DSM diagnostic criteria for 
psychiatric disorders and is considered the “gold standard” for assessing 
mental disorders. A modification will be utilized in order to screen for 
excluded and establish allowable comorbid conditions.  
 
Life Event Checklist (LEC),28 is an inventory of lifetime exposure to traumatic 
events that lists 15 of the more common categories of trauma experiences 
and asks for endorsement of whether they occurred directly to the person or 
were witnessed and the age of exposure.  
 
The Clinician Administered PTSD Scale (CAPS)29 will be administered to 
further assess the details of trauma exposure, and (past week) PTSD 
severity, and lifetime diagnostic criteria. The CAPS evaluates the frequency 
and intensity of each of the 17 symptoms of PTSD and is considered a gold 
standard for assessment of the diagnosis and severity of PTSD. 
 
(Assessments used for outcomes) 
  
Insomnia Severity Index (ISI)30 The ISI is a seven-item measure used to 
evaluate insomnia severity for the past two weeks. Items are scored on a 5-
point scale and a total score is obtained by summing the seven items, with 
higher scores indicating greater insomnia severity. A cutoff score of 10 has 
been determined to be optimal for detecting insomnia in population samples. 
The ISI is also validated as an outcome measure for insomnia treatment 
studies and is widely used for that purpose.  
 
Sleep diary - Participants will complete our standard sleep diary each 
morning throughout this trial. The diary includes questions about bedtime, 
final awakening time, sleep onset latency (SOL) estimate, the number of 
awakenings, and duration of each awakening, overall sleep satisfaction, 
morning restfulness, adherence/non-adherence to the study medication 
regimen, nightmare frequency, and content of nightmare. Estimated total 
sleep time (TST) and wake after sleep onset (WASO) for each night will be 
calculated using information provided in the diary.  
 
One week CAPS nightmare item and total score minus sleep items.  
 


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Adverse Event Screening At each medication visit participants will be queried 
regarding the presence of any new symptoms or concerns. We will 
specifically query the adverse effects that occurred at a frequency that 
exceeded placebo in either the 3 month pivotal trials22 or the 1-year study23 
including somnolence, fatigue, dry mouth, dyspepsia, and peripheral edema. 
We will also specifically query the pre-specified events of interest for those 
trials including suicidal ideation, complex sleep-related behaviors (e.g. 
getting food during the night and not remembering it), sleep onset or off-set 
hallucinations, sleep paralysis, and falls. Excessive daytime sleepiness will 
be assessed by administering the Epworth Sleepiness Questionnaire.31 
Weight and vital signs will be obtained at each study visit. At the post-
treatment visit specific inquiry will also include the occurrence of common 
medication withdrawal symptoms such as dizziness, shaking, nausea, and 
muscle tension as well as re-assessment of insomnia and sleep patterns for 
that period.   
 
Polysomnography (PSG):  
 
PSG collection includes a standard electroencephalogram (EEG) montage 
with two central, frontal, and occipital leads, two electrooculograms, chin and 
limb electromyograms, and an electrocardiogram (ECG). Recordings will be 
conducted using an Embla (Denver, CO) Titanium unit in the CRU. 
Screening for sleep disordered breathing and limb movements will be 
performed using the screening night data. Visual scoring of sleep records 
from a computer monitor will be done following the American Academy of 
Sleep Medicine (AASM) Manual, Version 2.0.32 The REMLogic software 
(Embla) will calculate sleep parameters including TST, SOL, WASO, the 
percentage of each sleep stage, and mean duration of continuous REM 
segment. Calculation of REM segment length used our previous criteria16 of 
at least two epochs of consecutive REM sleep with no more than one 30-sec 
epoch of non-REM sleep interruption. The sleep parameters for baseline will 
be obtained from the second night recording after an accommodation 
recording that will also screen for apnea will be used in data analysis. 
Respiratory strain gauge, nasal air flow, and oximetry monitors will be 
included on the first but not subsequent nights. Participants will be instructed 
to go to bed near their habitual bedtimes and will wake up naturalistically. 
PSG will be done prior to medication and after 3 weeks of medication 
treatment to allow for stable dosing.   
 
Summary of changes (9/17/2018)  
1. Allowing ongoing use of medications for blood pressure and non-narcotic 
medications for pain and/or inflammation.  
Pg 2, exclusion criteria #3 of consent  
Pg 7, first line also #3 in protocol  
 
2. No longer restricting the time from the trauma and onset of symptoms  
Pg 6 of the protocol  
 
 
 


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2.6 Study Duration 
Three years – 2 months preparation, 30 months to recruit 3 participants per 
month except December, 4 months for final data analyses, presentation and 
manuscript preparation Estimate the length of time (e.g., number of days, 
weeks, months) required to recruit patients and complete the study. 
2.7 Statistical 
Analysis and 
Sample Size 
Justification  
The data will be analyzed by the Investigator and Co-investigator. 
Main outcomes will be ISI, CAPS nightmare frequency and total score, diary 
and PSG sleep latency and WASO at week 3 and for non-PSG variables 
Med week 6. We will also explore effects on REM and SWS and their 
relationships to other study outcomes. 
 
An alpha level of .05 (one-tailed) will be applied in testing Hypotheses 2a), 
2b), 2d), and 2e). Initially, data will be pre-screened for errors, outliers, 
normality of distributions, and any necessary modifications, such as 
transformation of variables and/or elimination of cases, will be conducted.  
 
Our initial objectives are descriptive. We will generate frequencies of types of 
trauma exposures associated with insomnia and the rates for PTSD 
diagnoses and sub-diagnostic threshold PTSD symptoms in the recruited 
study population (Objective 1) and the frequency of adverse events 
(Objective 2). The latter will be descriptively contrasted to the extant data for 
suvorexant from the insomnia registry trials as a guide to planning future 
trials including dosing.  
 Hypothesis 2a) Insomnia will improve, and nightmares and 
other PTSD symptoms will be reduced with suvorexant treatment 
compared with placebo: We will compare baseline characteristics of the 
treatment groups using independent samples t-tests for continuous variables 
or chi-square tests for categorical variables. If a significant group difference 
is found in some of the variables, the variable(s) will be included in 
subsequent analyses as a covariate(s). We will perform 2 (Group) x 3 (Time: 
baseline, Med week 3, and week 6) mixed ANOVAs or ANCOVAs [if there is 
a covariate(s)] to compare the changes in ISI scores, nightmare frequency, 
and CAPS scores, separately, between the two groups. 
 
Hypothesis 2b) Improved sleep will be associated with reduced 
non-sleep PTSD symptoms: Correlation coefficients between baseline – 
Med week 6 changes in sleep measures (e.g., ISI scores and nightmare 
frequency) and changes in the CAPS scores excluding two sleep-related 
items will be computed. In addition, we will exploratively examine if there is 
an interaction with treatment condition by performing regression analyses in 
which CAPS scores will be predicted by changes in sleep measures, 
treatment condition, and a Sleep measure X Treatment condition interaction.  
Hypothesis 2d) Sleep latency and wake after sleep onset (WASO) 
will be reduced with suvorexant treatment compared with placebo:: We 
will perform 2 (Group: suvorexant vs. placebo) x 2 (Time: Baseline and Med 
week 3) mixed ANOVAs or ANCOVAs [if there is a covariate(s)] to compare 
the changes in PSG measured sleep latency and WASO between the 
suvorexant and placebo groups. 
 
           Exploratory hypothesis 2e) When reduced at baseline (i.e., SWS 
below 100 minutes and mean REM segment duration below 15 


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minutes), SWS and the duration of continuous segments of REM sleep 
will increase with suvorexant than placebo: Participants with reduced 
baseline SWS (below vs. above 100 minutes) and mean REM segment 
duration (below vs. above 15 minutes) will be included in the analyses. 2 
(Group) x 2 (Time: Baseline and Med week 3) mixed ANOVAs or ANCOVAs 
will be performed to compare treatment changes in SWS and REM segment 
duration between the suvorexant and placebo groups.  
 
Power Considerations:  
 
G*Power 3.1 33 was used to conduct power analysis.  
Power analysis for Hypothesis 2a) is based on the effect size 
estimated using findings of Herring and colleagues’22 placebo controlled trial 
of suvorexant in adults with insomnia. Since there are no data for 
suvorexant on trauma related nightmares and PTSD symptoms, we also 
used Taylor and colleagues’24 placebo controlled trial of prazosin in civilian 
outpatients with PTSD, sleep disturbances, and nightmares. Taylor et al. 
found a large-size effect of prazosin on changes in trauma-related nightmare 
severity compared with placebo (d = 0.96 or f = 0.48) and PTSD severity (d 
=0.79 or f = 0.40) and a medium-size effect on changes in trauma-related 
insomnia symptoms severity (d = 0.50 or f = .25). Herring and colleagues 
found a small-size effect of a 1-month suvorexant treatment (20mg for 
nonelderly and 15mg for elderly) on insomnia severity measured by the ISI (d 
= 0.39 or f = 0.20). To detect an f = 0.20 Group x Time interaction effect in 
the proposed mixed ANOVA with 80% power, a total of 42 participants are 
needed.   
Power analysis for Hypothesis 2b) is based on the effect sizes 
estimated using Krakow and colleagues’ findings34 from their study 
examining effects of cognitive behavioral therapy for nightmares and 
insomnia in crime victims with PTSD. They found correlations between 
changes in nightmare frequency, insomnia severity, and sleep quality and 
changes in overall PTSD symptom severity ranging from r = .37 to .40. A 
sample size of 43 will allow for detecting similar size effects with 80% power. 
  
Power analysis for Hypothesis 2d) is based on findings from the 
aforementioned Herring and colleagues’ study. They found that effects of 
suvorexant on sleep latency and WASO were f =0.17 and 0.31, respectively. 
To detect an effect size of 0.17 using the proposed mixed ANOVA with 80% 
power, a total of 70 participants are needed.  
 
Power analysis for Exploratory hypothesis 2e) is based on findings from 
the aforementioned Taylor and colleagues’ study. They found that the effect 
of prazosin on mean REM period duration was f = 0.50. Using the proposed 
mixed ANOVA, a total of 16 participants will allow for detecting a large size 
within-between interaction effect (f = 0.50) with 80% power.   
 
2.8 Specific Drug 
Supply 
Requirements  
The study will require suvorexant 10 and 20 mg and placebo 10 and 20 mg in 
coded pill containers. It will be stored and managed by the Howard University 
Hospital Research Pharmacy.  


      MISP Template: Protocol 
12 
Final Version: 8/13/2010 
2.9 Adverse 
Experience 
Reporting 
We will use the methods specified in the protocol and will adhere to the 
Model Study Agreement.  
2.10 Itemized Study 
Budget  
Budget on Merck Template is included.   
2.11 References 
1. Green BL. Disasters and posttraumatic stress disorder. In: Davidson JRT, 
Foa EB, eds. Posttraumatic stress disorder: DSM-IV and beyond. 
Washington, DC: American Psychiatric; 1993:75-98. 
2. Seelig AD, Jacobson IG, Smith B, et al. Sleep patterns before, during, and 
after deployment to Iraq and Afghanistan. Sleep. 2010;33(12):1615-1622. 
3. Krakow B, Haynes PL, Warner TD, et al. Nightmares, insomnia, and sleep-
disordered breathing in fire evacuees seeking treatment for posttraumatic 
sleep disturbance. J Trauma Stress. 2004;17(3):257-268. 
4. Neylan TC, Marmar CR, Metzler TJ, et al. Sleep disturbances in the 
Vietnam generation: Findings from a nationally representative sample of 
male Vietnam veterans. Am J Psychiatry. 1998;155(7):929-933. 
5. Ohayon MM, Shapiro CM. Sleep disturbances and psychiatric disorders 
associated with posttraumatic stress disorder in the general population. 
Compr Psychiatry. 2000;41(6):469-478. 
6. Leskin GA, Woodward SH, Young HE, Sheikh JI. Effects of comorbid 
diagnoses on sleep disturbance in PTSD. J Psychiatr Res. 2002;36(6):449-
452. 
7. Morin CM, Belleville G, Bélanger L, Ivers H. The insomnia severity index: 
Psychometric indicators to detect insomnia cases and evaluate treatment 
response. Sleep. 2011;34(5):601-608. 
8. Mellman TA, Hall Brown TS, Kobayashi I, et al. Blood pressure dipping 
and urban stressors in young adult African Americans. Ann Behav Med. in 
press. 
9. Zayfert C, DeViva JC. Residual insomnia following cognitive behavioral 
therapy for PTSD. J Trauma Stress. 2004;17(1):69-73. 
10. Mellman TA, Clark RE, Peacock WJ. Prescribing patterns for patients 
with posttraumatic stress disorder. Psychiatr Serv. 2003;54(12):1618-1621. 
11. Kobayashi I, Boarts JM, Delahanty DL. Polysomnographically measured 
sleep abnormalities in PTSD: A meta-analytic review. Psychophysiology. 


      MISP Template: Protocol 
13 
Final Version: 8/13/2010 
2007;44(4):660-669. 
12. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the 
hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146(6):697-
707. 
13. Foulkes WD. Dream reports from different stages of sleep. J Abnorm 
Psychol. 1962;65(1):14-25. 
14. Fosse MJ, Fosse R, Hobson JA, Stickgold RJ. Dreaming and episodic 
memory: A functional dissociation? J Cogn Neurosci. 2003;15(1):1-9. 
15. Walker MP, van der Helm E. Overnight therapy? the role of sleep in 
emotional brain processing. Psychol Bull. 2009;135(5):731-748. 
16. Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B. REM sleep 
and the early development of posttraumatic stress disorder. Am J Psychiatry. 
2002;159(10):1696-1701. 
17. Schlosberg A, Benjamin M. Sleep patterns in three acute combat fatigue 
cases. J Clin Psychiatry. 1978;39(6):546-549. 
18. Mellman TA, Kulick-Bell R, Ashlock LE, Nolan B. Sleep events among 
veterans with combat-related posttraumatic stress disorder. Am J Psychiatry. 
1995;152(1):110-115. 
19. Woodward SH, Arsenault NJ, Michel GE, Santerre CS, Groves WK, 
Stewart WK. Polysomnographic characteristics of trauma-related nightmares. 
Sleep. 2000;23(S2):A356-A357. 
20. Mellman TA, Kobayashi I, Lavela J, Wilson B,Wilson, Hall Brown TS. A 
relationship between REM sleep measures and the duration of posttraumatic 
stress disorder in a young adult urban minority population. Sleep. 
2014;37:1321-1326. 
21. Kilduff TS, Peyron C. The hypocretin/orexin ligand–receptor system: 
Implications for sleep and sleep disorders. Trends Neurosci. 2000;23(8):359-
365. 
22. Herring WJ, Connor KM, Ivgy-May N, et al. Suvorexant in patients with 
insomnia: Results from two 3-month randomized controlled clinical trials. Biol 
Psychiatry. in press. 
23. Michelson D, Snyder E, Paradis E, et al. Safety and efficacy of 
suvorexant during 1-year treatment of insomnia with subsequent abrupt 
treatment discontinuation: A phase 3 randomized, double-blind, placebo-
controlled trial. Lancet Neurol. 2014;13(5):461-471. 
24. Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective 
sleep measures and clinical symptoms in civilian trauma posttraumatic stress 


      MISP Template: Protocol 
14 
Final Version: 8/13/2010 
disorder: A placebo-controlled study. Biol Psychiatry. 2008;63(6):629-632. 
25. American Psychiatric Association. Diagnostic and statistical manual of 
mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 
2013. 
26. Edinger JD, Wyatt JK, Olsen MK, et al. Reliability and validity of insomnia 
diagnoses derived from the duke structured interview for sleep disorders. 
Sleep. 2009;32(suppl):A265. 
27. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical 
interview for DSM-IV-TR axis I disorders, research version, patient edition. 
New York: Biometrics Research; 2002. 
28. Gray MJ, Litz BT, Hsu JL, Lombardo TW. Psychometric properties of the 
life events checklist. Assessment. 2004;11(4):330-341. 
29. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney 
DS. The development of a clinician-administered PTSD scale. J Trauma 
Stress. 1995;8(1):75-90. 
30. Bastien CH, Vallières A, Morin CM. Validation of the insomnia severity 
index as an outcome measure for insomnia research. Sleep Med. 
2001;2(4):297-307. 
31. Johns MW. A new method for measuring daytime sleepiness: The 
Epworth Sleepiness Scale. Sleep. 1991;14(6):540-545. 
32. American Academy of Sleep Medicine. The AASM manual for the scoring 
of sleep and associated events: Rules, terminology and technical 
specifications version 2.0. American Academy of Sleep Medicine; 2012. 
33. Faul F, Erdfelder E, Buchner A, Lang A. Statistical power analyses using 
G* power 3.1: Tests for correlation and regression analyses. Behav Res 
Methods. 2009;41(4):1149-1160. 
34. Krakow B, Johnston L, Melendrez D, et al. An open-label trial of 
evidence-based cognitive behavior therapy for nightmares and insomnia in 
crime victims with PTSD. Am J Psychiatry. 2001;158(12):2043-2047. 
  
2.12 Publication 
Plan 
We plan to submit at least 2 manuscripts close to the end of the funding 
period to SLEEP and Journal of Traumatic Stress.  
2.13 Curriculum 
Vitae 
 
Included  
 
 
 
 

ICF_001.pdf: 
Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
 
Informed Consent for Clinical Research 
Georgetown-Howard Universities Center for Clinical and Translational Science 
(GHUCCTS) 
INSTITUTION:                           HOWARD UNIVERSITY 
 
INTRODUCTION 
 
You are invited to consider participating in this study. The study is called Suvorexant and Trauma-related 
Insomnia (A placebo controlled trial with polysomnography). 
Please take your time to make your decision. Consider discussing it with your family and friends. It is important 
that you read and understand several general principles that apply to all who take part in our studies: 
 
(a) Taking part in the study is entirely voluntary; 
 
(b) Personal benefit to you may or may not result from taking part in the study, but knowledge may be 
gained from your participation that will benefit others; 
 
(c) You may decline to participate or you may withdraw from the study at any time without loss of any 
benefits to which you are entitled and without jeopardizing your access to care, treatment and health 
services unrelated to the research. 
 
The purpose and nature of the study, possible benefits, risks, and discomforts, other options, your rights as a 
participant, and other information about the study are discussed below. Any new information discovered, at any 
time during the research, which might affect your decision to participate or remain in the study will be provided 
to you. You are urged to ask any questions you have about this study with the staff members who explain it to 
you. You are urged to take whatever time you need to discuss the study with your physician, hospital personnel 
and your family and friends.  The decision to participate or not is yours.  If you decide to participate, please sign 
and date where indicated at the end of this form.  The investigator (person in charge of this research study) is 
Dr. Thomas Mellman.  
 
The research is being sponsored by Merck & Co. Merck & Co. is called the sponsor and up to $523,000 is being 
paid to Howard University to conduct this study with Thomas Mellman as the primary investigator. Merck is 
also the maker of the drug being evaluated in this study. Dr. Mellman occasionally serves as a paid consultant to 
Merck.  
 
WHY IS THE STUDY BEING DONE?  
 
You are being asked to participate in this study because Dr. Mellman and his staff aim to investigate the 
effectiveness of suvorexant for trauma-related insomnia. Sleep problems are common among those with 
exposure to trauma and can contribute to other mental and physical problems. Medications and other treatments  


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
aimed at reducing PTSD have not been very effective for helping insomnia. Suvorexant was recently approved 
by the Federal Drug Administration for the treatment of insomnia but it has not been evaluated for treating 
insomnia related to trauma. It works in a way that is different from other available medications for insomnia.   
 
You may not participate in this study if any of the following apply to you: 
 
1. Severe psychiatric disorders (not including insomnia, PTSD and specific phobias) such as bipolar and 
psychotic disorders, and moderately severe alcohol or drug use disorders within the past year. 
2. Certain sleep disorders other than insomnia including sleep recording findings indicating sleep apnea.  
3. Consistent (daily) use of medication other than medications taken for blood pressure or nonnarcotic 
medications for pain and/or inflammation, or medical conditions that compromise sleep; 
4. History of moderate to severe traumatic brain injury or mild traumatic brain injury with ongoing post-
concussive symptoms;  
5. Having or having had a plan or the intention to commit suicide in the past 6 months or a concerning history 
of prior suicidal behavior;   
6. Caffeine use exceeding 5 cups of coffee per day;  
7. Regular bedtimes after 3AM, rise times after 10AM, or napping > 1hour/day; 
8. Pregnancy or breastfeeding, or expecting to conceive while in the study;  
9. Positive urine test for drugs. 
 
The purpose of this study is to find out what effects (good and bad) suvorexant has on you and your trauma-
related insomnia.  
 
This research is being done because standard treatments have not worked well for insomnia with posttraumatic 
stress disorder and medication indicated for treating insomnia has not focused specifically on people whose 
sleep problems are related to trauma.  
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
Participants in the study are referred to as subjects. 
 
About 105 subjects will take part in this study and all will be recruited at this site. 
 
 
 
WHAT IS INVOLVED IN THE STUDY? 
 
Interviews and questionnaires: involve answering questions asked by a member of the research team or filling 
out forms. These will include questions about traumatic experiences, your sleep patterns, symptoms related to 
stress and depression, and your personal and medical history. These questionnaires and interviews will vary in 
their time to complete, depending on which are required for that particular visit (typically one hour and no 
longer than two hours).  
 
Sleep recording (polysomnography): The recordings require you to sleep over night in Howard University’s 
Clinical Research Unit on three different nights (two before and one during medication treatment). Monitors 
will be attached to your scalp and face by tape or removable adhesive, and your chest on the first night. You 
will be asked to go to bed at your normal bed time and then wake up naturally in the morning.  


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
 
Suvorexant and Placebo Treatment: You will take your medication 30 minutes before bed every night of the 
six-week investigation. You will have the opportunity to express your comments and concerns about the 
medication each week (with the opportunity to change your dosage during the first 2 weeks if indicated). You 
will be asked to discontinue medication after 6 weeks, and then complete a follow-up 1 week after stopping. A 
study clinician will discuss options for further treatment with you at this time.  
 
You will be randomly assigned (like flipping a coin) into one of 2 study groups: to take either suvorexant (the 
active medication) or placebo (like a sugar pill) 30 minutes before going to bed. There is a 50% chance of 
receiving either of these treatments. The initial dose will be 10mg, after an evaluation an increase to 20 mg may 
be recommended. Neither you nor the researchers will choose or know what group you will be in. You will 
have an equal chance of being placed in either group. You will be given a study medication and it will either 
contain Suvorexant or placebo (pills with no medicine). 
 
Standard procedures being done because you are in this study. 
 
❖ All participants from both study groups will be asked to fill out questionnaires and answer questions 
about sleep, symptoms related to stress, mental health, personal and medical history in the Howard 
University Clinical Research Unit. Assessment procedures include the following:  
 
1. Demographic and Health Questionnaire- includes questions about your gender, race/ethnicity, 
income, health and education. (Estimated completion time: 3 minutes)  
 
2. Physical Examination – includes measurement of vital signs and height and weight, and a brief 
physical exam conducted by a physician or a nurse practitioner. 
 
3. Urine toxicology screening – measuring whether there is alcohol or drugs in your urine. 
 
4. Urine pregnancy test (women only) – examining whether you are pregnant through your urine sample. 
Because the study involves medication, you will be required to avoid pregnancy while you are 
participating in the study.  
 
5. Duke Structured Interview Schedule for DSM-5 Sleep Disorders (DSISD) – Interview assessing 
types of sleep disorders (30 minutes) 
 
6. Structured Clinical Interview for DSM-5 (SCID-5) – Interview about mental health symptoms and 
disorders. (45 minutes) 
 
7. Life Event Checklist (LEC) – A survey of exposure to specific traumatic events (5 minutes) 
 
8. The Clinician Administered PTSD Scale (CAPS) – interview about the presence and severity of 
symptoms related to traumatic stress (30 minutes, screening, and week 1, 3, 6) 
 
9. The Columbia-Suicide Severity Rating Scale (C-SSRS) – A questionnaire that evaluates whether a 
person is having suicidal thoughts and behaviors (10 minutes, each visit (screening, baseline, week 1, 2, 
3, 6, follow up) 
 


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
10. Insomnia Severity Index (ISI) – A self-report measure that assesses the severity of insomnia 
symptoms.  (2 minutes) 
 
11. Sleep Diaries - A diary that is filled out in the morning to report how you slept during the night. (2 
minutes every morning over week 1 and 2, 3,6, and follow up) 
 
12. Polysomnography (PSG) – You will be monitored overnight in the Howard University Clinical 
Research Unit with several small electrode sensors that are placed on the scalp, chin, and over the heart 
which measure brain and heart activity during sleep. Other monitors measure breathing and will be 
included on the first night but not the second or third recording. If eligible you will be asked to 
participate in three overnight sleep recordings.  
 
Please advise the researchers of any medications you are taking.  In addition, if you are taking any over-the-
counter drugs or herbal supplements which you have obtained from the drug store, grocery store, etc., you 
should advise the researchers. 
 
HOW LONG WILL I BE IN THE STUDY? 
 
You will take the study medication for 6 weeks unless you or a study clinician choose for you to withdraw. The 
study clinician may decide to take you off this study if it is in your medical best interest, your condition 
worsens, or new information about the drug becomes available. You will be asked to discontinue medication 
after 6 weeks, and then complete a follow-up 1 week after stopping. A study clinician will discuss options for 
further treatment with you at this time.  
 
You can stop participating at any time.  However, if you decide to stop participating in the study, we encourage 
you to talk to the researcher and your regular doctor first. 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
Risks and side effects related to the (procedures, drugs, or devices) we are studying include: 
 
In prior studies, the most common side effect reported was feeling tired or drowsy during the day. This risk was 
more common with suvorexant than placebo (7 percent versus 3 percent). Because of this you should be 
cautious about driving when you first take the medication.  
 
Less likely side effects (less than one percent in prior studies) that could occur include:   
• temporary inability to move or talk (sleep paralysis) for up to several minutes while you are going to sleep 
or waking up  
• temporary weakness in your legs that can happen during the day or at night. 
• “sleep-walking” or doing other activities when you are asleep like eating, talking, having sex, or driving a 
car. 
Avoidance of Pregnancy: The medicines and procedures used in this study may be unsafe for an unborn baby, 
an infant, sperm, and eggs. If you, as a subject of study, are a woman of child bearing potential, you must agree 
to avoid pregnancy during your participation in this study. If you do become pregnant during the study, you 
should immediately notify Dr. Mellman at 202-806-7818/202-865-6100 (after hours). In addition, if you are 
already pregnant or are breast feeding, you cannot participate in this study. 
 


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
There may also be side effects, other than those listed that we cannot predict. Many side effects go away shortly 
after the (drug /intervention) is stopped, but in some cases side effects can be serious, long lasting or permanent. 
For more information about risks and side effects contact the investigator at 202-806-7818 
 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
 
If you agree to take part in this study, there may or may not be direct medical benefit to you. Probable benefits 
may include falling asleep faster and staying asleep longer.  
 
We cannot promise that you will experience medical benefits from participating in this study.  We hope the 
information learned from this study will benefit others in the future. 
 
WHAT OTHER OPTIONS ARE THERE? 
 
Whether you participate in this study or not, you will receive care to manage your symptoms and keep you 
comfortable. Instead of being in this study, you have these options: 
• Prazosin, studies suggest that this is can reduce nightmares in posttraumatic stress disorder. 
• Cognitive behavioral therapy has been effective for treating insomnia. 
• A number of medications such as Ambien are used for insomnia but are not established for trauma-
related insomnia.   
 
WHAT ABOUT CONFIDENTIALITY? 
 
Efforts will be made to protect your medical records and other personal information to the extent allowed by 
law. However, we cannot guarantee absolute confidentiality.  Medical records of research study participants are 
stored and kept according to legal requirements. You will not be identified in any reports or publications 
resulting from this study. In addition to the researchers and research institution(s) conducting this study, 
organizations that may request to inspect and/or copy your research and medical records for quality assurance, 
data analysis and other research related and operational or administrative purposes, include groups such as: 
 
Merck & Co., Food and Drug Administration, GHUCCTS Institutional Review Board (IRB), and Howard 
University. 
 
Please note that administrative personnel involved in processing your payment for participation will be aware of 
your identity. 
 
CLINICALTRIALS.GOV 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.  
This Web site will not include information that can identify you.  At most, the Web site will include a summary 
of the results.  You can search this Web site at any time. 
 


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
DATA SECURITY 
 
If information about your participation in this study is stored in a computer, we will take the following 
precautions to protect it from unauthorized disclosure, tampering, or damage: 
The principal investigator will be responsible for data management and maintaining confidentiality. Subject 
confidentiality will be protected to the full extent required by law and applicable local, State and Federal 
regulations and guidelines, including HIPAA. All patients will be assigned study numbers to replace specific 
identifying information. All data will be compiled in electronic form.  Throughout the process of creating the 
database the integrity and security of the data will be monitored by the principal investigator and will occur on a 
weekly basis.  All electronic data will be stored on secure, password-protected computers and drives and only 
authorized personnel will have access to the data. The principal investigator will oversee and monitor all aspects 
of the study.   
 
WHAT ARE THE COSTS? 
 
Study subjects will not have to pay for the study drug/treatment.  There is no additional cost to you or your 
insurance company in relation to this study. 
 
You or your insurance company will be charged for continuing medical care and/or hospitalization that are not a 
part of the study. You may find a National Cancer Institute guide: “Clinical Trials and Insurance Coverage – a 
Resource Guide” helpful. You may ask your doctor for a copy, or it is available on the world wide web at 
http://cancer.gov/clinicaltrials/insurance. 
 
POLICY/PROCEDURES FOR RESEARCH RELATED INJURY 
 
The Policy and Procedure of Merck & Co. are as follows:  
The sponsor will not pay for care necessitated by a research related injury 
 
The Policy and Procedure of Howard University is as follows:  
If you are injured as a result of the research procedures, emergency medical care will be provided; however, 
financial compensation will not be available. Howard University Hospital may provide short-term and long-
term medical care for any injury resulting from your participation in research here. However, if you are for 
some reason denied medical care, you have the right to pursue legal representation to help you gain medical 
care for your injury.  
 
PAYMENT FOR PARTICIPATION 
 
There is no cost to participants in this research study. You will receive payments to offset 
the time, inconvenience and transportation needs of study participation: $50 for the first visit, $25 for the other 
visits and $125 for each overnight sleep recording. 
 
You should not expect anyone to pay you for pain, worry, lost income, or non-medical care costs that occur 
from taking part in this research study. 
 


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
 
Taking part in this study is voluntary. You may choose not to take part in or leave the study at any time. If you 
choose to not take part in or to leave the study, your regular care will not be affected nor will your relations with 
your physicians, other personnel and the hospital or university.  In addition, you will not lose any of the benefits 
to which you are entitled. 
 
We will tell you about new information that may affect your health, welfare, or participation in this study. 
 
By signing this form, you do not lose any of your legal rights. 
 
NEW FINDINGS 
 
Throughout the study, we will tell you if there is new information we receive about treatments that may be 
appropriate for you, about the experimental treatments under investigation in this study, and any information 
that may affect your interest in remaining in the study.  
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about the study or a research-related injury, any problems, unexpected physical or psychological 
discomforts, or if you think that something unusual or unexpected is happening, call Dr. Thomas Mellman at 
(202) 806-7818 or after hours through the page operator at (202) 865-6100. Be sure to inform your physician of 
your participation in this study. 
 
For questions about your rights as a research participant, contact the GHUCCTS Institutional Review Board at: 
 
 
Address: 
Georgetown University Medical Center 
 
 
Telephone: (202) 687-1506 
 
 
 
3900 Reservoir Road, N.W. 
 
 
 
SW104 Med-Dent 
 
 
 
Washington, D.C.  20057 
 
Withdrawal by investigator, physician, or sponsor 
 
The investigators, physicians or sponsors may stop the study or take you out of the study at any time should 
they judge that it is in your best interest to do so, if you experience a study-related injury, if you need additional 
or different medication, or if you do not comply with the study plan. They may remove you from the study for 
various other administrative and medical reasons. They can do this without your consent. 
 
MAKING YOUR CHOICE 
 
Please read the sentence below and think about your choice. Please circle “Yes” or “No” then add your 
initials and date after you answer. No matter what you decide to do, it will not affect your care. If you 
have any questions, pleas talk to your study doctor or nurse, or call the Institutional Review Board at 
202-687-1506 
 


Principal Investigator: Dr. Thomas Mellman, MD.  
  
Study Number: 2015-1333 
Title: Suvorexant and Trauma–related Insomnia (A placebo controlled trial with polysomnography)       
 
Version Date: 12/09/2019 
 
RESEARCHER’S STATEMENT 
 
I have fully explained this study to the subject.  As a representative of this study, I have explained the purpose, the 
procedures, the benefits and risks that are involved in this research study. Any questions that have been raised have been 
answered to the individual’s satisfaction. 
 
 
_________________________________ 
 
_________________  
 
_______ 
Signature of person obtaining the consent 
 
Print Name of Person  
 
Date 
 
I, the undersigned, have been informed about this study’s purpose, procedures, possible benefits and risks, and I have 
received a copy of this consent. I have been given the opportunity to ask questions before I sign, and I have been told that 
I can ask other questions at any time. I voluntarily agree to participate in this study. I am free to withdraw from the study 
at any time without need to justify my decision. This withdrawal will not in any way affect my future treatment or medical 
management and I will not lose any benefits to which I am otherwise entitled. I agree to cooperate with Dr. Thomas 
Mellman and the research staff and to inform them immediately if I experience any unexpected or unusual symptoms. 
 
 
_________________________________ 
 
_________________  
 
_______ 
Signature of Subject  
 
 
 
Print Name of Subject 
 
Date