Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance in Posttraumatic Stress
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-75
SponsorVA Office of Research and Development
About this trial
Post-traumatic stress disorder (PTSD) is a common consequence of combat that can result in trauma-related hyperarousal and sleep disturbances. Poor sleep, one of the most common complaints in Veterans with PTSD, can be distressing, impair concentration and memory, and contribute to physical health conditions, such as metabolic syndrome, inflammation, and cardiovascular disease. The orexin neuropeptide system underlies both sleep and stress reactivity. Suvorexant, a drug that reduces orexin, improves sleep in civilians, but has not yet been tested in Veterans with PTSD. This study will test whether suvorexant can improve sleep disturbances and PTSD symptoms in Veterans. Suvorexant may benefit Veterans by improving sleep quickly while also reducing PTSD symptoms over the long term, and with fewer side effects that were common in previous medications used to treat these conditions. Improving Veterans' sleep and PTSD symptoms could lead to better emotional and physical well-being, quality of life, relationships, and functioning.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Men and Women, age range of 18 to 75, with a history of US military service, capable of reading and understanding English, and able to provide written informed consent
Criterion A event meets DSM-5 criteria
PTSD symptoms >3 months duration as indexed by a CAPS-5 12 and a partial PTSD diagnosis at screening
Insomnia indicated by an ISI score > 14
Disqualifiers
DSM-5 alcohol, marijuana, and/or other drug use disorder in the last 3 months
Mild alcohol use not meeting criteria for moderate or severe use disorder may be allowed on a case-by-case basis
Mild or moderate marijuana use disorder may be allowed on a on a case-by-case basis
Manic or psychotic episode in the last 5 years
Trial design
Design model
Parallel
Treatments tested in this trial
Suvorexant
DrugSuvorexant, a dual orexin receptor antagonist, is the first in a new class of drugs with great promise of addressing insomnia in Veterans with PTSD. Suvorexant targets the orexin neuropeptide system and has been shown to be highly successful in treating insomnia.
Placebo
Other interventionVisibly matched, equally weighted placebo tablets. In addition to matching in appearance and weight, they will have identical packaging and labeling as randomized, blinded study medication.
Treatment groups
190 Participants
are divided into 2 treatment groupsGroup A: SuvorexantExperimental treatment 1 intervention
Group B: Identical PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Insomnia Severity Index (ISI)
The ISI is a specific index of perceived insomnia severity. Areas assessed include problems with sleep onset, sleep maintenance, and early morning awakening; dissatisfaction with sleep; interference with daily functioning; impact on quality of life; and worry about sleep problems.
Time frame
Change from baseline to week 122
Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is a 30-item interview that is the gold standard assessment for PTSD. The CAPS-5 provides a dimensional and categorical measure of PTSD, and incorporates frequency and intensity of symptoms into a single severity score. The CAPS-5 will determine a threshold for PTSD severity (past week) at baseline (excluding change in item #20 falling and staying asleep). Possible scores range from 0 to 80. All trained and certified CAPS-raters will function independently and will not be involved in recruitment, study coordination, or evaluation of side effects.
Time frame
Change from baseline to week 12Secondary outcomes
1
Wrist Actigraphy
Sleep wake schedule will be monitored with wrist actigraphy (Micro Motionlogger, Ambulatory Monitoring, Inc.). The actigraph provides continuous activity data using a battery-operated wristwatch-size microprocessor that senses motion with a three axis accelerometer. High-resolution data will be down-sampled to one-minute sample intervals for conventional actigraphic sleep-wake estimation and analyzed using ActionW-2 (Ambulatory Monitoring, Inc.) software. Sleep efficiency, sleep maintenance, total sleep time and wake after sleep onset will be used as secondary measures of sleep.
Time frame
Change from 1 week at baseline, and weeks 4, 8, and 122
Pittsburgh Sleep Quality Index-PTSD Addendum (PSQI-A)
PSQI-A will be used to assess disruptive nocturnal behaviors related to PTSD, including nightmares, hot flashes and episodes of terror during sleep. Scores ranges from 0 (normal) to 21 (severe). The investigators plan to evaluate nightmares as a secondary outcome.
Time frame
Change in PTSD-related nightmares across the 12 week trialOther outcomes
1
Clinical Global Impression (CGI)
The Clinician and patient reports of improvement on the CGI (depression, mood, vigor, suicidality, daytime somnolence, and functional disability rating scales.) The CGI measures psychiatric treatment response by evaluating global severity of illness and change in the clinical condition over time. It consists of 3 global subscales: Severity of Illness, Global Improvement, and Efficacy Index. Item 1 is rated on a seven-point scale (1=normal to 7=extremely ill); item 2 on a seven-point scale (1=very much improved to 7=very much worse); and item 3 on a four-point scale (from 'none' to 'outweighs therapeutic effect'). The CGI will be used as a secondary measure of remission (i.e., CGI-I of 1 "very much improved" or 2 "much improved").
Time frame
Change across the 12 week trialSponsors and contacts
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Source ClinicalTrials.gov