Sleep Initiation and Maintenance DisordersPhase 4NCT03642028
Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance in Posttraumatic Stress
A Phase 4 study testing Suvorexant in people with Sleep Initiation and Maintenance Disorders and Stress Disorders, Posttraumatic, run by VA Office of Research and Development at 4 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sleep Initiation and Maintenance Disorders, Stress Disorders, Posttraumatic
- What is being tested?
- Suvorexant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 145 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Aug 2019to 30 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women 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
- Post-traumatic stress disorder (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
- Subjects on non-exclusionary medications must be on a stable dose for at least 4 weeks prior to randomization, which includes the Selective Serotonin Reuptake Inhibitors (SSRIs) e.g.:
- Sertraline
Show all 25Show fewer
- Paroxetine
- Fluoxetine
- Fluvoxamine
- Citalopram
- Escitalopram
- Serotonin-norepinephrine reuptake inhibitors (SNRIs), e.g.:
- Desvenlafaxine
- Duloxetine
- Levomilnacipran
- Venlafaxine
- For subjects who are in psychotherapy, treatment must be stable for 6 weeks
- Women of child-bearing potential must not be pregnant or have plans for pregnancy or breastfeeding during the study and must use a medically acceptable method of birth control, e.g.:
- oral
- implantable
- injectable
- transdermal contraceptive
- intrauterine device
- double-barrier method
- Sleep apnea score <30; if screening indicates mild or moderate sleep apnea (score between 5 and 30), referral will be provided
Who cannot join
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (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
- Exposure to trauma in the last 3 months
- Prominent suicidal or homicidal ideation or any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS) or increased risk of suicide that necessitates additional therapy or inpatient treatment
Show all 30Show fewer
- Pre-existing severe sleep apnea (score >30) in the absence of adherence to effective treatment (such as CPAP or oral device) or positive screen for severe sleep apnea by type III device (score > 30)
- Neurologic disorder or systemic illness affecting CNS function
- Chronic or unstable medical illness including:
- unstable angina
- myocardial infarction within the past 6 months
- congestive heart failure
- preexisting hypotension or orthostatic hypotension
- heart block or arrhythmia
- chronic renal or hepatic failure
- pancreatitis
- severe chronic obstructive pulmonary disease
- History of severe traumatic brain injury
- Mild cognitive impairment assessed by the Montreal Cognitive Assessment
- Pregnancy, breastfeeding and/or refusal to use effective birth control (for women)
- Narcolepsy
- Previous adverse reaction to a hypnotic
- Current use of benzodiazepines, strong CYP3A inhibitors, or Digoxin
- Prohibited:
- Benzodiazepines
- Strong CYP3A inhibitors
- Digoxin
- Furthermore, CNS depressants (e.g., benzodiazepines, opioids, alcohol) increase the risk of CNS depression when co-administered with suvorexant and will not be allowed for safety reasons.
- Since metabolism by CYP3A is the major elimination pathway for suvorexant, concomitant use of suvorexant with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan), moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil), or strong CYP3A inducers (e.g., rifampin, carbamazepine and phenytoin) will not be allowed.
- All concomitant medication use will be monitored and documented
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5703
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822
Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
Salisbury, North Carolina, 28144
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121-1563
About this study
Official title: Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance inPosttraumatic Stress
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.
Read the detailed description
The investigators propose a multi-site parallel group, randomized, double-blind, placebo-controlled Phase IV clinical trial to test the efficacy and safety of suvorexant on trauma-related sleep disturbance and PTSD symptoms in Veterans. The investigators will use a flexible dose design of suvorexant with a 2-week titration followed by a 10-week steady-dose phase. The investigators predict that suvorexant, as compared to placebo, will result in a greater decrease in insomnia on the Insomnia Severity Index (ISI) over the 12-week trial. The investigators also predict that suvorexant, as compared to placebo, will result in a greater reduction in non-sleep PTSD symptoms in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV) CAPS-5 over the 12-week trial. Secondarily, the investigators will examine potential objectively measured wrist actigraphy as a biological mechanism of clinical improvement with as well as concomitant effects on PTSD-related nightmares using the Pittsburgh Sleep Quality Index-PTSD addendum (PSQI-A). Pending a significant effect of suvorexant on PTSD, the investigators will perform exploratory analyses to evaluate whether sleep improvement mediates the effect of suvorexant on PTSD symptoms. The investigators will also examine safety and tolerability of suvorexant compared to placebo (including depression, mood, vigor, suicidality, and daytime somnolence, psychomotor vigilance, and functional disability). Results from this study will provide substantive rationale for the use of Suvorexant in the treatment of Veterans with these concerns. This study will be the first to examine a selective orexin-receptor antagonist in a Veteran sample with PTSD. Suvorexant is an accessible, non-stigmatized medication whose use and safety has been well-established in non-mental-health settings. It has outstanding promise for treating common and distressing symptoms in Veterans as well as civilians with trauma-related sleep disturbance and PTSD.
- Being tested
- Suvorexant, Placebo
- Keywords
- Sleep Initiation and Maintenance Disorders, Stress Disorders, Posttraumatic, Suvorexant, Veterans
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SuvorexantDrug
Also called Belsomra
Suvorexant, 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.
PlaceboOther
Visibly 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.
| Study group | Role | What they receive |
|---|---|---|
| Suvorexant | Experimental | Suvorexant is a dual orexin receptor antagonist that is FDA approved to treat insomnia. Receives: Drug: Suvorexant |
| Identical Placebo | Placebo comparator | Visibly 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline to week 12
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.
Measured: Change from baseline to week 12
Secondary outcomes (2)
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.
Measured: Change from 1 week at baseline, and weeks 4, 8, and 12
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.
Measured: Change in PTSD-related nightmares across the 12 week trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start30 Aug 2019
- Primary completion30 Jun 2026
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Initiation and Maintenance DisordersStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The investigators propose a multi-site parallel group, randomized, double-blind, placebo-controlled Phase IV clinical trial to test the efficacy and safety of suvorexant on trauma-related sleep disturbance and post-traumatic stress disorder (PTSD) symptoms in Veterans. The investigators will use a flexible dose design of suvorexant with a 2-week titration followed by a 10-week steady-dose phase.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Sabra S Inslicht, PhD, Principal investigator, San Francisco VA Medical Center, San Francisco, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03642028
- Sponsor's protocol ID
- MHBB-009-17F
- Other IDs
- 1I01CX001814-01
- Status last verified
- Nov 2026
- First submitted
- 20 Aug 2018
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance inPosttraumatic Stress
- ClinicalTrials.gov ID
- NCT03642028
- Acronym / sponsor ID
- MHBB-009-17F
- Keywords
- Sleep Initiation and Maintenance Disorders, Stress Disorders, Posttraumatic, Suvorexant, Veterans
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 30 Aug 2019 (actual)
- Primary completion
- 30 Jun 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 22 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators propose a multi-site parallel group, randomized, double-blind, placebo-controlled Phase IV clinical trial to test the efficacy and safety of suvorexant on trauma-related sleep disturbance and PTSD symptoms in Veterans. The investigators will use a flexible dose design of suvorexant with a 2-week titration followed by a 10-week steady-dose phase. The investigators predict that suvorexant, as compared to placebo, will result in a greater decrease in insomnia on the Insomnia Severity Index (ISI) over the 12-week trial. The investigators also predict that suvorexant, as compared to placebo, will result in a greater reduction in non-sleep PTSD symptoms in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV) CAPS-5 over the 12-week trial. Secondarily, the investigators will examine potential objectively measured wrist actigraphy as a biological mechanism of clinical improvement with as well as concomitant effects on PTSD-related nightmares using the Pittsburgh Sleep Quality Index-PTSD addendum (PSQI-A). Pending a significant effect of suvorexant on PTSD, the investigators will perform exploratory analyses to evaluate whether sleep improvement mediates the effect of suvorexant on PTSD symptoms. The investigators will also examine safety and tolerability of suvorexant compared to placebo (including depression, mood, vigor, suicidality, and daytime somnolence, psychomotor vigilance, and functional disability). Results from this study will provide substantive rationale for the use of Suvorexant in the treatment of Veterans with these concerns. This study will be the first to examine a selective orexin-receptor antagonist in a Veteran sample with PTSD. Suvorexant is an accessible, non-stigmatized medication whose use and safety has been well-established in non-mental-health settings. It has outstanding promise for treating common and distressing symptoms in Veterans as well as civilians with trauma-related sleep disturbance and PTSD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The investigators propose a multi-site parallel group, randomized, double-blind, placebo-controlled Phase IV clinical trial to test the efficacy and safety of suvorexant on trauma-related sleep disturbance and post-traumatic stress disorder (PTSD) symptoms in Veterans. The investigators will use a flexible dose design of suvorexant with a 2-week titration followed by a 10-week steady-dose phase.
| Arm | Type | Receives |
|---|---|---|
| Suvorexant | Experimental | Drug: SuvorexantSuvorexant is a dual orexin receptor antagonist that is FDA approved to treat insomnia. |
| Identical Placebo | Placebo comparator | Other: PlaceboVisibly 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Men and women 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
- Post-traumatic stress disorder (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
- Subjects on non-exclusionary medications must be on a stable dose for at least 4 weeks prior to randomization, which includes the Selective Serotonin Reuptake Inhibitors (SSRIs) e.g.:
Key exclusion criteria (30 listed)
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol, marijuana, and/or other drug use disorder in the last 3 months
- Manic or psychotic episode in the last 5 years
- Exposure to trauma in the last 3 months
- Prominent suicidal or homicidal ideation or any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS) or increased risk of suicide that necessitates additional therapy or inpatient treatment
- Pre-existing severe sleep apnea (score >30) in the absence of adherence to effective treatment (such as CPAP or oral device) or positive screen for severe sleep apnea by type III device (score > 30)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SuvorexantAlso: BelsomraSuvorexant, 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. | Drug | Suvorexant |
| PlaceboVisibly 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. | Other | Identical Placebo |
Primary outcome
Insomnia Severity Index (ISI)
Time frame: Change from baseline to week 12
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.
Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Change from baseline to week 12
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.
2 secondary outcomes
Wrist Actigraphy
Time frame: Change from 1 week at baseline, and weeks 4, 8, and 12
Pittsburgh Sleep Quality Index-PTSD Addendum (PSQI-A)
Time frame: Change in PTSD-related nightmares across the 12 week trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabra S Inslicht, PhD principal investigator
San Francisco VA Medical Center, San Francisco, CA
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Suvorexant in people with Sleep Initiation and Maintenance Disorders and Stress Disorders, Posttraumatic, run by VA Office of Research and Development at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insomnia Severity Index (ISI) (time frame: Change from baseline to week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.