Recruiting

SuvorexantSuvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance in Posttraumatic Stress

Sponsor:

VA Office of Research and Development

Code:

NCT03642028

Conditions

Sleep Initiation and Maintenance Disorders

Stress Disorders, Posttraumatic

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Suvorexant

Placebo

Study Details

Brief 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 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.

Conditions

Sleep Initiation and Maintenance Disorders

Stress Disorders, Posttraumatic

Study ID

NCT03642028

Start date

Aug 30, 2019

Status verified date

Jul, 2025

Completion date

Dec 31, 2025

Anticipated

Primary completion date

Dec 31, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
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
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

Exclusion Criteria:

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
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

Study Design

Enrollment

190 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Suvorexant

Suvorexant is a dual orexin receptor antagonist that is FDA approved to treat insomnia.

placebo comparator: Identical Placebo

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.

Interventions

Suvorexant

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.

Placebo

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.

Primary outcome measure

Insomnia Severity Index (ISI) [ Time Frame: Change from baseline to week 12 ]
Clinician Administered PTSD Scale for DSM-5 (CAPS-5) [ Time Frame: Change from baseline to week 12 ]

Central Contacts and Locations

Central contacts

Sabra S Inslicht, PhD

(415) 221-4810 sabra.inslicht@va.gov

Locations

VA Long Beach Healthcare System, Long Beach, CA

Recruiting

Long Beach, California, United States, 90822

Contacts

Michael Hollifield, MD

562-967-0115 Michael.Hollifield@va.gov

San Francisco VA Medical Center, San Francisco, CA

Recruiting

San Francisco, California, United States, 94121-1563

Contacts

Sabra S Inslicht, PhD

415-221-4810 sabra.inslicht@va.gov

Principal Investigator:

Sabra S Inslicht, PhD

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Recruiting

Salisbury, North Carolina, United States, 28144

Contacts

Robin Hurley, MD

704-638-9000 robin.hurley@va.gov

Amy Morris

7046389000 amy.morris3@va.gov

Ralph H. Johnson VA Medical Center, Charleston, SC

Recruiting

Charleston, South Carolina, United States, 29401-5703

Contacts

Zhewu Wang, MD

843-252-3586 zhewu.wang@va.gov

Lisa McTeague, PhD

8435775011 lisa.mcteague@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Jul 18, 2025

Last verified

Jul, 2025

Keywords

Sleep Initiation and Maintenance Disorders
Stress Disorders, Posttraumatic
Suvorexant
Veterans

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2025-07-18.