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

NCT03642028 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: MHBB-009-17F1I01CX001814-01
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 4

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

Keywords

Sleep Initiation and Maintenance Disorders; Stress Disorders, Posttraumatic; Suvorexant; Veterans

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Change from baseline to week 12

Secondary Outcomes (2)

• Wrist Actigraphy

  Change from 1 week at baseline, and weeks 4, 8, and 12

• Pittsburgh Sleep Quality Index-PTSD Addendum (PSQI-A)

  Change in PTSD-related nightmares across the 12 week trial

Other Outcomes (1)

• Clinical Global Impression (CGI)

  Change across the 12 week trial

Study Arms (2)

Suvorexant

EXPERIMENTAL

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

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.

Other: Placebo

Interventions

Suvorexant DRUG

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.

Also known as: Belsomra

Suvorexant

Placebo OTHER

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.

Identical Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Sertraline
• Paroxetine
• Fluoxetine
• Fluvoxamine
• Citalopram
• Escitalopram
• Serotonin-norepinephrine reuptake inhibitors (SNRIs), e.g.:
• Desvenlafaxine
• Duloxetine
• Levomilnacipran
• Venlafaxine

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

RECRUITING

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121-1563, United States

RECRUITING

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

Salisbury, North Carolina, 28144, United States

RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5703, United States

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Study Officials

• Sabra S Inslicht, PhD

  San Francisco VA Medical Center, San Francisco, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabra S Inslicht, PhD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The blind will be maintained through completion of the entire study at all sites and will only be broken once data are cleaned to an acceptable level of quality, except for medical necessity.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 22, 2018
• Study Start: August 30, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)