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

NCT ID: NCT03642028

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-30
• Study Completion Date: 2025-12-31

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.

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.

Conditions

Sleep Initiation and Maintenance Disorders; Stress Disorders, Posttraumatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Suvorexant

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

Group Type: EXPERIMENTAL

Suvorexant

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Belsomra

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sabra S Inslicht, PhD

Role: PRINCIPAL_INVESTIGATOR

San Francisco VA Medical Center, San Francisco, CA

Locations

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status: RECRUITING

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

Site Status: RECRUITING

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

Salisbury, North Carolina, United States

Site Status: RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sabra S Inslicht, PhD

Role: CONTACT

sabra.inslicht@va.gov

(415) 221-4810 ext. 3341

Facility Contacts

Michael Hollifield, MD

Role: primary

Michael.Hollifield@va.gov

562-967-0115

Sabra S Inslicht, PhD

Role: primary

sabra.inslicht@va.gov

415-221-4810 ext. 3341

Robin Hurley, MD

Role: primary

robin.hurley@va.gov

704-638-9000 ext. 14455

Amy Morris

Role: backup

amy.morris3@va.gov

7046389000 ext. 14392

Zhewu Wang, MD

Role: primary

zhewu.wang@va.gov

843-252-3586

Lisa McTeague, PhD

Role: backup

lisa.mcteague@va.gov

8435775011

Related Links

https://studypages.com/s/are-you-a-veteran-with-sleeping-problems-and-posttraumatic-stress-participate-in-a-clinical-research-study-from-home-601539/

Related Info

Other Identifiers

1I01CX001814-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MHBB-009-17F

Identifier Type: -

Identifier Source: org_study_id