Recruiting

Phase 4

SuvorexantThe Effects of Orexin Antagonism on Fear Extinction in PTSD

Sponsor:

VA Office of Research and Development

Code:

NCT06788522

Conditions

Insomnia

PTSD

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Suvorexant

Placebo

Study Details

Brief summary:

PTSD affects approximately 22% of Veterans who have served in Iraq and Afghanistan. Symptoms of PTSD may include re-experiencing, avoidance of trauma reminders, negative thoughts or feelings, and hyperarousal, such as increased startle reactivity and disturbed sleep. Treatments for PTSD are based on fear extinction principles in which individuals are repeatedly exposed a feared cue in the absence of danger, resulting in diminishing physiological reactions, a process believed to underlie recovery from PTSD. Studies suggest that orexin, a wake-promoting neuropeptide, may enhance fear extinction. This study will examine whether suvorexant, a selective orexin-receptor antagonist, will enhance fear extinction in Veterans with PTSD and insomnia. Finding a role for orexins in fear extinction will support the rationale for its further evaluation in the treatment of PTSD. Suvorexant is an accessible, safe medication that has been well-established in treating insomnia. It has outstanding promise for treating common and distressing symptoms in Veterans with PTSD.

Conditions

Insomnia

PTSD

Study ID

NCT06788522

Start date

Jul 1, 2026

Status verified date

Nov, 2026

Completion date

Jun 30, 2032

Anticipated

Primary completion date

Mar 1, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

(same for Phase 1 and Phase 2):

men and women
a history of US military service
capable of reading and understanding English
able to provide written informed consent
Criterion A event meets DSM-5 criteria and occurred during military service, including combat and military sexual trauma
Chronic full PTSD diagnosis >3 months duration as indexed by CAPS-5 at screening, and CAPS-5 score > 30
Insomnia indicated by insomnia severity index (ISI) score > 14
Subjects on non-exclusionary medications, and must be on a stable dose for at least 4 weeks prior to randomization, including 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

Exclusion Criteria:

Moderate or severe DSM-5 alcohol or cannabis use disorder in the last 3 months

Mild alcohol use disorder with abstinence of 30 days will be allowed
Mild marijuana use disorder will be allowed with abstinence for one week prior to participation
Any other DSM-5 drug use disorder in the last 3 months will be excluded
Lifetime bipolar disorder I or II, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features
Exposure to trauma in the last 3 months
Use of exclusionary antidepressant (trazodone, mirtazapine, doxepin, tricyclics), mood stabilizers (e.g., lithium), antipsychotic medication
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 moderate sleep apnea or positive screen for sleep apnea by type III device (AHI>15) in the absence of adherence to effective treatment (such as CPAP or oral device)
Night shift work or extreme morning or evening tendencies in order to avoid the impact of circadian factors on subjective and objective sleep measures
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 as assessed by the Ohio State University Traumatic Brain Injury Identification Method (OSU-TBI ID)
Uncorrected hearing impairment
Mild cognitive impairment assessed by the Montreal Cognitive Assessment (MOCA)
Pregnancy, breastfeeding and/or refusal to use effective birth control (for women)
Previous adverse reaction to a hypnotic
Current use of benzodiazepines, strong inhibitors of CYP3A, or Digoxin

The investigators will require that all participants do not consume heavy amounts of alcohol per week (>7 drinks for women, >14 drinks for men) or use illicit drugs for one week prior to participation

Study Design

Enrollment

40120 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Suvorexant

Suvorexant pills (10-20 milligrams)

placebo comparator: Placebo

Matching placebo pills

Interventions

Suvorexant

Suvorexant pills (10-20 milligrams)

Placebo

Matching placebo pills

Primary outcome measure

Enrollment [ Time Frame: Month 4-23 ]
Medication Adherence [ Time Frame: Month 4-23 ]
Side effect reports [ Time Frame: Month 4-23 ]
Post-randomization drop out [ Time Frame: Month 4-23 ]
Fear conditioning and extinction [ Time Frame: Month 4-23 ]
Rates of technical malfunction [ Time Frame: Month 4-23 ]
Electrodermal Activity [ Time Frame: Years 2-7 ]

Central Contacts and Locations

Central contacts

Sabra S Inslicht, PhD

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

Locations

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

More Information

Sponsor

VA Office of Research and Development

Last update posted

Nov 5, 2026

Last verified

Nov, 2026

Keywords

Fear conditioning
PTSD
Insomnia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-06. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-11-05. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.