NCT06788522 The Effects of Orexin Antagonism on Fear Extinction in PTSD

Eligibility & Interventions

Eligibility Fast-Check

Enter your details for a quick preliminary check. This does not replace medical advice.

What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 4 studies follow an already-approved treatment in real-world conditions to monitor long-term safety and effectiveness.

This trial targets 40,120 participants in total. It began in 2026-07-01 with a primary completion date of 2032-03-01.

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.

Eligibility Criteria

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

Contact & Investigator

Frequently Asked Questions

Related Trials

Related Intelligence Guides

In-depth guides covering this condition's trials, eligibility, and what to expect.