Orexin-blocking treatment to help fear extinction in PTSD and insomnia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 4 interventional trial testing suvorexant versus placebo in veterans with PTSD and insomnia. The study uses a remote, multi-day fear conditioning and extinction protocol after nightly dosing, to see if blocking orexin receptors can enhance extinction learning. Researchers will assess feasibility, tolerability, adherence, and retention, along with learning outcomes and safety. The approach builds on preclinical data suggesting orexin involvement in wakefulness and fear extinction, aiming to translate these findings to humans with PTSD. The trial is conducted at VA medical centers in San Francisco and Charleston and seeks to establish a proof-of-concept for remote fear conditioning procedures in this population.

Why it matters

Who can join: the full rules

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

Where it's running

• San Francisco VA Medical Center, San Francisco, CA
  San Francisco, California, United States Recruiting
• Ralph H. Johnson VA Medical Center, Charleston, SC
  Charleston, South Carolina, United States Not yet recruiting

Study contacts

• Principal investigator: Sabra S Inslicht, PhD — San Francisco VA Medical Center, San Francisco, CA
• Study coordinator: Sabra S Inslicht, PhD
• Email: sabra.inslicht@va.gov
• Phone: (415) 221-4810

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.