The Effects of Orexin Antagonism on Fear Extinction in PTSD

NCT06788522 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: MHBP-006-24S
• Study Type: interventional
• Target: 40,120
• Locations: 1 country
• Sites: 2

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

Keywords

Fear conditioning; PTSD; Insomnia

Outcome Measures

Primary Outcomes (7)

• enrollment

  Goal of enrolling 40 individuals to achieve a total of 30 completers by the end of month 23.

  Month 4-23

• Medication Adherence

  Pill count and adherence to instructions over 7 study nights

  Month 4-23

• side effect reports

  SAEs

  Month 4-23

• Post-randomization drop out

  Post-randomization drop-out rates

  Month 4-23

• Fear conditioning and extinction

  Fear conditioning (greater SC responses to CS+ cues vs CS- cues) and fear extinction (differential SC responses to CS+ and CS- cues that diminish over repeated trials) in the combined sample

  Month 4-23

• Rates of technical malfunction

  Rates of technical malfunction (SC levels that are missing or \<.02 microsiemens) and or non-responding to the UCS (e.g., SCR\<.05 microsiemens)

  Month 4-23

• Electrodermal Activity

  Differential SC responses to CS+ and CS- cues during extinction retention and 2) during reinstatement.

  Years 2-7

Secondary Outcomes (2)

• Insomnia Severity Index

  Years 2-7

• Sleep EEG

  Years 2-7

Study Arms (2)

Suvorexant

EXPERIMENTAL

Suvorexant pills (10-20 mg)

Drug: Suvorexant

Placebo

PLACEBO COMPARATOR

Matching placebo pills

Drug: Placebo

Interventions

Suvorexant DRUG

Suvorexant pills (10-20 mg)

Suvorexant

Placebo DRUG

Matching placebo pills

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:

• (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
• sertraline
• paroxetine
• fluoxetine
• fluvoxamine
• citalopram
• escitalopram
• Serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g.):

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121-1563, United States

Location

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5703, United States

Location

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: Participants will be blindly assigned to treatment according to a randomization schedule generated by the study biostatistician using a computerized allocation schedule system. Study investigators, staff, and participants will remain blinded to treatment allocation throughout the study. A study physician will prescribe the study drug and will remain blind to treatment assignment for the study duration.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: In line with the CSRD Combined Proof of Concept and Clinical Merit Review Award mechanism, this proposal aims to conduct a proof-of-concept study that will lead to a larger clinical trial to further the evidence base for the intervention. For this study, the investigators propose a home-based multi-day remote fear conditioning experiment where nightly doses of suvorexant or placebo will be administered following extinction training over the subsequent 6 nights. In phase 1, the investigators will demonstrate our remote fear conditioning task and assess its feasibility by conducting a pilot study in which the investigators will enroll and randomize 40 Veterans with PTSD and insomnia. The design for Phase 1 (and Phase 2) will involve a double-blind, randomized, placebo-controlled experiment of suvorexant on fear extinction in a home-based classical aversive conditioning paradigm in male and female Veterans with PTSD and insomnia.

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: January 23, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)