Suvorexant and Sleep's Benefits to Therapeutic Exposure for Posttraumatic Stress Disorder

NCT ID: NCT02849548

Last Updated: 2023-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-03
• Study Completion Date: 2021-05-19

Brief Summary

The purpose of this study is to examine effects of blocking the orexin system with suvorexant after exposure-based intervention for posttraumatic stress disorder (PTSD) on sleep, PTSD symptoms, and intersession habituation.

Detailed Description

Cognitive behavioral therapies (CBT) that include exposure to trauma memories are considered first line treatments for PTSD. However, approximately 1/3 of patients who complete CBT for PTSD do not achieve remission, and hyperarousal symptoms including sleep disturbances are less responsive to CBT than other PTSD symptoms. Despite these limitations, CBT outcomes are generally superior to outcomes of pharmacotherapy. It is, therefore, imperative to identify strategies to improve effectiveness of treatments for PTSD, particularly hyperarousal symptoms.

Disturbed sleep is common in PTSD. Studies of PTSD and anxiety and mood disorders have shown that impaired sleep before psychotherapy predicted less favorable responses. Sleep has been implicated in learning processes that are a key to adaptive processing of trauma memories such as extinction learning and generalization of extinction. Our recent PTSD study showed that preserved slow-wave sleep (SWS), less increase in rapid-eye-movement (REM) density, and reduced wake after sleep onset (WASO) during sleep following an evening session of written narrative exposure (WNE: writing about one's traumatic experience) was associated with greater PTSD symptom reduction. These findings suggest that increased nocturnal arousal compromises sleep's benefits to emotional processing of trauma memories. Identifying strategies to reduce nocturnal arousal and promote sleep characteristics associated with emotional adaptation could enhance PTSD treatment outcomes.

Orexins are neuropeptides implicated in regulating both sleep/wakefulness and emotional behaviors, including anxiety. Inhibiting the orexin system promoted slow-wave patterns and reduced wake in animal models. The first orexin receptor antagonist (suvorexant) was recently approved for treatment of insomnia. Suvorexant reduced WASO and latency to persistent sleep and increased SWS and REM sleep in humans with insomnia. In addition, administrations of orexin-A increased anxiety-like behaviors in rodents, and administrations of an orexin receptor-1 antagonist to mice facilitated extinction of conditioned fear, an animal model of recovery from PTSD and anxiety disorders.

Objective: To examine effects of blocking the orexin system with suvorexant after WNE on sleep, PTSD symptoms, and intersession habituation.

The investigators will utilize the WNE paradigm in which participants with PTSD write about their traumatic experiences in the evening and morning sessions with intervening sleep. Suvorexant or placebo will be administered after the evening WNE, and sleep will be recorded.

The investigators hypothesize that 1) Suvorexant will promote the sleep characteristics that have been associated with more favorable treatment outcomes and emotional adaptation (e.g., increased SWS and REM sleep, reduced WASO) compared with placebo; 2) Participants given suvorexant will have greater PTSD symptom reduction and intersession habituation indexed by reduction of maximum pulse rate compared with participants given placebo; and 3) The greater PTSD symptom reduction and intersession habituation in the suvorexant group will be accounted for by effects of the medication on sleep.

Conditions

Posttraumatic Stress Disorder

Study Design

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

Study Groups

suvorexant

10 to 20 mg to be administered after an evening written trauma narrative exposure session.

Group Type: EXPERIMENTAL

suvorexant

Intervention Type: DRUG

First in class orexin antagonist approved by the FDA for the treatment of insomnia

Placebo pill

A pill without active ingredients

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Pill with inactive ingredients

Interventions

suvorexant

First in class orexin antagonist approved by the FDA for the treatment of insomnia

Intervention Type: DRUG

placebo

Pill with inactive ingredients

Intervention Type: OTHER

Other Intervention Names

Belsomra

Eligibility Criteria

Inclusion Criteria

• Adult men and women (age 18 or older) who meet the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for PTSD.

Exclusion Criteria

• Medical or psychiatric conditions that require consistent use of medication that affects sleep or psychiatric symptoms, except for hormonal contraceptives
• Any persistent medical condition that affects sleep
• Inability to remember most details of the index event
• Diagnosis of a sleep disorder other than insomnia including polysomnography findings of apnea/hypopnea index > 10/hour
• Consumption of more caffeine than 5 cups of coffee/day equivalent
• Smoking > 20 cigarettes/day
• Habitual bedtimes after 3AM, habitual rise times after 10AM, or average napping > 2 hour/day in a given week
• Moderate or severe alcohol use disorder within the past 6 months or moderate or severe drug use disorder within the past year
• Positive urine toxicology for illicit drugs including cannabis
• A history of psychotic disorders or bipolar disorder
• Current depression with history of recurrent depression that precedes exposure to a traumatic event
• Suicidal ideation with intent to act or with specific plan and intent in the past 6 months [Type 4 - 5 ideation on the Columbia Suicide Severity Rating Scale (C-SSRS)] or history of a suicide attempt
• Completion of exposure-based therapy targeting the index trauma
• Pregnancy or breast feeding
• Known sensitivity or allergy to an orexin receptor antagonist
• Limited ability to read or write English.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Georgetown-Howard Universities Center for Clinical and Translational Science

OTHER

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Howard University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ihori Kobayashi, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Howard University

Locations

Clinical Research Unit; Howard University Hospital

Washington D.C., District of Columbia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1K01MH110647-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GHUCCTS2016-0377

Identifier Type: -

Identifier Source: org_study_id