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

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ClinicalTrials.gov Identifier: NCT02849548
Recruitment Status : Recruiting
First Posted : July 29, 2016
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
Georgetown-Howard Universities Center for Clinical and Translational Science
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Howard University

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.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: suvorexant Other: placebo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Can Blocking the Orexin System Enhance Sleep's Benefits to Therapeutic Exposure for PTSD?
Actual Study Start Date : January 3, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Suvorexant

Arm Intervention/treatment
Experimental: suvorexant
10 to 20 mg to be administered after an evening written trauma narrative exposure session.
Drug: suvorexant
First in class orexin antagonist approved by the FDA for the treatment of insomnia
Other Name: Belsomra

Placebo Comparator: Placebo pill
A pill without active ingredients
Other: placebo
Pill with inactive ingredients




Primary Outcome Measures :
  1. Change in the Clinician Administered PTSD Scale for DSM-5 score [ Time Frame: 1 week ]
    A structured clinical interview used to assess PTSD symptom severity for the preceding week. Items are scored on a 5-point scale, and a total score is obtained by summing the 20-symptom items, with higher scores indicating greater PTSD symptom severity.


Secondary Outcome Measures :
  1. Change in highest pulse rate from an evening written narrative exposure session to a session in the following morning [ Time Frame: 12 hours ]
    The average pulse rate for a 5-minute baseline and each 2-minute epoch during 30-min written narrative exposure will be computed. The highest average pulse rate for each session will be identified and corrected for the baseline pulse rate of the session by subtracting the baseline average pulse rate from the highest average pulse rate within the session.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02849548


Contacts
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Contact: Imani Brown, MPH 202-865-7185 WSHStudy@howard.edu

Locations
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United States, District of Columbia
Clinical Research Unit; Howard University Hospital Recruiting
Washington, District of Columbia, United States, 20060
Contact: Alice Ukaegbu, DMP MSN    202-865-7276    aukaegbu@howard.edu   
Sponsors and Collaborators
Howard University
Georgetown-Howard Universities Center for Clinical and Translational Science
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Ihori Kobayashi, Ph.D. Howard University

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Responsible Party: Howard University
ClinicalTrials.gov Identifier: NCT02849548     History of Changes
Other Study ID Numbers: GHUCCTS2016-0377
1K01MH110647-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 29, 2016    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Suvorexant
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Orexin Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action