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
|Condition or disease||Intervention/treatment||Phase|
|Posttraumatic Stress Disorder||Drug: suvorexant Other: placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|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|
10 to 20 mg to be administered after an evening written trauma narrative exposure session.
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
Pill with inactive ingredients
- 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.
- 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.
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
|Contact: Imani Brown, MPH||202-865-7185||WSHStudy@howard.edu|
|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 firstname.lastname@example.org|
|Principal Investigator:||Ihori Kobayashi, Ph.D.||Howard University|