Suvorexant and Sleep's Benefits to Therapeutic Exposure for Posttraumatic Stress Disorder
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|ClinicalTrials.gov Identifier: NCT02849548|
Recruitment Status : Completed
First Posted : July 29, 2016
Results First Posted : June 2, 2023
Last Update Posted : June 2, 2023
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|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)|
|Actual Enrollment :||27 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|
|Actual Primary Completion Date :||May 17, 2021|
|Actual Study Completion Date :||May 19, 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
- The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2 [ Time Frame: 2 weeks ]A structured clinical interview used to assess posttraumatic stress disorder (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. The total scores range from 0 - 80.
- The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session [ Time Frame: 1 week ]The subjective unit of distress scale (SUDS) is a numerical scale that is administered orally. It ranges from 0 - 100 in which 0 indicates no stress at all, and 100 indicates the highest stress level. The highest SUDS score for each session was identified and corrected for the baseline SUDS of the session by subtracting the baseline SUDS from the SUDS within the session; therefore, the baseline-corrected SUDS scores can range from 0 to 100.
- The Baseline-corrected Highest Pulse Rate Across at the Last Written Narrative Exposure Session [ Time Frame: 1week ]The average pulse rate for a 5-minute baseline and each 2-minute epoch during 30-min written narrative exposure were computed. The highest average pulse rate for each session was 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. The Baseline-corrected highest pulse rate values reported here are small because the baseline average pulse rate of the session was subtracted from the highest 2-minute average pulse rate of the session.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- 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.
- 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.
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
|United States, District of Columbia|
|Clinical Research Unit; Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|Principal Investigator:||Ihori Kobayashi, Ph.D.||Howard University|
Documents provided by Howard University:
|Responsible Party:||Howard University|
|Other Study ID Numbers:||
1K01MH110647-01A1 ( U.S. NIH Grant/Contract )
|First Posted:||July 29, 2016 Key Record Dates|
|Results First Posted:||June 2, 2023|
|Last Update Posted:||June 2, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||The de-identified final dataset will include scores/values obtained through self-report survey, interviews, narrative writing, pulse recording, and polysomnography. Even though personally identifiable information will be removed from the final dataset, there remains the possibility that participants' identities are deduced from information about their traumatic events. Therefore, participants' trauma narratives and details of traumatic events disclosed during the writing sessions and interviews will not be shared.|
Informed Consent Form (ICF)
|Time Frame:||Data will be available after the first publication is published.|
|Access Criteria:||Given the highly sensitive nature of the data which includes participants' mental and physical health information, we will make the de-identified data available to users only under a data-sharing agreement that: 1) the data will be used only for research purposes; 2) users will not identify any individual participant; 3) users utilize appropriate computer technology to ensure data security; and 4) users destroy or return the data after analyses are completed.|
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Orexin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action