Posttraumatic Stress DisorderPhase 4NCT02849548
Suvorexant and Sleep's Benefits to Therapeutic Exposure for Posttraumatic Stress Disorder
A Phase 4 study testing suvorexant in people with Posttraumatic Stress Disorder, run by Howard University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- suvorexant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2017to 19 May 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Unit; Howard University Hospital
Washington D.C., District of Columbia, 20060
About this study
Official title: Can Blocking the Orexin System Enhance Sleep's Benefits to Therapeutic Exposure for PTSD?
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.
Read the 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
- Being tested
- suvorexant, placebo
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
suvorexantDrug
Also called Belsomra
First in class orexin antagonist approved by the FDA for the treatment of insomnia
placeboOther
Pill with inactive ingredients
| Study group | Role | What they receive |
|---|---|---|
| suvorexant | Experimental | 10 to 20 mg to be administered after an evening written trauma narrative exposure session. Receives: Drug: suvorexant |
| Placebo pill | Placebo comparator | A pill without active ingredients Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2
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.
Measured: 2 weeks
Secondary outcomes (2)
The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session
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.
Measured: 1 week
The Baseline-corrected Highest Pulse Rate Across at the Last Written Narrative Exposure Session
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.
Measured: 1week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2016 (estimated)
- Study start3 Jan 2017
- Primary completion17 May 2021
- Study completion19 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Howard University
- Sponsor type
- University, hospital or other
- Collaborators
- Georgetown-Howard Universities Center for Clinical and Translational Science, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Ihori Kobayashi, Ph.D., Principal investigator, Howard University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02849548
- Sponsor's protocol ID
- GHUCCTS2016-0377
- Other IDs
- 1K01MH110647-01A1
- Status last verified
- May 2023
- First submitted
- 27 Jul 2016
- Last updated
- 2 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Blocking the Orexin System Enhance Sleep's Benefits to Therapeutic Exposure for PTSD?
- ClinicalTrials.gov ID
- NCT02849548
- Acronym / sponsor ID
- GHUCCTS2016-0377
- Conditions
- Posttraumatic Stress Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Howard UniversityUniversity, hospital or other
- Collaborators
- Georgetown-Howard Universities Center for Clinical and Translational Science, National Institute of Mental Health (NIMH)
- Study start
- 3 Jan 2017 (actual)
- Primary completion
- 17 May 2021 (actual)
- Study completion
- 19 May 2021 (actual)
- First posted
- 29 Jul 2016 (estimated)
- Results
- Posted 2 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| suvorexant | Experimental | Drug: suvorexant10 to 20 mg to be administered after an evening written trauma narrative exposure session. |
| Placebo pill | Placebo comparator | Other: placeboA pill without active ingredients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| suvorexantAlso: BelsomraFirst in class orexin antagonist approved by the FDA for the treatment of insomnia | Drug | suvorexant |
| placeboPill with inactive ingredients | Other | Placebo pill |
Primary outcome
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.
2 secondary outcomes
The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session
Time frame: 1 week
The Baseline-corrected Highest Pulse Rate Across at the Last Written Narrative Exposure Session
Time frame: 1week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ihori Kobayashi, Ph.D. principal investigator
Howard University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing suvorexant in people with Posttraumatic Stress Disorder, run by Howard University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2 (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.