InsomniaPhase 4NCT02704754
Suvorexant and Trauma Related Insomnia
A Phase 4 study testing suvorexant in people with Insomnia and Posttraumatic Stress Disorder, run by Howard University at 1 site in United States.
Trial summary
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Insomnia, 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
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2016to 30 Apr 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 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Physically healthy adults age 18-55 who meet DSM-5 criteria for insomnia and Criterion A (exposure to a traumatic event) for PTSD. The index trauma must have occurred within the past 5 years and at least 3 months before enrolling, and insomnia symptoms must have started or worsened after the exposure to the index trauma
Who cannot join
- Psychiatric disorders other than insomnia, PTSD and specific phobias; including bipolar and psychotic disorders and meeting criteria for DSM-5 moderate alcohol or drug use disorders within the past year.
- Diagnosis of a sleep disorder other than insomnia including PSG findings of apnea/hypopnea or periodic limb movement indices > 10/hour;
- Medical conditions that require consistent use of medication or compromise sleep;
- History of moderate to severe traumatic brain injury or mild traumatic brain injury with ongoing post-concussive symptoms;
- 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) or a concerning history of prior suicidal behavior.
- Caffeine use exceeding 5 cups of coffee per day or its equivalent;
Show all 9Show fewer
- Habitual bedtimes after 3 AM, habitual rise times after 10 AM, or habitual napping > 1hour/day;
- Pregnancy or breastfeeding, or expecting to conceive while in study;
- Positive urine toxicology.
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
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved drugs has a unique mechanism of action that may be well suited for targetting arousal at night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for insomnia that developed in relation to trauma exposure, utilizing a placebo control, and polysomnography to identify biomarkers of response, in a six week trial.
Read the detailed description
Disturbed sleep is one of the most common and distressing responses to exposure to severe trauma and can persist in many of those affected with and without accompanying posttraumatic stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are prevalent in trauma-exposed populations including PTSD, depression, and physical health conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not typically differentiated in studies characterizing insomnia and its treatment, and insomnia accompanying PTSD has been shown to be relatively refractory to the treatments that are established for PTSD. Thus treatment of TRI presents an unmet need that has implications for the large and growing groups of people exposed to trauma in terms of relieving distress and preventing further psychiatric and medical morbidity.
Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD is developing, and during its more acute stages. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists dampen the activity of a specific arousal enhancing system in the brain during sleep. In rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow wave and REM activity (in contrast with traditional hypnotics which can diminish both). Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and its tolerability in these populations. We will include polysomnography (PSG) in order to have objective sleep outcomes and probe potential mechanisms and biomarkers predicting response. The proposed study will meet the objective below and test the following hypotheses:
Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for insomnia and who identify a severely threatening event (DSM criterion A trauma) as a precipitant or a factor that significantly exacerbated their sleep disturbance.
The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of sleep efficiency will be increased in the group receiving suvorexant compared with the group receiving placebo.
The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated.
Exploratory analyses will include comparison of response patterns among those with versus without significant symptoms of PTSD and relationships between increased in slow wave and rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms.
Adverse experiences and the tolerability of suvorexant in the recruited population with TRI will also be evaluated.
- Conditions
- Insomnia, Posttraumatic Stress Disorder
- Being tested
- suvorexant, placebo
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, 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 recently approved by the FDA for the treatment of insomnia
placeboOther
Pill with inactive ingredients
| Study group | Role | What they receive |
|---|---|---|
| suvorexant | Experimental | 10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime. Receives: Drug: suvorexant |
| Placebo pill | Placebo comparator | A pill without active ingredients
Randomization occurs 1:1 with stratification for gender and PTSD status. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Insomnia Severity Index Score From Baseline.
A seven-item measure used to evaluate insomnia severity for the preceding two weeks. Items are scored on a 5-point scale and a total score ranging between 0 and 28 is obtained by summing the seven items, with higher scores indicating greater insomnia severity.
Measured: Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the "last observation" was 5 weeks).
Secondary outcomes (2)
Change in Clinician Administered PTSD Scale Score
Evaluates the frequency and intensity of each of the diagnostic symptoms of PTSD including nightmares and insomnia, total score was used which is a summation of all item scores, scores range between 0 to 80 with higher scores indicating more severe symptoms.
Measured: Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the "last observation" was 5 weeks).
Polysomnographically Measured Wake After Sleep Onset
Polysomnography will provide objective measures of sleep, wake after sleep onset is the amount of wake time that occurs after initially falling asleep to the final awakening for the total sleep period measured in minutes.
Measured: Baseline values minus the values at 2 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study start1 May 2016
- Primary completion30 Apr 2021
- Study completion30 Apr 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InsomniaStudies 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Howard University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Thomas A Mellman, M.D., Principal investigator, Howard University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02704754
- Sponsor's protocol ID
- GHUCCTS2015-1333
- Status last verified
- Jan 2023
- First submitted
- 17 Feb 2016
- Last updated
- 15 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Reasonable requests will be accomodated via emailing the principal investigator.
Publications
Mellman TA, Birku K, Sandhu I, Lavela P, Kobayashi I. Evaluation of suvorexant for trauma-related insomnia. Sleep. 2022 May 12;45(5):zsac068. doi: 10.1093/sleep/zsac068. Epub 2022 Mar 18.
PubMed 35554590
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Suvorexant and Trauma Related Insomnia
- ClinicalTrials.gov ID
- NCT02704754
- Acronym / sponsor ID
- GHUCCTS2015-1333
- Conditions
- Insomnia, Posttraumatic Stress Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Howard UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 May 2016 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 10 Mar 2016 (estimated)
- Results
- Posted 15 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved drugs has a unique mechanism of action that may be well suited for targetting arousal at night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for insomnia that developed in relation to trauma exposure, utilizing a placebo control, and polysomnography to identify biomarkers of response, in a six week trial.
Detailed description
Disturbed sleep is one of the most common and distressing responses to exposure to severe trauma and can persist in many of those affected with and without accompanying posttraumatic stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are prevalent in trauma-exposed populations including PTSD, depression, and physical health conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not typically differentiated in studies characterizing insomnia and its treatment, and insomnia accompanying PTSD has been shown to be relatively refractory to the treatments that are established for PTSD. Thus treatment of TRI presents an unmet need that has implications for the large and growing groups of people exposed to trauma in terms of relieving distress and preventing further psychiatric and medical morbidity.
Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD is developing, and during its more acute stages. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists dampen the activity of a specific arousal enhancing system in the brain during sleep. In rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow wave and REM activity (in contrast with traditional hypnotics which can diminish both). Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and its tolerability in these populations. We will include polysomnography (PSG) in order to have objective sleep outcomes and probe potential mechanisms and biomarkers predicting response. The proposed study will meet the objective below and test the following hypotheses:
Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for insomnia and who identify a severely threatening event (DSM criterion A trauma) as a precipitant or a factor that significantly exacerbated their sleep disturbance.
The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of sleep efficiency will be increased in the group receiving suvorexant compared with the group receiving placebo.
The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated.
Exploratory analyses will include comparison of response patterns among those with versus without significant symptoms of PTSD and relationships between increased in slow wave and rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms.
Adverse experiences and the tolerability of suvorexant in the recruited population with TRI will also be evaluated.
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: suvorexant10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime. |
| Placebo pill | Placebo comparator | Other: placeboA pill without active ingredients Randomization occurs 1:1 with stratification for gender and PTSD status. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Physically healthy adults age 18-55 who meet DSM-5 criteria for insomnia and Criterion A (exposure to a traumatic event) for PTSD. The index trauma must have occurred within the past 5 years and at least 3 months before enrolling, and insomnia symptoms must have started or worsened after the exposure to the index trauma
Key exclusion criteria (9 listed)
- Psychiatric disorders other than insomnia, PTSD and specific phobias; including bipolar and psychotic disorders and meeting criteria for DSM-5 moderate alcohol or drug use disorders within the past year.
- Diagnosis of a sleep disorder other than insomnia including PSG findings of apnea/hypopnea or periodic limb movement indices > 10/hour;
- Medical conditions that require consistent use of medication or compromise sleep;
- History of moderate to severe traumatic brain injury or mild traumatic brain injury with ongoing post-concussive symptoms;
- 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) or a concerning history of prior suicidal behavior.
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 recently approved by the FDA for the treatment of insomnia | Drug | suvorexant |
| placeboPill with inactive ingredients | Other | Placebo pill |
Primary outcome
Change in Insomnia Severity Index Score From Baseline.
Time frame: Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the "last observation" was 5 weeks).
A seven-item measure used to evaluate insomnia severity for the preceding two weeks. Items are scored on a 5-point scale and a total score ranging between 0 and 28 is obtained by summing the seven items, with higher scores indicating greater insomnia severity.
2 secondary outcomes
Change in Clinician Administered PTSD Scale Score
Time frame: Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the "last observation" was 5 weeks).
Polysomnographically Measured Wake After Sleep Onset
Time frame: Baseline values minus the values at 2 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35554590Mellman TA, Birku K, Sandhu I, Lavela P, Kobayashi I. Evaluation of suvorexant for trauma-related insomnia. Sleep. 2022 May 12;45(5):zsac068. doi: 10.1093/sleep/zsac068. Epub 2022 Mar 18.
- Individual participant dataSharing planned: Yes. Reasonable requests will be accomodated via emailing the principal investigator.
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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.
Thomas A Mellman, M.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 Insomnia and 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 9 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 15 Feb 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 15 Feb 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?
Change in Insomnia Severity Index Score From Baseline. (time frame: Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the "last observation" was 5 weeks).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02704754, which also lists 1 linked publication.
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 15 Feb 2023.