Suvorexant and Trauma Related Insomnia
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|ClinicalTrials.gov Identifier: NCT02704754|
Recruitment Status : Completed
First Posted : March 10, 2016
Results First Posted : February 15, 2023
Last Update Posted : February 15, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Insomnia Posttraumatic Stress Disorder||Drug: suvorexant Other: placebo||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Suvorexant and Trauma Related Insomnia|
|Actual Study Start Date :||May 1, 2016|
|Actual Primary Completion Date :||April 30, 2021|
|Actual Study Completion Date :||April 30, 2021|
10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime.
First in class orexin antagonist recently approved by the FDA for the treatment of insomnia
Other Name: Belsomra
Placebo Comparator: Placebo pill
A pill without active ingredients
Randomization occurs 1:1 with stratification for gender and PTSD status.
Pill with inactive ingredients
- 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.
- 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). ]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.
- Polysomnographically Measured Wake After Sleep Onset [ Time Frame: Baseline values minus the values at 2 weeks. ]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.
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|Ages Eligible for Study:||18 Years to 55 Years (Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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;
- 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.
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): NCT02704754
|United States, District of Columbia|
|Clinical Research Unit; Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|Principal Investigator:||Thomas A Mellman, M.D.||Howard University|
Documents provided by Howard University:
|Responsible Party:||Howard University|
|Other Study ID Numbers:||
|First Posted:||March 10, 2016 Key Record Dates|
|Results First Posted:||February 15, 2023|
|Last Update Posted:||February 15, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Reasonable requests will be accomodated via emailing the principal investigator.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
|Time Frame:||now, for 5 years|
|Access Criteria:||reasonable request made directly to investigator|
Sleep Initiation and Maintenance Disorders
Stress Disorders, Post-Traumatic
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Stress Disorders, 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