Posttraumatic Stress Disorder
Conditions
Brief 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.
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.
Interventions
DRUGsuvorexant
First in class orexin antagonist approved by the FDA for the treatment of insomnia
OTHERplacebo
Pill with inactive ingredients
Sponsors
Georgetown-Howard Universities Center for Clinical and Translational Science
National Institute of Mental Health (NIMH)
Howard University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
\- 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session | 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant 10 to 20 mg to be administered after an evening written trauma narrative exposure session.
suvorexant: First in class orexin antagonist approved by the FDA for the treatment of insomnia | 13 |
| Placebo Pill A pill without active ingredients
placebo: Pill with inactive ingredients | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Suvorexant | Total | Placebo Pill |
|---|---|---|---|
| 1-week Clinician Administered PTSD Scale for DSM-5 (CAPS-5) | 23.2 units on a scale STANDARD_DEVIATION 7.8 | 25.7 units on a scale STANDARD_DEVIATION 10.5 | 28.0 units on a scale STANDARD_DEVIATION 12.4 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 27 Participants | 14 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 8 | 33.1 years STANDARD_DEVIATION 9.1 | 35 years STANDARD_DEVIATION 10 |
| Baseline-corrected highest 2-min average pulse rate at the 1st written narrative exposure session | 5.9 beats per minute STANDARD_DEVIATION 4.6 | 6.6 beats per minute STANDARD_DEVIATION 5.3 | 7.2 beats per minute STANDARD_DEVIATION 5.9 |
| Baseline-corrected highest SUDS at the 1st written narrative exposure session | 32.0 units on a scale STANDARD_DEVIATION 18.4 | 33.7 units on a scale STANDARD_DEVIATION 18.1 | 35.3 units on a scale STANDARD_DEVIATION 18.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 7 Participants |
| Region of Enrollment United States | 13 participants | 27 participants | 14 participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 9 / 13 | 9 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
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.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2 | 16.6 score on a scale | Standard Deviation 7.3 |
| Placebo Pill | The Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Score at Week 2 | 17.1 score on a scale | Standard Deviation 12 |
Secondary
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.
Time frame: 1week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | The Baseline-corrected Highest Pulse Rate Across at the Last Written Narrative Exposure Session | 5.3 beats per minute | Standard Deviation 3 |
| Placebo Pill | The Baseline-corrected Highest Pulse Rate Across at the Last Written Narrative Exposure Session | 4.8 beats per minute | Standard Deviation 2.4 |
Secondary
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.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session | 18.9 score on a scale | Standard Deviation 15.8 |
| Placebo Pill | The Baseline-corrected Highest Subjective Unit of Distress Scale (SUDS) Scores at the Last Written Narrative Exposure Session | 40.3 score on a scale | Standard Deviation 22 |