Insomnia, Post-traumatic Stress Disorder
Conditions
Keywords
Post-traumatic Stress Disorder, Insomnia
Brief summary
This preliminary, open-label study assesses the feasibility of 34mg at bedtime for 6 weeks in Veterans with Posttraumatic Stress Disorder and insomnia.
Detailed description
More treatments are needed to target insomnia in Veterans with Posttraumatic Stress Disorder. There is evidence to suggest that pimavanserin, a medication approved by the Food and Drug Administration for the treatment of psychosis in Parkinson's disease, may improve deep sleep and insomnia. This study preliminary assesses the feasibility of pimavanserin 34mg at bedtime for 6 weeks for the treatment of chronic insomnia in Veterans with Posttraumatic Stress Disorder.
Interventions
DRUGPimavanserin
pimavanserin tablet
Sponsors
Baylor College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Meets criteria for current Posttraumatic Stress Disorder (PTSD), as per a total score of ≥33 on the PTSD Checklist (PCL-5) and Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for PTSD. * Meets DSM-5 standards of chronic insomnia disorder, as follows: a. Complains of dissatisfaction with nighttime sleep in the form of difficulty falling asleep (subjective sleep onset latency ≥30 minutes), difficulty staying asleep (subjective time awake after sleep onset ≥30 minutes), and/or awakening earlier in the morning (≥30 minutes before scheduled wake time and before a total sleep time of 6.5 hours) than desired. b. Insomnia frequency of ≥3 times per week c. The duration of the insomnia complaint is ≥3 months d. Associated with complaint of daytime impairment. * Insomnia Severity Index total score ≥15 (moderate insomnia). * Willing to not start a concurrent behavioral or other treatment program for insomnia, PTSD, or other psychiatric disorders during the participation in the study. * Women of child-bearing potential who are sexually active agree to use two methods of contraception for the duration of the study and extending to 30 days after the last dose of study drug.
Exclusion criteria
* Current or a history of a primary psychotic disorder (i.e., schizophrenia, schizoaffective or bipolar disorder) * Active suicidal or homicidal ideation requiring crisis intervention * Current moderate or severe alcohol or marijuana use disorder, or other illicit use disorder of any severity * A history of moderate or severe traumatic brain injury or other neurological illness (i.e., stroke, epilepsy, multiple sclerosis); * Caffeine use that is deemed excessive and is contributing to the insomnia per the opinion of the investigators (i.e. caffeinated beverages consumed after 18:00 3 times/week or more and/or that correlates with the timing of the insomnia complaints). * Tobacco use before bedtime that is contributing to the insomnia per the opinion of the investigators or that would interfere with completing an overnight polysomnogram. * Previous diagnosis of periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, narcolepsy, Rapid Eye Movement Behavior Disorder, or other sleep disorders (except obstructive sleep apnea) that may confound, per the opinion of the investigators, the assessment of insomnia. * Previous diagnosis of moderate to severe obstructive sleep apnea (defined as an AHI equal to or greater than 15) * Participants deemed to be at high risk of moderate to severe obstructive sleep apnea per the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and male Gender questionnaire (STOP-BANG). Subjects with a STOP-BANG score of 5 or greater, or STOP score of 2 or greater plus body mass index greater than 35 kg/m2 or male or neck circumference greater than 40 cm, are considered to be high-risk. These participants can re-enter the study following adherence to therapy for 1-month and if inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment Rates | Total duration of recruitment time (5.8 months) | The rate of enrollment per month; goal of 6 subjects total |
| Retention Rates | 10 weeks (overall study) | The number of subjects who complete the protocol in its entirety; goal of 75% of subjects enrolled into treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Duration of Stage N3 Sleep Pre- and Post-treatment | 6 weeks (time between baseline and closeout polysomnogram) | The mean difference in duration of stage N3 sleep from baseline polysomnogram to week-6 polysomnogram (\[Time in N3 post-treatment\] - \[Time in N3 at baseline polysomnogram\]) |
| Discontinuation Rates Due to Adverse Effects | 10 weeks (overall study duration) | The number of subjects who discontinue the protocol due to adverse effects (from either protocol or medication) |
| Completion Rates of Key Outcome Measures | 10 weeks (overall study duration) | The percentage of participants who complete subject and objective measures of insomnia, including sleep diaries, actigraphy, and attended polysomnography |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from clinics and clinician referrals at the Michael E. DeBakey VA Medical Center
Pre-assignment details
Pre-assignment exclusions (n=5): non-adherent to CPAP (n=2), bradycardia and hepatic dysfunction (n=1), psychosis (n=1), lost to follow up (n=1)
Participants by arm
| Arm | Count |
|---|---|
| Open-label Treatment pimavanserin 34mg at bedtime for 6 weeks
Pimavanserin: pimavanserin tablet | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Open-label Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 35.33 years STANDARD_DEVIATION 6.35 |
| Current depressive disorder | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Recruitment Rates
The rate of enrollment per month; goal of 6 subjects total
Time frame: Total duration of recruitment time (5.8 months)
Population: Subjects enrolled into open label treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Treatment | Recruitment Rates | 1.03 participants enrolled per month |
Comparison: Recruitment goal of 6 subjects total.95% CI: [0.38, 2.25]
Primary
Retention Rates
The number of subjects who complete the protocol in its entirety; goal of 75% of subjects enrolled into treatment
Time frame: 10 weeks (overall study)
Population: Subjects enrolled into open-label treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Treatment | Retention Rates | 6 Participants |
Comparison: Binary outcome (completed protocol yes vs. no); goal of 75% of subjects completing protocol95% CI: [0.54, 1]
Secondary
Completion Rates of Key Outcome Measures
The percentage of participants who complete subject and objective measures of insomnia, including sleep diaries, actigraphy, and attended polysomnography
Time frame: 10 weeks (overall study duration)
Population: Subjects enrolled into open-label treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Treatment | Completion Rates of Key Outcome Measures | Completed sleep study 1 | 6 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | Completed sleep study 2 | 6 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | Completed sleep study 3 | 5 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | At least 4 days of actigraphy pre-treatment | 6 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | At least 4 days of actigraphy post-treatment | 6 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | At least 4 days of sleep diary pre-treatment | 6 Participants |
| Open-label Treatment | Completion Rates of Key Outcome Measures | At least 4 days of sleep diary post-treatment | 6 Participants |
Comparison: Binary outcome: Completed sleep study 1 yes vs. no95% CI: [0.54, 1]
Comparison: Binary outcome: completed sleep study 2 yes vs. no95% CI: [0.54, 1]
Comparison: Binary outcome: completed sleep study 3 yes vs. no95% CI: [0.36, 0.996]
Comparison: Binary outcome: at least 4 days of actigraphy data pre-treatment yes vs. no95% CI: [0.54, 1]
Comparison: Binary outcome: at least 4 days of actigraphy post-treatment yes vs. no95% CI: [0.54, 1]
Comparison: Binary outcome: at least 4 days of sleep diary pre-treatment yes vs. no95% CI: [0.54, 1]
Comparison: Binary outcome: at least 4 days of sleep diary post-treatment yes vs. no95% CI: [0.54, 1]
Secondary
Discontinuation Rates Due to Adverse Effects
The number of subjects who discontinue the protocol due to adverse effects (from either protocol or medication)
Time frame: 10 weeks (overall study duration)
Population: Number of subjects enrolled into open-label treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Treatment | Discontinuation Rates Due to Adverse Effects | 0 Participants |
Comparison: Binary outcome: Discontinued due to adverse effects yes vs. no95% CI: [0, 0.46]
Secondary
Mean Change in Duration of Stage N3 Sleep Pre- and Post-treatment
The mean difference in duration of stage N3 sleep from baseline polysomnogram to week-6 polysomnogram (\[Time in N3 post-treatment\] - \[Time in N3 at baseline polysomnogram\])
Time frame: 6 weeks (time between baseline and closeout polysomnogram)
Population: Subjects enrolled in open-label treatment and completed baseline and post-treatment polysomnogram (1 subject could not complete post-treatment polysomnogram due to pandemic).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Treatment | Mean Change in Duration of Stage N3 Sleep Pre- and Post-treatment | 21.7 minutes | Standard Deviation 39.57 |
Comparison: alternative hypothesis: true difference in means is not equal to 0p-value: 0.287395% CI: [-27.4, 70.8]t-test, 2 sided