Pimavanserin for Insomnia In Veterans With Posttraumatic Stress Disorder

Study Overview
=================
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.

Official Title
-----------------
Pilot Feasibility Study of Pimavanserin for Insomnia in Veterans With Posttraumatic Stress Disorder

Conditions
-----------------
Post-traumatic Stress Disorder, Insomnia

Intervention / Treatment
-----------------
* Drug: Pimavanserin


Participation Criteria
=================
Eligibility Criteria
-----------------
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 exclusion criteria are still met. Participants identified as having moderate to severe obstructive sleep apnea during the screening polysomnogram. These participants will be referred to clinical treatment Periodic limb movement arousal index 15 or greater or other sleep disorders captured during the screening polysomnogram that may confound, per the opinion of the investigators, the assessment and treatment of insomnia A prolonged QT interval, corrected for heart rate (QTc), at the screening electrocardiogram. A prolonged QTc is defined as 470 milliseconds for males and 480 milliseconds for females. Engagement in an evidence-based psychotherapy for 1-week prior to enrollment that in the opinion of the investigators, may confound the assessment of insomnia Current evidence of clinically significant cardiac, respiratory, gastrointestinal, renal, neurological, hepatic, and/or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments Females who are breastfeeding or pregnant at screening Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically). Current use of a prohibited medications: Hypnotic or sedating medications taken at bedtime for insomnia; antipsychotics and antidepressants with known 5HT2A antagonist activity; medications that increase or decrease the metabolism of pimavanserin; medications that increase the risk of QTc prolongation Patients with conditions known to increase the risk of torsades de pointes and/or sudden death, such as symptomatic bradycardia and other cardiac arrhythmias, uncorrected hypokalemia or hypomagnesemia, and congenital prolongation of the QT interval.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: open-label treatment<br>pimavanserin 34mg at bedtime for 6 weeks | Drug: Pimavanserin<br>* pimavanserin tablet<br>* Other names: Nuplazid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment Rates | The rate of enrollment per month; goal of 6 subjects total | Total duration of recruitment time (5.8 months) | 
| Retention Rates | The number of subjects who complete the protocol in its entirety; goal of 75% of subjects enrolled into treatment | 10 weeks (overall study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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]) | 6 weeks (time between baseline and closeout polysomnogram) | 
| Discontinuation Rates Due to Adverse Effects | The number of subjects who discontinue the protocol due to adverse effects (from either protocol or medication) | 10 weeks (overall study duration) | 
| 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 | 10 weeks (overall study duration) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Post-traumatic Stress Disorder, Insomnia