Pimavanserin for Insomnia In Veterans With Posttraumatic Stress Disorder
Condition: Post-traumatic Stress Disorder; Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Pimavanserin
Intervention description: pimavanserin tablet
Intervention MeSH terms: Pimavanserin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Post-traumatic Stress Disorder; Insomnia

Summary:

      This preliminary, open-label study assesses the feasibility of 34mg at bedtime for 6 weeks in
      Veterans with Posttraumatic Stress Disorder and insomnia.
    

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.