Pimavanserin for Insomnia in Veterans With PTSD

NCT05441280 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MHBP-001-21FIK2CX002363-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a preliminary randomized, double-blind, placebo-controlled trial comparing pimavanserin 34mg at bedtime vs. placebo for the treatment of insomnia associated with post-traumatic stress disorder.

Conditions

Post-traumatic Stress Disorder; Insomnia

Keywords

Stress Disorders, Post-Traumatic; Sleep Initiation and Maintenance Disorders

Outcome Measures

Primary Outcomes (1)

• Insomnia Severity Index (ISI)

  Mean change in ISI total score at 8-weeks in active vs. placebo groups

  8 weeks post-randomization

Secondary Outcomes (2)

• Pittsburgh Sleep Quality Index (PSQI)

  8 weeks post-randomization

• PTSD Checklist for DSM-5

  8 weeks post-randomization

Study Arms (2)

Pimavanserin 34mg PO at bedtime

ACTIVE COMPARATOR

Pimavanserin 34mg is taken by mouth at bedtime for 8 weeks .

Drug: pimavanserin

Placebo PO at bedtime

PLACEBO COMPARATOR

The active study medication listed above will be compared with a placebo, which is a pill that looks like a study medication but has no medication in it

Other: Placebo

Interventions

pimavanserin DRUG

pimavanserin 34mg PO at bedtime

Also known as: Nuplazid

Pimavanserin 34mg PO at bedtime

Placebo OTHER

The placebo is a pill that looks like a study medication but has no medication in it

Placebo PO at bedtime

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult, male and female Veterans, aged 18-64;
• At the initial enrollment visit, meets DSM-5 standards of chronic insomnia disorder, as follows:
• 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;
• Insomnia frequency of 3 times per week
• The duration of the insomnia complaint is 3 months
• Associated with complaint of daytime impairment;
• Insomnia Severity Index (ISI) total score 15 (moderate insomnia);
• Determined to have clinically significant PTSD symptoms as per the PTSD Checklist (PCL-5); a total score of 33 is a recommended cutoff for a diagnosis of PTSD;
• Willing and able to comply with all aspects of the protocol;
• Willing to not start a concurrent behavioral or other treatment program for insomnia, PTSD, or other psychiatric disorders during the participation in the study;
• It is required that women of child-bearing potential who are sexually active agree to either refrain from sexual activity or use a method of contraception for the duration of the study (i.e., beginning 30 days prior to drug initiation and extending to 30 days after the last dose of study drug). Acceptable methods of contraception include: 1) hormonal contraceptives (e.g., oral contraceptives, injectable contraceptives, contraceptive implant) or a non-hormonal intrauterine device;
• Subjects are permitted to remain on serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, anticonvulsants (excluding strong CYP3A4 inhibitors or inducers), and other non-prohibited, psychiatric medications taken at stable doses for at least 1 month prior to study entry.

You may not qualify if:

• 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 cannabis 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 (e.g., caffeinated beverages consumed after 18:00 3 times/week 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 sleep 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 apnea hypopnea index equal to or greater than 15 on home sleep test or attended polysomnography);
• 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 5, or STOP score of 2 plus (body mass index \> 35 kg/m2 or male or neck circumference \>40 cm), are considered to be high risk and will be referred to clinical treatment;
• Participants identified as having an apnea hypopnea index (AHI) 15 during the screening polysomnogram. These participants will be referred to clinical treatment;
• Periodic limb movement arousal index 15 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 CBT-I, prolonged exposure or cognitive processing therapy for 1-week prior to enrollment that in the opinion of the investigators may confound the assessment of insomnia and/or PTSD;
• Current evidence of clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic, neurological, or other medical illness 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;

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Sleep Initiation and Maintenance Disorders

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Melissa B Jones, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa B Jones, MD

CONTACT

(713) 794-1414; Melissa.Jones10@va.gov

Ricardo E Jorge, MD

CONTACT

(713) 791-1414; Ricardo.Jorge@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double (participant, investigator)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Pimavanserin 34mg at bedtime

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 1, 2022
• Study Start: December 28, 2023
• Primary Completion (Estimated): July 12, 2027
• Study Completion (Estimated): July 12, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)