Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD

NCT03937713 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: NURB-008-18F
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (OSA) is commonly reported in Veterans with post-traumatic stress disorder, which can potentiate symptoms of anxiety and depression, daytime symptoms and worsen nightmares. Continuous positive airway pressure (CPAP) is the most effective therapy but adherence to treatment is suboptimal. Insomnia is considered a barrier to long-term adherence. The overarching theme of the proposal is to compare the effectiveness of cognitive behavioral therapy for insomnia (CBT) plus eszopiclone, a nonbenzodiazepine hypnotic, versus CBT alone in Veterans with PTSD who are diagnosed with both OSA and insomnia, using a randomized, clinical trial, on sleep quality of life, PTSD severity, and CPAP adherence.

Conditions

Complex Insomnia

Keywords

post traumatic stress disorder; complex insomnia; cognitive behavioral therapy; eszopiclone

Outcome Measures

Primary Outcomes (1)

• Change in Pittsburgh Sleep Quality Index (PSQI) (32) at 6 Months Post-randomization

  The Pittsburgh Sleep Quality Index is a 19-item, self-rated questionnaire, assessed various aspects of sleep, sleep quality, and sleep disturbances. The PSQI is composed of 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score. An overall score ranges from 0 to 21, where lower scores denote a healthier sleep quality.

  repeated measures between baseline and 6 months post randomization

Secondary Outcomes (3)

• Change in PTSD Checklist-5 (PCL-5)

  repeated measures between baseline and 6 months post randomization

• Change in Insomnia Severity Index (ISI)

  repeated measures between baseline and 6 months post randomization

• Change in Beck Depression Inventory-II (BDI-II)

  repeated measures between baseline and 6 months post randomization

Other Outcomes (1)

• CPAP Adherence

  repeated measures between baseline and 6 months post randomization

Study Arms (2)

BBTI plus eszopiclone

EXPERIMENTAL

participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.

Drug: eszopiclone; Behavioral: Brief behavioral therapy for insomnia

Brief Behavioral Therapy for Insomnia

ACTIVE COMPARATOR

participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.

Behavioral: Brief behavioral therapy for insomnia

Interventions

eszopiclone DRUG

Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia

Also known as: Lunesta

BBTI plus eszopiclone

Brief behavioral therapy for insomnia BEHAVIORAL

BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.

Also known as: BBTI

BBTI plus eszopiclone; Brief Behavioral Therapy for Insomnia

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years and \<65 years old
• Diagnosis of PTSD as determined by the intake conducted through the PTSD Clinic or the Mental Health Clinic
• Documented obstructive sleep apnea by polysomnography (AHI 5 or more/hour) who are non-adherent to CPAP as defined by device usage of less than 4 hours per night
• Chronic ( 3 months' duration) insomnia disorder
• Psychotherapeutic treatment stable for at least 4 weeks prior to randomization
• Capable of giving informed consent

You may not qualify if:

• Insomnia secondary to pain
• History of narcolepsy and/or cataplexy
• Treatment for seizure disorders
• Pregnant or lactating
• History of clinically significant hepatic impairment
• History of hypersensitivity, intolerance, or contraindication to eszopiclone
• Use of potent cytochrome p450 3A4 inhibitor medications (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) and is unwilling or it is clinically contraindicated to stop the medication
• Unwilling to try or use CPAP
• Diagnosis of current schizophrenia or schizoaffective disorder
• Diagnosis of a substance dependence/abuse disorder in the past year
• History of complex nocturnal behaviors while using eszopiclone
• Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others
• Diagnosis of bipolar disorder
• Consumption of more than two alcoholic beverages per night
• Documented or self-reported resolution of insomnia from current behavioral or pharmacological treatment of insomnia

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Western New York Healthcare System, Buffalo, NY

Buffalo, New York, 14215-1129, United States

Location

Related Publications (1)

• El-Solh AA, Lawson Y, Martinson A, Wilding G. Cognitive Behavioral Therapy Alone or in Combination with Eszopiclone in Comorbid Insomnia and Obstructive Sleep Apnea in Veterans with Posttraumatic Stress Disorder: A Randomized Trial. Psychiatr Q. 2025 Dec;96(4):787-802. doi: 10.1007/s11126-025-10143-9. Epub 2025 Apr 9.

  PMID: 40202618 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Eszopiclone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Pyridines

Results Point of Contact

• Title: Associate Chief of Staff for Research
• Organization: VA ORD

ali.el-solh@va.gov

716-862-6528

Study Officials

• Ali A El-Solh, MD MPH

  VA Western New York Healthcare System, Buffalo, NY

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: A randomized comparator 1:1 to explore the comparative effectiveness of combination treatment of behavioral and pharmacological interventions with behavioral therapy alone in improving sleep quality of life, Veterans with PTSD and complex insomnia.

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 6, 2019
• Study Start: December 1, 2019
• Primary Completion: September 30, 2024
• Study Completion: March 30, 2025
• Last Updated: October 21, 2025
• Results First Posted: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The de-identified data will be available after the primary manuscript is published
• Access Criteria: The de-identified data will be available after the primary manuscript is published for a period of 6 years

Locations

US (1)