Complex InsomniaPhase 4PRECEPT-DNCT03937713
Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD
A Phase 4 study testing eszopiclone and Brief behavioral therapy for insomnia in people with Complex Insomnia, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Complex Insomnia
- What is being tested?
- eszopiclone and Brief behavioral therapy for insomnia
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2019to 30 Mar 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Western New York Healthcare System, Buffalo, NY
Buffalo, New York, 14215-1129
About this study
Official title: A Pragmatic Randomized Comparator Trial of Eszopiclone and Brief Behavioral Therapy for Insomnia in CPAP Non Adherent Veterans With PTSD and Complex Insomnia
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.
Read the detailed description
As many as 90% of Veterans with posttraumatic stress disorder (PTSD) report nightmares and insomnia and even when nightmares are excluded, sleep disturbances are the most prevalent symptoms of PTSD with roughly 50%-70% of patients suffering from co-occurring sleep disorders. The typical sleep complaints include nightmares, distressed awakenings, nocturnal panic attacks, sleep terrors and insomnia.
While it has long been established that PTSD engenders sleep disturbances and averse clinical outcomes, current investigations indicate that disordered sleep is also a risk factor for the development of PTSD. In military personnel with combat exposure, comorbid insomnia and OSA, a condition originally labeled as "complex insomnia" has emerged as one of the most challenging sleep disorder to manage. In the presence of PTSD, the co-occurrence of OSA and insomnia is also associated with significant morbidity. Veterans with both PTSD and complex insomnia report more psychiatric symptoms, chronic pain, and higher rates of suicide. Further, these Veterans may have more difficulty adhering to CPAP because of increased awareness of the mask due to frequent awakenings and an inability to initiate or return to sleep with the mask in place. Fortunately, there are effective treatments for each of these sleep disorders. Traditional treatment models consist of treating OSA first, followed by adjunctive or concurrent treatment for insomnia only if the response to CPAP is deemed unsatisfactory. However, the suboptimal response observed in Veterans with PTSD from such an approach in terms of quality of life, PTSD symptoms, and CPAP adherence highlights the need to examine alternative modalities of treatment. At present, there are no general guidelines on the best strategy to treat complex insomnia in Veterans with PTSD. Prior studies have shown that cognitive behavioral therapy (CBT) is effective for treating insomnia when compared with hypnotic agents.Whether combination therapy offers a therapeutic advantage over CBT alone for complex insomnia in Veterans with PTSD is yet to be determined. The objective of this proposal is to conduct a pragmatic, randomized, parallel clinical trial comparing the effectiveness of Brief Behavioral Therapy for Insomnia in Military Veterans (BBTI-MV) plus eszopiclone, a non-benzodiazepine hypnotic, versus BBTI-MV alone in 52 combat-exposed Veterans with PTSD and OSA with coexisting insomnia on global sleep quality of life, PTSD symptoms, and CPAP adherence. The topic addresses several key areas of unmet needs for Veterans with PTSD and sleep disordered breathing. Among these are: 1) the association between complex insomnia and PTSD on global sleep quality of life; and 2) the effectiveness of combined treatment of CBT and eszopiclone versus CBT alone in improving sleep quality and PTSD symptoms; and 3) the impact of each treatment regimen on CPAP adherence. By establishing the most effective therapy in alleviating insomnia that complicates the presence of OSA in Veterans with PTSD, higher CPAP adherence will ultimately translate into improved cognitive function, enhanced quality of life, and suppression of PTSD symptoms. The long term benefit of this trial will also lead to opportunities for more personalized treatment including delivery method via mobile health technologies which will allow greater assimilation of results across several domains.
- Conditions
- Complex Insomnia
- Being tested
- eszopiclone, Brief behavioral therapy for insomnia
- Keywords
- post traumatic stress disorder, complex insomnia, cognitive behavioral therapy, eszopiclone
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eszopicloneDrug
Also called Lunesta
Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomniaBehavioural
Also called BBTI
BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Brief behavioral therapy for insomnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: repeated measures between baseline and 6 months post randomization
Secondary outcomes (3)
Change in PTSD Checklist-5 (PCL-5)
PCL-5 is a 20-item self-report measures that have been widely used in military and civilian population to assess the severity of PTSD symptoms. A total symptom severity score (range 0-80) can be obtained by summing the scores from each of the 20 items that have response options from 0 "not at all" to 4 "extremely". Higher score indicates worse symptoms.
Measured: repeated measures between baseline and 6 months post randomization
Change in Insomnia Severity Index (ISI)
The ISI is a 7-item patient-reported outcome assessing the severity of initial, middle, and late insomnia; sleep satisfaction; interference of insomnia with daytime functioning; noticeability of sleep problems by others; and distress about sleep difficulties. The 5 point scale provides a score ranging from 0 to 28 with higher scores indicating more severe insomnia.
Measured: repeated measures between baseline and 6 months post randomization
Change in Beck Depression Inventory-II (BDI-II)
The BDI-II is a 21-item questionnaire in which respondents indicate on a four-point Likert-type scale (0=minimal to 3=severe) the presence and severity of depressive symptoms during the past 2 weeks. Items are scored on a 4-point scale ranging from 0 to 3, with higher scores indicating the presence of more depressive symptoms. The BDI-score ranges from 0 to 63. Higher scores indicate worse outcomes.
Measured: repeated measures between baseline and 6 months post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start1 Dec 2019
- Primary completion30 Sep 2024
- Study completion30 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Complex InsomniaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ali A El-Solh, MD MPH, Principal investigator, VA Western New York Healthcare System, Buffalo, NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937713
- Sponsor's protocol ID
- NURB-008-18F
- Acronym
- PRECEPT-D
- Status last verified
- Oct 2025
- First submitted
- 1 May 2019
- Last updated
- 21 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Final de-identified data sets will be made available upon specific request and under and authorized DUA. This, in addition to the publications being made available via PubMed Central will enable validation of results by recipients.
Publications
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.
PubMed 40202618
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic Randomized Comparator Trial of Eszopiclone and Brief Behavioral Therapy for Insomnia in CPAP Non Adherent Veterans With PTSD and Complex Insomnia
- ClinicalTrials.gov ID
- NCT03937713
- Acronym / sponsor ID
- PRECEPT-D / NURB-008-18F
- Conditions
- Complex Insomnia
- Keywords
- post traumatic stress disorder, complex insomnia, cognitive behavioral therapy, eszopiclone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Mar 2025 (actual)
- First posted
- 6 May 2019 (actual)
- Results
- Posted 21 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
As many as 90% of Veterans with posttraumatic stress disorder (PTSD) report nightmares and insomnia and even when nightmares are excluded, sleep disturbances are the most prevalent symptoms of PTSD with roughly 50%-70% of patients suffering from co-occurring sleep disorders. The typical sleep complaints include nightmares, distressed awakenings, nocturnal panic attacks, sleep terrors and insomnia.
While it has long been established that PTSD engenders sleep disturbances and averse clinical outcomes, current investigations indicate that disordered sleep is also a risk factor for the development of PTSD. In military personnel with combat exposure, comorbid insomnia and OSA, a condition originally labeled as "complex insomnia" has emerged as one of the most challenging sleep disorder to manage. In the presence of PTSD, the co-occurrence of OSA and insomnia is also associated with significant morbidity. Veterans with both PTSD and complex insomnia report more psychiatric symptoms, chronic pain, and higher rates of suicide. Further, these Veterans may have more difficulty adhering to CPAP because of increased awareness of the mask due to frequent awakenings and an inability to initiate or return to sleep with the mask in place. Fortunately, there are effective treatments for each of these sleep disorders. Traditional treatment models consist of treating OSA first, followed by adjunctive or concurrent treatment for insomnia only if the response to CPAP is deemed unsatisfactory. However, the suboptimal response observed in Veterans with PTSD from such an approach in terms of quality of life, PTSD symptoms, and CPAP adherence highlights the need to examine alternative modalities of treatment. At present, there are no general guidelines on the best strategy to treat complex insomnia in Veterans with PTSD. Prior studies have shown that cognitive behavioral therapy (CBT) is effective for treating insomnia when compared with hypnotic agents.Whether combination therapy offers a therapeutic advantage over CBT alone for complex insomnia in Veterans with PTSD is yet to be determined. The objective of this proposal is to conduct a pragmatic, randomized, parallel clinical trial comparing the effectiveness of Brief Behavioral Therapy for Insomnia in Military Veterans (BBTI-MV) plus eszopiclone, a non-benzodiazepine hypnotic, versus BBTI-MV alone in 52 combat-exposed Veterans with PTSD and OSA with coexisting insomnia on global sleep quality of life, PTSD symptoms, and CPAP adherence. The topic addresses several key areas of unmet needs for Veterans with PTSD and sleep disordered breathing. Among these are: 1) the association between complex insomnia and PTSD on global sleep quality of life; and 2) the effectiveness of combined treatment of CBT and eszopiclone versus CBT alone in improving sleep quality and PTSD symptoms; and 3) the impact of each treatment regimen on CPAP adherence. By establishing the most effective therapy in alleviating insomnia that complicates the presence of OSA in Veterans with PTSD, higher CPAP adherence will ultimately translate into improved cognitive function, enhanced quality of life, and suppression of PTSD symptoms. The long term benefit of this trial will also lead to opportunities for more personalized treatment including delivery method via mobile health technologies which will allow greater assimilation of results across several domains.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| BBTI plus eszopiclone | Experimental | Drug: eszopiclone, Behavioral: Brief behavioral therapy for insomniaparticipants 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. |
| Brief Behavioral Therapy for Insomnia | Active comparator | Behavioral: Brief behavioral therapy for insomniaparticipants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- Insomnia secondary to pain
- History of narcolepsy and/or cataplexy
- Treatment for seizure disorders
- Pregnant or lactating
- History of clinically significant hepatic impairment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eszopicloneAlso: LunestaEszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia | Drug | BBTI plus eszopiclone |
| Brief behavioral therapy for insomniaAlso: BBTIBBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks. | Behavioural | BBTI plus eszopiclone, Brief Behavioral Therapy for Insomnia |
Primary outcome
Change in Pittsburgh Sleep Quality Index (PSQI) (32) at 6 Months Post-randomization
Time frame: repeated measures between baseline and 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.
3 secondary outcomes
Change in PTSD Checklist-5 (PCL-5)
Time frame: repeated measures between baseline and 6 months post randomization
Change in Insomnia Severity Index (ISI)
Time frame: repeated measures between baseline and 6 months post randomization
Change in Beck Depression Inventory-II (BDI-II)
Time frame: repeated measures between baseline and 6 months post randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40202618El-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.
- Individual participant dataSharing planned: Yes. Final de-identified data sets will be made available upon specific request and under and authorized DUA. This, in addition to the publications being made available via PubMed Central will enable validation of results by recipients.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ali A El-Solh, MD MPH principal investigator
VA Western New York Healthcare System, Buffalo, NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing eszopiclone and Brief behavioral therapy for insomnia in people with Complex Insomnia, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pittsburgh Sleep Quality Index (PSQI) (32) at 6 Months Post-randomization (time frame: repeated measures between baseline and 6 months post randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03937713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.