PRECEPT-D: Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD

Sponsor
VA Office of Research and Development (U.S. Fed)
Overall Status
Recruiting
CT.gov ID
NCT03937713
Collaborator
(none)
52
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2
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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

Study Type:
Interventional
Anticipated Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention 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.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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 1, 2019
Anticipated Primary Completion Date :
Oct 30, 2023
Anticipated Study Completion Date :
Mar 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: BBTI plus eszopiclone

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
Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Other Names:
  • Lunesta
  • Behavioral: Brief behavioral therapy for insomnia
    BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
    Other Names:
  • BBTI
  • Active Comparator: BBTI

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

    Behavioral: Brief behavioral therapy for insomnia
    BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
    Other Names:
  • BBTI
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Pittsburgh Sleep Quality Index (PSQI) (32) [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.

    Secondary Outcome Measures

    1. Change in PTSD checklist-5 (PCL-5) [repeated measures between baseline and 6 months post randomization]

      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.

    2. Change in Insomnia Severity Index (ISI) [repeated measures between baseline and 6 months post randomization]

      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.

    3. Change in Beck Depression Inventory-II (BDI-II) [repeated measures between baseline and 6 months post randomization]

      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.

    Other Outcome Measures

    1. CPAP adherence [repeated measures between baseline and 6 months post randomization]

      CPAP adherence will be obtained by downloading the data stored on the SmartCard. CPAP adherence will be defined as the percentage use of CPAP for 4h/night during a 28 consecutive day period. Poor adherence is denoted by <70% use of more than 4 hours per night

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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

    Exclusion Criteria:
    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 VA Western New York Healthcare System, Buffalo, NY Buffalo New York United States 14215

    Sponsors and Collaborators

    • VA Office of Research and Development

    Investigators

    • Principal Investigator: Ali A El-Solh, MD MPH, VA Western New York Healthcare System, Buffalo, NY

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    VA Office of Research and Development
    ClinicalTrials.gov Identifier:
    NCT03937713
    Other Study ID Numbers:
    • NURB-008-18F
    First Posted:
    May 6, 2019
    Last Update Posted:
    Mar 7, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by VA Office of Research and Development
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 7, 2022