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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

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

Clinicaltrials.gov identifier NCT03937713

Recruitment Status Recruiting

First Posted May 6, 2019

Last update posted October 12, 2020

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:Complex Insomnia
  • Intervention/Treatment: Drug: eszopiclone
    Behavioral: Brief behavioral therapy for insomnia
  • 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
  • Estimated 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.
  • 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: December 2019
  • Estimated Primary Completion Date: October 2023
  • Estimated Study Completion Date: March 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

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.
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.
Outcome Measures
  • Primary Outcome Measures: 1. Change in Pittsburgh Sleep Quality Index (PSQI) (32) [ 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.
  • Secondary Outcome Measures: 1. Change in PTSD checklist-5 (PCL-5) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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
  • Ages Eligible for Study: 18 to 65 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

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
Contacts

Contact: Ali A El-Solh, MD MPH (716) 862-6528 ali.el-solh@va.gov

Contact: Gregory P Beehler, PhD (716) 862-7934 Gregory.Beehler@va.gov

Locations

United States, New York
VA Western New York Healthcare System, Buffalo, NY
Buffalo

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

More Information
  • Responsible Party: VA Office of Research and Development
  • ClinicalTrials.gov Identifier: NCT03937713 History of Changes
  • Other Study ID Numbers: NURB-008-18F
  • First Posted: May 6, 2019 Key Record Dates
  • Last Update Posted: October 12, 2020
  • Last Verified: October 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: 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.
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP)
  • 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
  • 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: post traumatic stress disorder
    complex insomnia
    cognitive behavioral therapy
    eszopiclone
  • Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders