Clinical trial NCT03937713: Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Complex Insomnia
Keywords: post traumatic stress disorder
complex insomnia
cognitive behavioral therapy
eszopiclone
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2019-05-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in Pittsburgh Sleep Quality Index (PSQI) (32)
timeFrame: repeated measures between baseline and 6 months post randomization
Secondary outcomes:
measure: Change in PTSD checklist-5 (PCL-5)
timeFrame: repeated measures between baseline and 6 months post randomization
measure: Change in Insomnia Severity Index (ISI)
timeFrame: repeated measures between baseline and 6 months post randomization
measure: Change in Beck Depression Inventory-II (BDI-II)
timeFrame: repeated measures between baseline and 6 months post randomization
Other outcomes:
measure: CPAP adherence
timeFrame: repeated measures between baseline and 6 months post randomization
Locations:
city: Buffalo
country: United States
facility: VA Western New York Healthcare System, Buffalo, NY
state: New York
Study officials:
affiliation: VA Western New York Healthcare System, Buffalo, NY
name: Ali A El-Solh, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: