Eszopiclone for the Treatment of Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine if eszopiclone relative to placebo (sugar pill) is effective and tolerable for people with posttraumatic stress disorder (PTSD)-related sleep disturbance. The investigators will also examine the impact of treatment on sleep patterns, memory recall bias, and level of inflammatory markers (cytokines). The investigators predict eszopiclone will lead to greater improvement than placebo in measures of PTSD symptoms, memory recall bias, and level of inflammatory markers.

Official Title
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Eszopiclone for the Treatment of PTSD

Conditions
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Posttraumatic Stress Disorders

Intervention / Treatment
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* Drug: Eszopiclone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients age 18-65 with a primary diagnosis of PTSD and associated sleep disturbance Good physical health Willingness and ability to comply with the requirements of the study protocol Exclusion Criteria: Women pregnant, lactating, or of childbearing potential not using medically accepted contraception Concurrent use of other psychotropic medications at least two weeks prior to baseline Concurrent use of other anti-inflammatory medications or anti-cytokine medications. If used on an as-needed (PRN) basis, subjects may enter the study, but will be excluded from cytokine analyses Concurrent use of beta-blockers less than one month prior to baseline Serious medical illness or instability for which hospitalization may be likely within the next year Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood Sleep apnea or restless leg syndrome Concurrent psychotherapy initiated within 3 months of randomization or ongoing psychotherapy of any duration directed specifically toward treatment of PTSD and/or sleep disturbance Patients with significant suicidal ideation Current legal actions related to trauma or an ongoing relationship with assailant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eszopiclone<br>The total study duration is 16 weeks, with subjects taking 3mg eszopiclone at bedtime for 12 weeks. There is one follow-up visit after the 12 week treatment phase. | Drug: Eszopiclone<br>* Eszopiclone has been approved by the US Food and Drug Administration (FDA) for the treatment of insomnia (inability to sleep). Eszopiclone has not been specifically approved by the FDA for people who have PTSD-related sleep disturbance.<br>* Other names: Lunesta®;|
| Placebo Comparator: Placebo<br>The total study duration is 16 weeks, with subjects taking placebo at bedtime for 12 weeks. There is one follow-up visit after the 12 week treatment phase. | Drug: Placebo<br>* The placebo used in this study looks exactly like eszopiclone but contains no active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Symptoms of Post-Traumatic Stress Disorder (PTSD) Between Baseline and Week 12 | The Clinician-Administered PTSD Scale (CAPS) is a highly detailed measure of the presence and severity of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-IV) Post-Traumatic Stress Disorder (PTSD) criteria. The severity score was calculated by adding up the frequency score (scale 0 = none of the time to 4 = most or all of the time) and an intensity score (scale 0 = none to 4 = extreme), which can then be summed for all 17 symptom questions and/or for the three symptom clusters. Scores range from 0 to 136, where greater than or equal to 80 represents extreme PTSD symptomatology. | Between Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Score on the Pittsburgh Sleep Quality Index With Post-Traumatic Stress Disorder Addendum (PSQI) | This standard daily sleep diary addresses timing of sleep, ability to fall and stay asleep, dreams, nightmares, and factors which can affect sleep (e.g. caffeine). It requires a summary of the subscales: Duration of sleep + Sleep Disturbance + Sleep Latency + Days of dysfunction due to sleepiness + Sleep efficiency + Overall Sleep Quality + Needing medication to sleep. All subscales are measured from 0 to 3 (Minimum Score = 0 better; Maximum Score = 3 worse). The Minimum TOTAL Score is 0 (better) and Maximum TOTAL Score is 21 (worse). | Changes in total score between Baseline and Week 12 (range of 0 to 21 worse) | 
| Changes in Emotional Bias Memory Encoding Between Baseline and Week 12 | Changes in Emotional Bias Memory Encoding by measuring mean hits minus the false alarms at baseline and at week 12. Subjects perform an encoding session on the 1st day utilizing 147 picture slides, thirty six pictures with negative valence, 36 with neutral valence and additional 75 pictures randomly intermixed. Higher false alarms are associated with lower emotional bias memory encoding. | Baseline and week 12 | 
| Cytokine Inflammatory Markers | Differences between baseline and week 12 on Interferon-Gamma, Interleukin-βeta, Interleukin-6, Tumor Necrosis Factor-alpha levels between treatment arms (eszopiclone versus placebo). | Week 12 | 
| Cytokine Inflammatory Marker on Interleukin-2 | Differences between baseline and week 12 on Interleukin-2 levels between treatment arms (eszopiclone versus placebo). | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-traumatic stress disorder, sleep disturbance, insomnia, cytokines, anxiety, traumatic event, memory