Eszopiclone for Sleep Disturbance and Nightmares in Post-Traumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT00120250
• Recruitment Status: Completed
• First Posted: July 15, 2005
• Results First Posted: February 12, 2014
• Last Update Posted: April 26, 2016
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Mark H. Pollack, Massachusetts General Hospital

Study Description

Brief Summary:

The purpose of this study is to obtain data investigating the safety and efficacy of eszopiclone for the treatment of post-traumatic stress disorder (PTSD)-related sleep disturbance and the impact of improved sleep with eszopiclone treatment on neuroendocrine correlates of PTSD. The investigators hypothesize that eszopiclone will be significantly more effective than placebo and well tolerated for PTSD-related sleep disturbance, improvement in sleep will be associated with improvement in overall PTSD symptoms, and patients with PTSD-related sleep disturbances will have abnormal levels of stress hormones.

Condition or disease	Intervention/treatment	Phase
Post-Traumatic Stress Disorders	Drug: Eszopiclone	Phase 4

Detailed Description:

Post-traumatic stress disorder (PTSD) is characterized by three symptom groupings: re-experiencing symptoms including flashbacks, nightmares, and intrusive memories; physiological hyperarousal; and avoidance symptoms. Of the three major categories of symptoms in PTSD listed by the Diagnostic and Statistical Manual of Mental Disorders, sleep-related problems are listed in two of them: difficulty falling asleep is considered an aspect of hyperarousal symptoms, and nightmares are a type of re-experiencing symptom. Both are found commonly in PTSD. Little is known about the relationship of neuroendocrine dysregulation in PTSD and sleep disturbance. It is possible that successful treatment of sleep disturbance in PTSD may alter an abnormal stress hormone pattern. The novel cyclopyrrolone hypnotic eszopiclone thus presents an intriguing opportunity to examine the treatment of sleep disturbances and nightmares in PTSD. This study will determine the safety, efficacy and impact on neuroendocrine parameters of eszopiclone compared to placebo for sleep disturbance and overall PTSD symptoms in individuals with PTSD and reported sleep disturbance.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Eszopiclone for Sleep Disturbance and Nightmares in Post-Traumatic Stress Disorder
• Study Start Date: June 2005
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eszopiclone; Subjects received 3mg eszopiclone nightly for 3 weeks, followed by a 1 week washout period, followed by 3 weeks of placebo, followed by another 1 week washout.	Drug: Eszopiclone; The total study duration is 8 weeks, with subjects receiving 3mg eszopiclone or placebo nightly for 3 weeks, followed by a 1 week washout period, followed by 3 weeks of the alternate condition, followed by another 1 week washout.; Other Name: Lunesta
Placebo Comparator: Placebo; Subjects received placebo nightly for 3 weeks, followed by a 1 week washout period, followed by 3 weeks of 3mg eszopiclone, followed by another 1 week washout.	Drug: Eszopiclone; The total study duration is 8 weeks, with subjects receiving 3mg eszopiclone or placebo nightly for 3 weeks, followed by a 1 week washout period, followed by 3 weeks of the alternate condition, followed by another 1 week washout.; Other Name: Lunesta

Outcome Measures

Primary Outcome Measures :

1. Short PTSD Rating Interview (SPRINT) [ Time Frame: 8 weeks ]
   The SPRINT is a 8-item, clinician-administered scale assessing core and related symptoms of PTSD. Symptoms are rates on 5 point scales from 0 (not at all) to 4 (very much) where a higher value indicates a worse outcome.
2. Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 8 weeks ]
   The PSQI is a 24-item, patient-administered scale that assess changes in sleep symptomatology. The total PSQI score ranges from 0 to 21 where a higher value indicates a worse sleep symptomatology.

Secondary Outcome Measures :

1. Sleep Latency [ Time Frame: 8 weeks ]
   Sleep Latency was derived from a subject-completed daily sleep diary.
2. Total Sleep Time [ Time Frame: 8 weeks ]
   Total Sleep Time was derived from a subject-completed daily sleep diary.
3. Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Week 3 ]
   The CAPS is a highly detailed measure of the presence and severity of the DSM-IV 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. In this case, the total score for all 17 symptom questions, which is also the sum of the three symptom clusters, is used.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female outpatients 18-64 years of age with a primary diagnosis of PTSD as defined by DSM-IV criteria with associated sleep disturbance

Exclusion Criteria:

• Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception.
• Concurrent use of other psychotropic medications, other than antidepressants at stable dose for at least 4 weeks prior to randomization
• Serious medical illness or instability
• Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood
• Concurrent psychotherapy initiated within one month of randomization or ongoing psychotherapy of any duration directed specifically toward treatment of PTSD and/or sleep disturbance
• Diagnosis of schizophrenia, mental retardation, OCD, organic medical disorders or bipolar disorder, eating disorders in the past 6 months, alcohol or substance abuse in the past 3 months, or dependence within the past 6 months.
• Patients with significant suicidal ideation or who have enacted suicidal behaviors within 6 months prior to intake

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Mark Pollack, M.D.; Massachusetts General Hospital

More Information

Additional Information:

Official Website for the Center for Anxiety and Traumatic Stress Disorders 

Publications of Results:

Pollack MH, Hoge EA, Worthington JJ, Moshier SJ, Wechsler RS, Brandes M, Simon NM. Eszopiclone for the treatment of posttraumatic stress disorder and associated insomnia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Jul;72(7):892-7. doi: 10.4088/JCP.09m05607gry. Epub 2011 Feb 22.

• Responsible Party: Mark H. Pollack, Grainger Professor and Chairman, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00120250
• Other Study ID Numbers: 2005-P-000645
• First Posted: July 15, 2005
• Results First Posted: February 12, 2014
• Last Update Posted: April 26, 2016
• Last Verified: March 2016

Keywords provided by Mark H. Pollack, Massachusetts General Hospital:

PTSD; Sleep disturbance; Eszopiclone; Double-blind; Crossover

Additional relevant MeSH terms:

Dyssomnias; Parasomnias; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases; Eszopiclone; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs