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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00120250
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.7

Study Details

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
• 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: Jun 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 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 Names: 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 Names: Lunesta

Outcome Measures

Primary Outcome Measures

1. Short PTSD Rating Interview (SPRINT) [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) [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 [8 weeks]

   Sleep Latency was derived from a subject-completed daily sleep diary.

2. Total Sleep Time [8 weeks]

   Total Sleep Time was derived from a subject-completed daily sleep diary.

3. Clinician-Administered PTSD Scale (CAPS) [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Official Website for the Center for Anxiety and Traumatic Stress Disorders

Publications

None provided.

• 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: Jul 15, 2005
• Last Update Posted: Apr 26, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Mark H. Pollack, Grainger Professor and Chairman, Massachusetts General Hospital: PTSD; Sleep disturbance; Eszopiclone; Double-blind; Crossover
• Additional relevant MeSH terms: Dyssomnias; Parasomnias; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Eszopiclone

Study Results

Participant Flow

Arm/Group Title	Eszopiclone, Then Placebo	Placebo, Then Eszopiclone
Arm/Group Description	The total study duration is 8 weeks, with subjects receiving 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.	The total study duration is 8 weeks, with subjects receiving 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.
Period Title: Overall Study
STARTED	13	14
COMPLETED	12	12
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Drug vs Placebo
Arm/Group Description	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.
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.0 (14.3)
Sex: Female, Male (Count of Participants)
Female	17 70.8%
Male	7 29.2%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Short PTSD Rating Interview (SPRINT)
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	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.	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.
Measure Participants	24	24
Mean (Standard Deviation) [units on a scale]	16.13 (4.56)	19.88 (5.47)

2. Primary Outcome

Title	Pittsburgh Sleep Quality Index (PSQI)
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	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.	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.
Measure Participants	24	24
Mean (Standard Deviation) [units on a scale]	8.30 (3.28)	11.29 (3.86)

3. Secondary Outcome

Title	Sleep Latency
Description	Sleep Latency was derived from a subject-completed daily sleep diary.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	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.	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.
Measure Participants	24	24
Mean (Standard Deviation) [Minutes]	25.83 (17.55)	55.83 (82.39)

4. Secondary Outcome

Title	Total Sleep Time
Description	Total Sleep Time was derived from a subject-completed daily sleep diary.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	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.	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.
Measure Participants	24	24
Mean (Standard Deviation) [Minutes]	390 (83.46)	362.38 (67.3)

5. Secondary Outcome

Title	Clinician-Administered PTSD Scale (CAPS)
Description	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.
Time Frame	Week 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	The total study duration is 8 weeks, with subjects receiving 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.	The total study duration is 8 weeks, with subjects receiving 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.
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	53.92 (17.05)	67.5 (20.83)

Adverse Events

Arm/Group Title	Drug vs Placebo
Arm/Group Description	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.
All Cause Mortality
	Drug vs Placebo
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Drug vs Placebo
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	Drug vs Placebo
	Affected / at Risk (%)	# Events
Total	0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.