Post-Traumatic Stress Disorders
Conditions
Keywords
PTSD, Sleep disturbance, Eszopiclone, Double-blind, Crossover
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.
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.
Interventions
DRUGEszopiclone
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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Sleep Latency | 8 weeks | Sleep Latency was derived from a subject-completed daily sleep diary. |
| Total Sleep Time | 8 weeks | Total Sleep Time was derived from a subject-completed daily sleep diary. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug vs Placebo 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. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Drug vs Placebo |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 19.0 years STANDARD_DEVIATION 14.3 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Pittsburgh Sleep Quality Index (PSQI)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Pittsburgh Sleep Quality Index (PSQI) | 8.30 units on a scale | Standard Deviation 3.28 |
| Placebo | Pittsburgh Sleep Quality Index (PSQI) | 11.29 units on a scale | Standard Deviation 3.86 |
Primary
Short PTSD Rating Interview (SPRINT)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Short PTSD Rating Interview (SPRINT) | 16.13 units on a scale | Standard Deviation 4.56 |
| Placebo | Short PTSD Rating Interview (SPRINT) | 19.88 units on a scale | Standard Deviation 5.47 |
Secondary
Clinician-Administered PTSD Scale (CAPS)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Clinician-Administered PTSD Scale (CAPS) | 53.92 units on a scale | Standard Deviation 17.05 |
| Placebo | Clinician-Administered PTSD Scale (CAPS) | 67.5 units on a scale | Standard Deviation 20.83 |
Secondary
Sleep Latency
Sleep Latency was derived from a subject-completed daily sleep diary.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Sleep Latency | 25.83 Minutes | Standard Deviation 17.55 |
| Placebo | Sleep Latency | 55.83 Minutes | Standard Deviation 82.39 |
Secondary
Total Sleep Time
Total Sleep Time was derived from a subject-completed daily sleep diary.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Total Sleep Time | 390 Minutes | Standard Deviation 83.46 |
| Placebo | Total Sleep Time | 362.38 Minutes | Standard Deviation 67.3 |