Posttraumatic Stress Disorders
Conditions
Keywords
Post-traumatic stress disorder, sleep disturbance, insomnia, cytokines, anxiety, traumatic event, memory
Brief summary
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.
Interventions
DRUGEszopiclone
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.
DRUGPlacebo
The placebo used in this study looks exactly like eszopiclone but contains no active ingredients.
Sponsors
National Institute of Mental Health (NIMH)
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Symptoms of Post-Traumatic Stress Disorder (PTSD) Between Baseline and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Score on the Pittsburgh Sleep Quality Index With Post-Traumatic Stress Disorder Addendum (PSQI) | Changes in total score between Baseline and Week 12 (range of 0 to 21 worse) | 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 Emotional Bias Memory Encoding Between Baseline and Week 12 | 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. |
| Cytokine Inflammatory Markers | Week 12 | Differences between baseline and week 12 on Interferon-Gamma, Interleukin-βeta, Interleukin-6, Tumor Necrosis Factor-alpha levels between treatment arms (eszopiclone versus placebo). |
| Cytokine Inflammatory Marker on Interleukin-2 | Week 12 | Differences between baseline and week 12 on Interleukin-2 levels between treatment arms (eszopiclone versus placebo). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eszopiclone 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.
Eszopiclone: 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. | 13 |
| Placebo 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.
Placebo: The placebo used in this study looks exactly like eszopiclone but contains no active ingredients. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Eszopiclone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 25 Participants | 13 Participants |
| Region of Enrollment United States | 12 Participants | 25 Participants | 13 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 13 | 9 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Between Baseline and Week 12
Population: Of the 25 subjects that were randomized, 9 did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Change in Symptoms of Post-Traumatic Stress Disorder (PTSD) Between Baseline and Week 12 | -23 units on a scale | Standard Deviation 17.61 |
| Placebo | Change in Symptoms of Post-Traumatic Stress Disorder (PTSD) Between Baseline and Week 12 | -20 units on a scale | Standard Deviation 15.22 |
Secondary
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.
Time frame: Baseline and week 12
Population: Subjects with pre treatment and post treatment emotional bias encoding assessments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Changes in Emotional Bias Memory Encoding Between Baseline and Week 12 | 93 units on a scale | Standard Error 31 |
| Placebo | Changes in Emotional Bias Memory Encoding Between Baseline and Week 12 | 102 units on a scale | Standard Error 32 |
Secondary
Cytokine Inflammatory Marker on Interleukin-2
Differences between baseline and week 12 on Interleukin-2 levels between treatment arms (eszopiclone versus placebo).
Time frame: Week 12
Population: Subjects with baseline and week 12 cytokine assessment of Interleukin-2 IU
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Cytokine Inflammatory Marker on Interleukin-2 | 1.67 IU | Standard Deviation 8 |
| Placebo | Cytokine Inflammatory Marker on Interleukin-2 | -0.07 IU | Standard Deviation 9 |
Secondary
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).
Time frame: Week 12
Population: Subjects with baseline and week 12 cytokine assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone | Cytokine Inflammatory Markers | Interferon-GAMMA pg/mL | 3.62 pg/ml | Standard Deviation 13.98 |
| Eszopiclone | Cytokine Inflammatory Markers | Interleukin-βeta pg/mL | -0.10 pg/ml | Standard Deviation 4 |
| Eszopiclone | Cytokine Inflammatory Markers | Interleukin-6 pg/mL | 1.29 pg/ml | Standard Deviation 8 |
| Eszopiclone | Cytokine Inflammatory Markers | Tumor Necrosis Factor-alpha pg/mL | 67.27 pg/ml | Standard Deviation 11 |
| Placebo | Cytokine Inflammatory Markers | Tumor Necrosis Factor-alpha pg/mL | 64.80 pg/ml | Standard Deviation 10 |
| Placebo | Cytokine Inflammatory Markers | Interferon-GAMMA pg/mL | -1.55 pg/ml | Standard Deviation 6.35 |
| Placebo | Cytokine Inflammatory Markers | Interleukin-6 pg/mL | -0.08 pg/ml | Standard Deviation 9 |
| Placebo | Cytokine Inflammatory Markers | Interleukin-βeta pg/mL | 0.30 pg/ml | Standard Deviation 7 |
Secondary
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).
Time frame: Changes in total score between Baseline and Week 12 (range of 0 to 21 worse)
Population: Of the 25 subjects that were randomized, 9 did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Total Score on the Pittsburgh Sleep Quality Index With Post-Traumatic Stress Disorder Addendum (PSQI) | -4.13 units on a scale | Standard Deviation 2.93 |
| Placebo | Total Score on the Pittsburgh Sleep Quality Index With Post-Traumatic Stress Disorder Addendum (PSQI) | -3.33 units on a scale | Standard Deviation 3.59 |