This randomized, double-blind, placebo-controlled trial of doxazosin will assess doxazosin's effectiveness for PTSD nightmares, subjective sleep quality, and non-nightmare PTSD symptoms in adult men and women veterans with full and partial-syndromal PTSD.
This study will involve a randomized, double-blind, placebo-controlled, flexible dose trial of doxazosin (1-10mg) for PTSD nightmares, sleep disturbance and overall PTSD symptoms. The target sample will consist of 60 male and female subjects with chronic PTSD symptoms and prominent nightmares randomly assigned to receive doxazosin (n=30) or placebo (n=30). Participants will be enrolled at the San Francisco VA Medical Center. Following baseline consent procedures, eligibility assessments, and 1-week of baseline assessments including self-report surveys, actigraphy, and at-home EEG (Sleep Profiler), all subjects will initiate doxazosin or equivalently marked placebo at 1mg at bedtime. Subjects will undergo a 4-week titration phase during which doxazosin or placebo may be increased to a maximum dose of 10mg (or equivalently marked placebo) at bedtime based on symptoms and tolerability. After the 4-week titration phase, subjects will continue at stable dose of study medication for a 4-week stable dose phase. Subjects will be asked to complete sleep diaries daily during their participation in the study. In the last week of the stable dose phase, participants will undergo an additional week of at-home sleep monitoring using actigraphy, complete end of treatment surveys, and undergo end-of-treatment clinical assessments and discontinuation of study medication. After discontinuation of study medication, participants will complete three additional days of sleep diaries.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Doxazosin is FDA-approved for the treatment of hypertension and urinary outflow problems associated with benign prostatic hyperplasia. The immediate-release formulation is approved for use from 1mg up to 16mg. Based on drug company information and Micromedex, the SFVA pharmacy on-line reference resource for drug information, the only contraindication to use of doxazosin is hypersensitivity to doxazosin, its contents, or other quinazolines (e.g. prazosin, terazosin).
Placebo, or inactive pill.
San Francisco VA Medical Center
San Francisco, California, United States
Change in Clinician Administered PTSD Scale (CAPS) Distressing Dream Score
For the assessment of nightmares, the CAPS developed for the DSM-IV will be utilized. The CAPS IV's wide use as an outcome measure in clinical research has provided abundant information about its reliability and responsiveness to change with treatment in general and for nightmares specifically. All existing studies of alpha-blockers for PTS nightmares and non-nightmare symptoms have used the CAPS for DSM-IV, and therefore our results will be more comparable to existing studies. The distressing dreams item from the CAPS for DSM-IV also has strong behavioral anchors, providing detail on both the frequency and intensity of nightmares. A CAPS (DSM-IV) distressing dreams item score of \>=3, as used in prior research on alpha-blockers, will be a requirement for inclusion. Change in CAPS distressing dream score between baseline and end-of-treatment will be the primary measure of the reduction of nightmare frequency/intensity.
Time frame: Baseline and Week 9 (end-of-treatment)
Change in Pittsburgh Sleep Quality Index (PSQI)
The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period and acceptable measures of internal homogeneity, consistency (testretest reliability), and validity were obtained. A global PSQI score \> 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
Time frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment)
Change in CAPS PTS Symptom Score
Change in total CAPS score, minus the distressing dreams item score
Time frame: Baseline and Week 9 (end-of-treatment)
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Change in minutes of wake after sleep onset (WASO)
Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.
Time frame: Daily, weeks 0-8
Change in total sleep time (TST)
Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.
Time frame: Daily, weeks 0-8
Change in sleep maintenance (SM)
Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.
Time frame: Daily, weeks 0-8
Nightmare Distress Questionnaire (NDQ)
The NDQ is a self-report assessment of the degree of distress that nightmares cause, and is shown to be a valid, reliable measure of the effects of nightmares.
Time frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment)
PTSD Checklist for DSM- 5 (PCL-5)
The PCL-5 will be used as a secondary measure and to assess the internal consistency of the CAPS PTSD symptom score. The PCL-5 is a validated self-report rating scale for assessing PTSD symptoms. It consists of 20 items that correspond to the DSM-5 symptoms of PTSD.
Time frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment)
Objective measure of change in TST
The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.
Time frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation.
Objective measure of change in WASO
The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.
Time frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation.
Objective measures of change in SM
The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.
Time frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation.