Stress Disorders, Post-Traumatic, Combat Disorders, Sleep Disorders
Conditions
Keywords
posttraumatic stress disorder, PTSD, nightmares, prazosin, sleep disturbance, combat trauma
Brief summary
The purpose of this study is to determine whether prazosin will: * reduce the incidence of nightmares and sleep disturbance * increase functioning and sense of well being in combat-trauma exposed Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans.
Detailed description
This is a 15-week randomized parallel design, double-blind, placebo-controlled augmentation trial of prazosin to evaluate the efficacy and tolerability of prazosin augmentation in the treatment of PTSD trauma-related nightmares, sleep disturbance, global function and sense of well-being, and other clinical features and comorbidities of PTSD. Participants will be 210 OIF/OEF soldiers and veterans who have suffered war zone trauma. Participants will be randomized 1:1 to prazosin or placebo and all previous psychotropic medications and/or psychotherapy will be maintained constant. Randomization will be stratified by site and use of an antidepressant.
Interventions
Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized first dose effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.
DRUGplacebo
placebo
Sponsors
United States Department of Defense
VA Puget Sound Health Care System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Seattle Institute for Biomedical and Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years; * Clear evidence of exposure to one or more war zone trauma events sufficient to satisfy DSM-IV criterion A1 for diagnosis of PTSD; * DSM-IV diagnosis of PTSD derived from the CAPS; CAPS total score \>50; * CAPS Recurrent Distressing Dreams item score \>5 (of maximum score of 8); * stable dose of non-exclusionary medications and psychotherapeutic treatment for at least 4 weeks prior to randomization; * good general medical health. * Female participants must agree to use a reliable form of birth control during the study.
Exclusion criteria
* Psychiatric/Behavioral - meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder, delirium, or any DSM-IV cognitive disorder; substance dependence disorder within 3 months or any current substance dependence; current cocaine or stimulant abuse; severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others. * Medical - acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension or orthostatic hypotension, chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy, or diagnosed sleep apnea; allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item | Baseline to Week 15 | Item B-2 recurrent distressing dreams of the event is a single item from the Clinician Administered PTSD Scale. The rating consists of two parts: Frequency and Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 15. |
| Change in Pittsburgh Sleep Quality Index (PSQI) | Baseline to Week 15 | Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 15. |
| Clinical Global Impression of Change (CGIC) | Change from Baseline to Week 15 | The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The CGIC is used to determine the impact of treat effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measures the proportion of responders who were rated markedly or moderately improved at Week 15 compared to Baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prazosin Hydrochloride prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized first dose effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually. | 32 |
| Placebo placebo: placebo titrated in the same manner as prazosin arm. | 35 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | opted for open label prazosin | 1 | 1 |
| Overall Study | planned major surgery | 0 | 1 |
| Overall Study | relocation/deployment | 4 | 1 |
| Overall Study | scheduling conflicts | 0 | 2 |
| Overall Study | started exclusionary medication | 0 | 1 |
| Overall Study | too busy to continue | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Prazosin Hydrochloride | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 6.6 | 30.8 years STANDARD_DEVIATION 6.5 | 30.4 years STANDARD_DEVIATION 6.5 |
| Region of Enrollment United States | 32 participants | 35 participants | 67 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 26 Participants | 31 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 32 | 25 / 35 |
| serious Total, serious adverse events | 0 / 32 | 2 / 35 |
Outcome results
Primary
Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item
Item B-2 recurrent distressing dreams of the event is a single item from the Clinician Administered PTSD Scale. The rating consists of two parts: Frequency and Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 15.
Time frame: Baseline to Week 15
Population: Of the 67 subjects randomized, 46 completed the full 15 weeks (23 per group). The outcome data reports only those 46 participants who completed the full 15 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin Hydrochloride | Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item | 3.1 Scores on a Scale | Standard Error 0.3 |
| Placebo | Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item | 1.2 Scores on a Scale | Standard Error 0.3 |
Primary
Change in Pittsburgh Sleep Quality Index (PSQI)
Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 15.
Time frame: Baseline to Week 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin Hydrochloride | Change in Pittsburgh Sleep Quality Index (PSQI) | 5.6 Scores on a Scale | Standard Error 0.7 |
| Placebo | Change in Pittsburgh Sleep Quality Index (PSQI) | 2.8 Scores on a Scale | Standard Error 0.6 |
Primary
Clinical Global Impression of Change (CGIC)
The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The CGIC is used to determine the impact of treat effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measures the proportion of responders who were rated markedly or moderately improved at Week 15 compared to Baseline.
Time frame: Change from Baseline to Week 15
Population: Of the 67 subjects randomized, 46 completed the full 15 weeks (23 per group). The outcome data reports only those 46 participants who completed the full 15 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prazosin Hydrochloride | Clinical Global Impression of Change (CGIC) | 64 Percentage of responders |
| Placebo | Clinical Global Impression of Change (CGIC) | 27 Percentage of responders |