Augmentation Trial of Prazosin for Post-Traumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Placebo-Controlled Augmentation Trial of Prazosin for PTSD

Conditions
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Stress Disorders, Post-Traumatic, Combat Disorders, Sleep Disorders

Intervention / Treatment
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* Drug: prazosin hydrochloride
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: prazosin hydrochloride<br>prazosin Pfizer Minipress oral capsules 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. | Drug: prazosin hydrochloride<br>* 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.<br>* Other names: Pfizer Minipress;|
| Placebo Comparator: placebo<br>placebo oral capsules 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. | Drug: placebo<br>* placebo<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Week 15 | 
| 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. | Baseline to Week 15 | 
| 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. | Change from Baseline to Week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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posttraumatic stress disorder, PTSD, nightmares, prazosin, sleep disturbance, combat trauma