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

Seattle Institute for Biomedical and Clinical Research67 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Stress Disorders, Post-Traumatic Combat Disorders Sleep Disorders

Interventions

prazosin hydrochlorideDRUG

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.

placeboDRUG

placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (2)

VA Puget Sound Health Care System

Seattle, Washington, United States

Madigan Army Medical Center

Tacoma, Washington, United States

Outcomes

Primary Outcomes

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

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

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.