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Sponsors and Collaborators: |
Seattle Institute for Biomedical and Clinical Research Department of Defense |
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Information provided by: | Seattle Institute for Biomedical and Clinical Research |
ClinicalTrials.gov Identifier: | NCT00202449 |
The purposes of this study are:
Condition | Intervention |
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Stress Disorders, Post-Traumatic Sleep Disorders |
Drug: prazosin Drug: paroxetine Drug: Placebo |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study |
Official Title: | A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Related PTSD Nightmares and Sleep Disturbance |
Estimated Enrollment: | 210 |
Study Start Date: | July 2004 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Prazosin
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Drug: prazosin
taken by mouth, twice daily, titrated up to efficacy or a maximum of 5 mg at 10a and 25 mg at bedtime for duration of study
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2: Active Comparator
Paroxetine
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Drug: paroxetine
20 mg taken at 10a for duration of the study
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3: Placebo Comparator
Placebo
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Drug: Placebo
Placebo
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Trauma-related nightmares and sleep disruption that follow combat exposure are distressing and frequently treatment resistant symptoms that impair quality of life and overall function. These symptoms closely resemble core nighttime symptoms of posttraumatic stress disorder (PTSD), and are increasingly recognized in returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). Prazosin, a generically available brain active alpha-1 adrenergic receptor antagonist, markedly reduced or eliminated combat trauma-related nightmares and sleep disruption in 23 of 25 combat-exposed returnees from OIF at Madigan Army Medical Center (MAMC). The use of prazosin in OIF returnees was based on clinical efficacy of prazosin for trauma-related nightmares, sleep disturbance, and overall function in Vietnam combat veterans with chronic PTSD. The only drugs FDA approved for PTSD are the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine. However, SSRI effectiveness in combat trauma PTSD, especially for nighttime symptoms, remains questionable. This is a placebo-controlled clinical trial of prazosin vs. the SSRI paroxetine for combat trauma-related nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) clinical severity in OIF/OEF returnees. Both neurobiologic considerations and our preliminary clinical treatment data provide support for the proposed trial. Preclinical and clinical studies suggest a role for increased central nervous system (CNS) adrenergic outflow and/or responsiveness in PTSD pathophysiology. Possible mechanisms include alpha-1 adrenergic receptor-mediated effects on sleep physiology, corticotropin releasing hormone secretion, and disruption of cognitive processing.
Here we propose a double-blind, placebo-controlled parallel group 12 week clinical trial of prazosin vs. paroxetine to test the following hypotheses: Hypothesis 1. Prazosin will be more effective than paroxetine or placebo for reducing frequency and intensity of combat trauma-related nightmares (as measured by the "distressing dreams" item of the Clinician Administered PTSD Scale [CAPS]).
Hypothesis 2. Prazosin will be more effective than paroxetine or placebo for improving sleep quality (as measured by the Pittsburgh Sleep Quality Index [PSQI]). Hypothesis 3. Prazosin will be more effective than paroxetine or placebo for improving overall clinical status (as measured by the Clinical Global Impression of Change [CGIC]). Hypothesis 4. Prazosin will be better tolerated than paroxetine as measured by days retained in the study and frequency of adverse events.
Primary outcome measures will assess trauma-related nightmares, sleep disturbance and change in global clinical status: these will include the CAPS [59] Recurrent Distressing Dreams item, the PSQI (60) and the CGIC (58) score. Secondary outcome measures will include total CAPS score, the CAPS subscale scores (Reexperiencing/ Intrusions, Avoidance/Numbing, and Hyperarousal), the Nightmare Frequency Questionnaire (NFQ), Insomnia Severity Index, and measures of depressive signs and symptoms, quality of life, and number of study days completed.
Ages Eligible for Study: | 18 Years to 50 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Hollie A Holmes, BA | 206-277-6207 | hollie.holmes@va.gov |
Contact: Rebekah J Rein, JD | 206-768-5259 | rebekah.rein@va.gov |
United States, District of Columbia | |
Walter Reed Army Medical Center | Recruiting |
Washington, District of Columbia, United States, 20307 | |
Contact: Phoebe Kuesters 202-356-1012 ext 40315 Phoebe.Kuesters@NA.AMEDD.ARMY.MIL | |
Principal Investigator: Charles Engel, MD | |
United States, Washington | |
Madigan Army Medical Center | Recruiting |
Fort Lewis, Washington, United States, 98431 | |
Contact: Hollie A Holmes, BA 206-277-6207 hollie.holmes@va.gov | |
Contact: Rebekah J Rein, JD 206-768-5259 rebekah.rein@va.gov | |
Principal Investigator: Kris Peterson, MD |
Principal Investigator: | Murray Raskind, MD | Director, Mental Health Services and Director, Mental Illness Research, Education, and Clinical Center VA Puget Sound Health Care System |
Responsible Party: | VA Puget Sound Health Care System ( Murray Raskind, MD ) |
Study ID Numbers: | Raskind 0046, DoD #PR054292, UW HS #04-1469-V 02 |
Study First Received: | September 12, 2005 |
Last Updated: | March 3, 2009 |
ClinicalTrials.gov Identifier: | NCT00202449 History of Changes |
Health Authority: | United States: Institutional Review Board |
Prazosin Paroxetine Stress Disorders, Post-Traumatic Sleep Disorders |
Neurotransmitter Agents Adrenergic Agents Psychotropic Drugs Sleep Disorders Dyssomnias Stress Cardiovascular Agents Adrenergic alpha-Antagonists Antihypertensive Agents Serotonin Uptake Inhibitors Paroxetine |
Serotonin Stress Disorders, Traumatic Signs and Symptoms Anxiety Disorders Mental Disorders Prazosin Stress Disorders, Post-Traumatic Neurologic Manifestations Adrenergic Antagonists Antidepressive Agents, Second-Generation Antidepressive Agents |
Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Adrenergic Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Psychotropic Drugs Sleep Disorders Paroxetine Stress Disorders, Traumatic Signs and Symptoms Pathologic Processes Prazosin Mental Disorders Therapeutic Uses Stress Disorders, Post-Traumatic |
Antidepressive Agents, Second-Generation Antidepressive Agents Disease Nervous System Diseases Dyssomnias Stress Adrenergic alpha-Antagonists Cardiovascular Agents Antihypertensive Agents Serotonin Uptake Inhibitors Pharmacologic Actions Serotonin Agents Anxiety Disorders Neurologic Manifestations Adrenergic Antagonists |