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Prazosin vs Paroxetine in Combat Stress-Related Post-Traumatic Stress Disorder (PTSD) Nightmares & Sleep Disturbance

This study has been terminated.
(recruitment difficulties)
Sponsor:
Collaborators:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT00202449
First received: September 12, 2005
Last updated: June 11, 2012
Last verified: June 2012
  Purpose

The purposes of this study are:

  • to evaluate the efficacy and tolerability of the drug prazosin compared to placebo for combat stress-related nightmares, sleep disturbance and overall function in recently combat-exposed returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF).
  • to evaluate the effects of the selective serotonin reuptake inhibitor (SSRI) paroxetine on behavioral symptoms and overall function in this population.

Condition Intervention
Stress Disorders, Post-Traumatic
Sleep Disorders
Drug: prazosin
Drug: paroxetine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Related PTSD Nightmares and Sleep Disturbance

Resource links provided by NLM:


Further study details as provided by Seattle Institute for Biomedical and Clinical Research:

Primary Outcome Measures:
  • Change in Combat Trauma-related Nightmares Will be Assessed by the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams Item at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 12.

  • Change in Sleep Will be Assessed by the Pittsburgh Sleep Quality Index at Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 12.

  • Change in Global Trauma-related Symptom Severity and Functioning Will be Assessed by the Clinical Global Impression of Change at Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 measure evaluates change from baseline to Week 12.


Secondary Outcome Measures:
  • Additional Data on Change in Nightmares Will be Assessed by the PTSD Dream Rating Scale and Nightmare Frequency Questionnaire at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
  • Change in Depressive Symptoms Will be Assessed by the Hamilton Depression Rating Scale at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
  • Change in Quality of Life Will be Assessed by the Quality of Life Inventory at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
  • Study Days Completed as an Indicator of Medication Tolerability at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: July 2004
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Prazosin
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
Other Name: Minipress
Active Comparator: 2
Paroxetine
Drug: paroxetine
20 mg taken at 10a for duration of the study
Other Name: Paxil, Paxil CR
Placebo Comparator: 3
Placebo
Drug: Placebo
Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hazardous duty in Iraq or Afghanistan with the US Armed Forces during Operations Iraqi Freedom and Operation Enduring Freedom
  • Exposure to at least a moderate level of combat (>5 on Revised Combat Exposure Scale)
  • Good general medical health
  • Stable dose of non-excluded medications for at least 4 weeks prior to randomization
  • >5 on CAPS recurrent distressing dreams item
  • >5 on CAPS difficulty falling or staying asleep item

Exclusion Criteria:

  • Acute or significant chronic medical illness, preexisting hypotension or orthostatic hypotension, pancreatitis, gout, Ménière's disease, benign positional vertigo, narcolepsy, or any other unstable medical condition.
  • Women of childbearing potential with either positive pregnancy test or refusal to use effective birth control method will be excluded.
  • Lifetime schizophrenia, schizoaffective disorder, bipolar disorder, psychotic disorder or any Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) cognitive disorder, current delirium, substance dependence disorder within 3 months of the study, 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.
  • Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist or paroxetine or any other SSRI, no concurrent use of another alpha-1 antagonist agent, no concurrent use of an antidepressant (other than trazodone prescribed for sleep).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00202449

Locations
United States, District of Columbia
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307
United States, Washington
Madigan Army Medical Center
Fort Lewis, Washington, United States, 98431
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Principal Investigator: Murray Raskind, MD Director, Mental Health Services and Director, Mental Illness Research, Education, and Clinical Center VA Puget Sound Health Care System
  More Information

Publications:
Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT00202449     History of Changes
Other Study ID Numbers: Raskind 0046, DoD #PR054292, UW HS #04-1469-V 02
Study First Received: September 12, 2005
Results First Received: February 24, 2012
Last Updated: June 11, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
Prazosin
Paroxetine
Stress Disorders, Post-Traumatic
Sleep Disorders

Additional relevant MeSH terms:
Parasomnias
Sleep Disorders
Disease
Dyssomnias
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Paroxetine
Prazosin
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antihypertensive Agents
Cardiovascular Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on November 19, 2014