Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees

This study has been completed.
Sponsor:
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00261729
First received: December 1, 2005
Last updated: December 2, 2009
Last verified: December 2009
  Purpose

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 OIF and OEF. To evaluate the effects of the SSRI paroxetine on behavioral symptoms and overall function in this population.


Condition Intervention
Sleep Disorders
Stress Disorders, Post-Traumatic
Drug: Paroxetine
Drug: Prazosin
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • CAPS recurrent distressing dreams item [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pittsburgh Sleep Quality Index [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]
  • Clinical Global Impression of Change [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]
  • Total CAPS [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]
  • Quality of Life Inventory [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]
  • Penn Alcohol Craving Scale [ Time Frame: baseline, 6 weeks, 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: July 2004
Study Completion Date: December 2009
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
paroxetine
Drug: Paroxetine
paroxetine 20 mg
Other Name: Paxil
Placebo Comparator: 2
placebo
Drug: placebo
placebo capsules
Experimental: 3
prazosin
Drug: Prazosin
Prazosin

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, M ni re'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 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 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: NCT00261729

Locations
United States, Washington
VA Puget Sound Health Care System, Seattle
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Investigators
Principal Investigator: Elaine Peskind, MD VA Puget Sound Health Care System, Seattle
  More Information

Publications:

Responsible Party: Peskind, Elaine - Principal Investigator, Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00261729     History of Changes
Obsolete Identifiers: NCT00240201
Other Study ID Numbers: MHBA-025-05S, 0026
Study First Received: December 1, 2005
Last Updated: December 2, 2009
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Paroxetine
Prazosin
Sleep Disorders
Stress Disorders, Post-Traumatic

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

ClinicalTrials.gov processed this record on July 22, 2014