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

This study has been completed.
Sponsor:
Collaborators:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT00990106
First received: October 2, 2009
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.

Condition Intervention
Stress Disorders, Post-Traumatic
Combat Disorders
Sleep Disorders
Drug: prazosin hydrochloride
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 Augmentation Trial of Prazosin for PTSD

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item [ Time Frame: Baseline to Week 15 ] [ 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 15.

  • Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline to Week 15 ] [ 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 15.

  • Clinical Global Impression of Change (CGIC) [ Time Frame: Change from Baseline to Week 15 ] [ 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 measures the proportion of responders who were rated markedly or moderately improved at Week 15 compared to Baseline.


Secondary Outcome Measures:
  • Clinician-Administered PTSD Scale (CAPS) Total Score [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • CAPS Symptom Clusters (Reexperiencing/Intrusions, Numbing/Avoidance, and Hyperarousal) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • Hamilton Depression Scale (HAM-D) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • Quality Of Life Inventory (QOLI) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • SF-12V [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • Penn Alcohol Craving Scale (PACS) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]
  • Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) [ Time Frame: Baseline, Weeks 7, 11 and 15 ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: September 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: prazosin hydrochloride

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
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.
Other Names:
  • prazosin
  • Pfizer Minipress
Placebo Comparator: placebo

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
placebo
Other Name: sugar pill

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00990106

Locations
United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98108
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Study Chair: Murray Raskind, MD Department of Veterans Affairs Puget Sound Health Care System
  More Information

Publications:
Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT00990106     History of Changes
Other Study ID Numbers: PT074250, 1P20AA017839-01
Study First Received: October 2, 2009
Results First Received: April 16, 2014
Last Updated: August 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
posttraumatic stress disorder
PTSD
nightmares
prazosin
sleep disturbance
combat trauma

Additional relevant MeSH terms:
Combat Disorders
Disease
Parasomnias
Sleep Disorders
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Prazosin
Adrenergic Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014