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

• ClinicalTrials.gov Identifier: NCT00990106
• Recruitment Status: Completed
• First Posted: October 6, 2009
• Results First Posted: September 1, 2014
• Last Update Posted: May 23, 2018
• Sponsor: Seattle Institute for Biomedical and Clinical Research
• Collaborators: United States Department of Defense; VA Puget Sound Health Care System; National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Seattle Institute for Biomedical and Clinical Research

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Stress Disorders, Post-Traumatic; Combat Disorders; Sleep Disorders	Drug: prazosin hydrochloride; Drug: placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled Augmentation Trial of Prazosin for PTSD
• Study Start Date: September 2009
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item [ Time Frame: Baseline to Week 15 ]
   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.
2. Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline to Week 15 ]
   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.
3. Clinical Global Impression of Change (CGIC) [ Time Frame: Change from Baseline to Week 15 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

United States Department of Defense

VA Puget Sound Health Care System

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Study Chair: Murray Raskind, MD; Department of Veterans Affairs Puget Sound Health Care System

More Information

Publications of Results:

Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O'Connell J, Pritzl D, Feiszli K, Petrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013 Sep;170(9):1003-10. doi: 10.1176/appi.ajp.2013.12081133.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raskind MA, Millard SP, Petrie EC, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Hill J, Daniels C, Hendrickson R, Peskind ER. Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin. Biol Psychiatry. 2016 Nov 15;80(10):736-742. doi: 10.1016/j.biopsych.2016.03.2108. Epub 2016 Apr 11.

• Responsible Party: Seattle Institute for Biomedical and Clinical Research
• ClinicalTrials.gov Identifier: NCT00990106
• Other Study ID Numbers: PT074250; 1P20AA017839-01 ( U.S. NIH Grant/Contract )
• First Posted: October 6, 2009
• Results First Posted: September 1, 2014
• Last Update Posted: May 23, 2018
• Last Verified: April 2018

Keywords provided by Seattle Institute for Biomedical and Clinical Research:

posttraumatic stress disorder; PTSD; nightmares; prazosin; sleep disturbance; combat trauma

Additional relevant MeSH terms:

Sleep Wake Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Combat Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Prazosin; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs