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CSP #563 - Prazosin and Combat Trauma PTSD (PACT)

Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: PTSD; Sleep Disorders

Intervention: prazosin (Drug); placebo (Other)

Phase: Phase 3

Status: Completed

Sponsored by: Department of Veterans Affairs

Official(s) and/or principal investigator(s):
Murray Raskind, MD, Study Chair, Affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA

Summary

Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in veterans. Increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of overall PTSD and treatment-resistant nighttime symptoms. Placebo-controlled pilot studies demonstrate that the generically available CNS-active alpha-1 adrenoreceptor antagonist prazosin substantially reduces PTSD trauma nightmares and sleep disturbance and improves global clinical status (sense of well being and ability to function) in veterans. Objective: The primary objective is to demonstrate in a large multi-site placebo-controlled trial in veterans with war zone trauma-induced PTSD that prazosin is efficacious for PTSD trauma nightmares, sleep disturbance, and global clinical status. A secondary objective is to demonstrate prazosin effectiveness for these outcome measures during clinically meaningful long-term (26 week) maintenance treatment of PTSD. We will also address prazosin efficacy and long-term effectiveness for improving total PTSD symptoms, comorbid depression, quality of life, and physical functioning. Methods: This 26 week randomized double-blind placebo-controlled study is designed to demonstrate both short term efficacy and long term effectiveness of prazosin for PTSD. The research design encompasses a shorter-term, more tightly controlled efficacy component and a longer-term, more .real world. effectiveness component. Three hundred twenty-six veterans

with war zone - related PTSD and persistent trauma nightmares will be randomized 1: 1 to

prazosin or placebo. Study drug will be increased using a flexible dose titration schedule based on clinical response and adverse effects to an optimum maintenance dose (1-20 mg/day). During the first 10 weeks of the study, participants will be randomized to prazosin or placebo. Previous psychotropic medications and/or psychotherapy will be maintained constant. Short term efficacy will be determined during the first 10 weeks. During the remaining 16 weeks of the 26 week trial, subjects will continue to receive stable-dose double-blind prazosin or placebo, but will have the option to receive additional psychotropic medications and/or psychotherapeutic interventions, as needed, per the judgment of the study Clinician Prescriber. It is hypothesized that prazosin will remain more clinically effective than placebo at the end of the 26-week trial, demonstrating that prazosin adds benefit over-and-above other treatments that are naturalistically administered by providers in a .real world. clinical setting. Prazosin will be judged efficacious at 10 weeks if superior to placebo on all three primary outcome measures assessing trauma nightmares, sleep disturbance, and global clinical status: the Recurrent Distressing Dreams item of the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression of Change (CGIC). Secondary outcome measures will assess prazosin effects on total PTSD symptoms, depression, physical functioning, and quality of life. Adverse effects and cardiovascular measures, including supine and standing blood pressure (BP) and heart rate (HR) will be assessed.

Clinical Details

Official title: CSP #563 - Prazosin and Combat Trauma PTSD (PACT)

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Clinical Global Impression of Change

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age >18 years.

- Exposure to one or more life-threatening war zone trauma events per the Combat

- Exposure Scale [78] and documented by DD-214, Combat Action Ribbon (Marines), Combat

Infantry Badge (Army), or other clear evidence of war zone trauma exposure.

- Eligible for VA health care.

- 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).

- Capable of giving informed consent.

- Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to

randomization.

- Psychotherapeutic treatment stable for at least 4 weeks prior to randomization.

- Good general medical health (see Medical Exclusion Criteria below).

- Female participants must agree to use a reliable form of birth control during the

study. Exclusion Criteria: Medical:

- Acute or unstable chronic medical illness, including unstable angina, recent

myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic <110) or orthostatic hypotension (systolic drop > 20mmHg after two minutes standing or any drop accompanied by dizziness); chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy.

- Untreated sleep apnea, diagnosed by a sleep study, is exclusionary. Treated sleep

apnea (e. g., CPAP, surgery) will not be exclusionary.

- Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.

- Wounds requiring surgery, embedded shrapnel, and recent surgical amputation do not

comprise an exclusion if the individual is otherwise medically eligible.

- Women of childbearing potential with positive pregnancy test or refusal to use

effective birth control method, or who are breastfeeding will be excluded. Psychiatric/Behavioral:

- Meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic

disorder NOS, delirium, or any DSM-IV cognitive disorder.

- Exclusion for psychotic disorder is not to be confused with combat trauma-induced

reexperiencing symptoms (transient dissociative states or flashbacks), which will not be exclusionary.

- Substance dependence disorder within 3 months or any current substance dependence

(stable methadone maintenance will not be exclusionary).

- 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.

- Nonsuicidal depression comorbid with PTSD will not be exclusionary (see below).

Medications/Therapies:

- Current use of prazosin or other alpha-1 antagonist.

- Previous adequate trial of prazosin for PTSD.

- Subjects on trazodone will undergo a 2-week washout period before baseline

assessment. (Combining prazosin and trazodone may increase risk of priapism).

- Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be

permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers. Following achieving stable dose of study drug, sildenafil, tadalafil, and vardenafil will be permitted at 1/2 the usual starting dose.

- Stimulants or alternative medications with stimulant properties (e. g., ephedra).

- Recent exposure therapy and/or Eye Movement Desensitization and Reprogramming (EMDR).

These therapies must have been completed > 4 weeks before randomization.

- Other psychotropic medications and/or maintenance psychotherapy at a stable dose for

at least 4 weeks will not be exclusionary.

Locations and Contacts

VA Medical Center, Loma Linda, Loma Linda, California 92357, United States

VA Medical Center, Long Beach, Long Beach, California 90822, United States

VA Palo Alto Health Care System, Palo Alto, California 94304-1290, United States

VA Medical Center, Miami, Miami, Florida 33125, United States

Atlanta VA Medical and Rehab Center, Decatur, Decatur, Georgia 30033, United States

VA Medical Center, Kansas City MO, Kansas City, Missouri 64128, United States

New Mexico VA Health Care System, Albuquerque, Albuquerque, New Mexico 87108-5153, United States

New York Harbor HCS, New York, New York 10010, United States

VA Medical Center, Durham, Durham, North Carolina 27705, United States

Salisbury VAMC, Salisbury, North Carolina 28144, United States

VA Medical Center, Providence, Providence, Rhode Island 02908, United States

WJB Dorn Veterans Hospital, Columbia, Columbia, South Carolina 29209, United States

VA Salt Lake City Health Care System, Salt Lake City, Salt Lake City, Utah 84148, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA, Seattle, Washington 98108, United States

Wlliam S. Middleton Memorial Veterans Hospital, Madison, Madison, Wisconsin 53705, United States

Additional Information

Starting date: January 2010
Last updated: July 28, 2014

Page last updated: August 23, 2015

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