Prazosin Treatment for Combat Trauma PTSD (Post-Traumatic Stress Disorder) Nightmares and Sleep Disturbance

• ClinicalTrials.gov Identifier: NCT00108420
• Recruitment Status: Completed
• First Posted: April 15, 2005
• Last Update Posted: January 21, 2009
• Sponsor: US Department of Veterans Affairs
• Information provided by: VA Office of Research and Development

Study Description

Brief Summary:

The purpose of this study is to determine whether prazosin will reduce the incidence of nightmares, sleep disturbance, and overall symptoms in combat trauma-exposed individuals with PTSD.

Condition or disease	Intervention/treatment	Phase
Stress Disorder, Post-Traumatic	Drug: Prazosin	Phase 4

Detailed Description:

The combat stress-related nightmares and sleep disturbance that often follow exposure to military combat are distressing and frequently persistent symptoms that impair quality of life and both occupational and social (e.g., family) function. One of the most frequently reported and most troubling symptoms of PTSD is trauma-content nightmares. These nighttime symptoms have been notoriously resistant to treatment with psychotropic medications such as anxiolytics, the SSRIs, and sedating antihistamines such as cyproheptadine. The SSRIs sertraline (Zoloft®) and paroxetine (Paxil®) are the only drugs FDA approved for PTSD. This approval was based on modest overall PTSD improvement compared to placebo in large multicenter trials that enrolled almost exclusively noncombat trauma subjects. Placebo-controlled SSRI trials for PTSD in combat veterans have been negative or equivocal.

Neurobiologic data suggest that combat stress-related nightmares and sleep disturbance in PTSD are related to enhanced central nervous system (CNS) adrenergic activity, particularly at night. Prazosin is a CNS-active, non-sedating alpha-1 antagonist that has long been generically available for the treatment of hypertension and benign prostatic hypertrophy. We recently demonstrated in Vietnam combat veterans with chronic PTSD that prazosin is robustly effective for previously treatment refractory combat trauma related nightmares, sleep disturbance and overall PTSD severity and functional impairment.

The goal of this study is to evaluate the efficacy and tolerability of prazosin compared to placebo for combat stress-related nightmares, sleep disturbance and overall function in combat-trauma exposed persons with PTSD.

Primary outcome measures will be Clinical Global Impression of Change, Recurrent Distressing Dreams and Difficulty Falling and Staying Asleep items of the CAPS, total CAPS (exclusive of the dreams and sleep items), and the Pittsburgh Sleep Quality Index. Depression and quality of life also will be assessed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Prazosin Treatment for Combat Trauma PTSD Nightmares and Sleep Disturbance
• Study Start Date: October 2003
• Study Completion Date: March 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Clinical Global Impression of Change
2. Recurrent Distressing Dreams and Difficulty Falling and Staying Asleep items of the CAPS
3. Total CAPS (exclusive of the dreams and sleep items)
4. The Pittsburgh Sleep Quality Index
5. Depression
6. Quality of life

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:

• Combat-trauma exposed persons with a diagnosis of PTSD
• No diagnosis of lifetime schizophrenia, schizoaffective disorder, bipolar disorder, psychotic disorder, or any DSM-IV cognitive disorder; current delirium, or substance dependence disorder within 3 months of the study or current substance use other than alcohol (no more than 2 drinks/day); severe psychiatric instability or situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others
• In good general medical health (no acute or significant chronic medical illness, including unstable angina, recent myocardial infarction, history of congestive heart failure, preexisting hypotension [systolic <110] or orthostatic hypotension [systolic drop > 20 mmHg after two minutes standing or any drop with dizziness]; insulin-dependent diabetes mellitus; chronic renal or hepatic failure, pancreatitis, gout, Meniere's disease, benign positional vertigo, narcolepsy, allergy or previous adverse reaction to prazosin or other alpha-1 antagonist, or any unstable medical condition).
• Stable dose of nonexcluded medications for concurrent stable medical conditions for at least 4 weeks prior to randomization.
• Specific criteria used to validate presence of combat stress-related nightmares and sleep disturbance will include: score > 5 (of a maximum score of 8) on the CAPS Recurrent Distressing Dreams item. (CAPS score >5 places subjects in the upper third of nightmare severity) or score > 5 (of a maximum score of 8) on the CAPS Difficulty Falling or Staying Asleep item.

Contacts and Locations

Locations

United States, Washington

VA Puget Sound Health Care System

Seattle, Washington, United States, 98108

Sponsors and Collaborators

US Department of Veterans Affairs

More Information

• ClinicalTrials.gov Identifier: NCT00108420
• Other Study ID Numbers: CLIN-018-02F
• First Posted: April 15, 2005
• Last Update Posted: January 21, 2009
• Last Verified: May 2007

Keywords provided by VA Office of Research and Development:

Prazosin; Stress Disorders, Post-traumatic

Additional relevant MeSH terms:

Dyssomnias; Parasomnias; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases; 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