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

Sponsor

US Department of Veterans Affairs (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT00261729

Collaborator

(none)

210

Enrollment

Location

Arms

Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Sleep Disorders Stress Disorders, Post-Traumatic	Drug: Paroxetine Drug: Prazosin Drug: placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2004

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 paroxetine	Drug: Paroxetine paroxetine 20 mg Other Names: Paxil
Placebo Comparator: 2 placebo	Drug: placebo placebo capsules
Experimental: 3 prazosin	Drug: Prazosin Prazosin

Arm

Intervention/Treatment

Experimental: 1

paroxetine

Drug: Paroxetine

paroxetine 20 mg

Other Names:

Paxil

Placebo Comparator: 2

placebo

Drug: placebo

placebo capsules

Experimental: 3

prazosin

Drug: Prazosin

Prazosin

Outcome Measures

Primary Outcome Measures

CAPS recurrent distressing dreams item [baseline, 6 weeks, 12 weeks]

Secondary Outcome Measures

Pittsburgh Sleep Quality Index [baseline, 6 weeks, 12 weeks]
Clinical Global Impression of Change [baseline, 6 weeks, 12 weeks]
Total CAPS [baseline, 6 weeks, 12 weeks]
Quality of Life Inventory [baseline, 6 weeks, 12 weeks]
Penn Alcohol Craving Scale [baseline, 6 weeks, 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).