Prazosin for Treatment of Patients With Alcohol Dependence (AD) and Post Traumatic Stress Disorder (PTSD).

Phase 3

Completed

• Conditions: Alcohol Dependence; Stress Disorders, Post-Traumatic
• Interventions: Drug: Prazosin; Drug: Placebo

• Registration Number: NCT00744055
• Lead Sponsor: Yale University

Brief Summary

Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence.

The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD.

Detailed Description

Background:

There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with PTSD. Despite this, little is known about how to best treat individuals with comorbid AD and PTSD. The use of an alpha-1 adrenergic receptor antagonist represents a novel approach to treatment that may target symptoms of both AD and PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence.

Objective:

The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD. Methods: Thirty participants with a current diagnosis of AD and PTSD will be enrolled in a 13-week trial. They will be assigned, in a double-blind fashion, to either prazosin or placebo. Significance: This project will be the first to compare prazosin to placebo as effective treatments for reducing alcohol consumption and PTSD symptoms in patients with both AD and PTSD.

Study Timeline

• Study First Submitted: 2008-08-28
• Study First Submitted QC: 2008-08-28
• Study First Posted: 2008-08-29
• Study Start: 2009-01
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Results First Submitted: 2015-10-27
• Results First Submitted QC: 2015-12-11
• Results First Posted: 2016-01-18
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-17
• Last Update Posted: 2020-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

1. Males and females between the ages of 21-65 years old.
2. Current alcohol dependence, as determined by a structured clinical interview (Structured Clinical Interview for DSM-IV Axis I Disorders) (SCID) (First et al. 1996).
3. Current PTSD as determined by the Clinician Administered PTSD Scale for DSM-IV(CAPS) (Blake et al. 1995).
4. Patients with current alcohol dependence, with at least one recent episode of heavy drinking (defined as 5 or more drinks per drinking episode) over the past 14 days.
5. Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories (CBC w/ differential, TSH, Free-T4, ASAT, ALAT, GGT, BUN, creatinine, calcium, phosphorous, magnesium, total protein, albumin, electrolytes, VDRL, urinalysis, beta-HCG).
6. For women, negative pregnancy test and use of acceptable method of contraception.

Exclusion Criteria

1. Females who are pregnant or lactating.
2. Individuals with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT 5 times normal, abnormal BUN and creatinine, and unmanaged hypertension with BP more than 200/120) which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study.
3. Patients who meet current SCID criteria for the following major Axis I diagnoses (Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders).
4. History of substance dependence (other than alcohol, cocaine, tobacco or cannabis) by DSM-IV criteria in the last 30 days.
5. Individuals taking mood stabilizers and antipsychotic medications.
6. Individuals with a history of sensitivity to quinazolines or prazosin.
7. Individuals taking medications thought to influence alcohol consumption (naltrexone, disulfiram, acamprosate).
8. Individuals taking adrenergic medication (e.g. clonidine).
9. Agents that may interact with prazosin such as drugs with CNS depressant effects including tizanidine and xyrem.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prazosin	Prazosin	prazosin (16mg/day)
Placebo	Placebo	Placebo in identical looking capsule blister packs

Primary Outcome Measures

Name	Time	Method
Number of Drinking Days	12 weeks	Using the Timeline Follow Back method, a calendar method for assessing drug and alcohol use
Clinician-Administered PTSD Scale	12 weeks	Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD \>80=Extreme PTSD

Trial Locations

Locations (1)

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States