Clinical Trial: Testing Doxazosin to Treat Stress Mechanisms in Alcoholism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized Controlled Trial Targeting Noradrenergic Stress Mechanisms in Alcoholism With Doxazosin

Brief Summary: Double-blind, placebo controlled, randomized controlled trial (RCT) for Alcohol Use Disorder examining the effects of doxazosin, a norepinephrine alpha1 receptor antagonist, on stress reactivity and clinical outcomes.

Detailed Summary:

OBJECTIVES:

1. To translate the preclinical evidence from animal models to stress-induced relapse in humans via direct pharmacological antagonism of the noradrenergic system in abstinent alcoholics with doxazosin, an alpha1 noradrenergic receptor blocker.
2. To screen the efficacy of doxazosin to target stress-related relapse mechanisms in abstinent alcoholics as a cost-effective first step to repurpose this alpha1 noradrenergic antagonist for relapse prevention in addiction.

PARTICIPANTS:

136 participants with an Alcohol Use Disorder in early abstinence.

STUDY OVERVIEW:

136 adults with an Alcohol Use Disorder in early abstinence (1-8 weeks abstinent) will participate in a randomized controlled trial (RCT) to examine the efficacy of 8 mg doxazosin (vs. placebo, between-subjects) on stress reactivity and clinical outcome measures (e.g., drinks/week, alcohol craving) during a 8 week treatment period. We assess doxazosin's impact on stress-related relapse mechanisms using a well-validated human model of stressor reactivity (No Shock, Predictable Shock, Unpredictable Shock [NPU] task) at baseline (pre-treatment) and after 4 weeks of treatment. The NPU task has strong translational ties to both methods (e.g., unpredictable vs. predictable electric shock) and measures (e.g., startle potentiation) from the preclinical literature in animals. This laboratory stress task serves as an attractive early surrogate endpoint post-treatment to assess treatment efficacy and examine stress mechanisms.

AIMS and HYPOTHESIS:

AIM 1:
Sponsor: University of Wisconsin, Madison

Current Primary Outcome:

• Startle potentiation during stress reactivity task [ Time Frame: 4 weeks ]
  Startle potentiation is measured in the NPU task
• No heavy drinking days [ Time Frame: 8 weeks ]
  Scored yes or no to indicate if participant reported any days of heavy drinking (> 4/3 standard drinks for men/women) during the 8 week assessment period
• Total number of alcoholic drinks [ Time Frame: 8 weeks ]
  Total number of alcoholic drinks consumed during the 8 week assessment period
• Total number of drinking days [ Time Frame: 8 weeks ]
  Total number of days that alcohol was consumed during the 8 week assessment period

Original Primary Outcome:

• Startle potentiation during stress reactivity task [ Time Frame: 4 weeks ]
  Startle potentiation is measured in the NPU task
• Continuous abstinence from alcohol Use [ Time Frame: 8 weeks ]
  Scored yes or no to indicate if completely abstinent from alcohol during the 8 week assessment period
• Total number of alcoholic drinks [ Time Frame: 8 weeks ]
  Total number of alcoholic drinks consumed during the 8 week assessment period
• Total number of drinking days [ Time Frame: 8 weeks ]
  Total number of days that alcohol was consumed during the 8 week assessment period

Current Secondary Outcome: Self-reported anxiety during stress reactivity task [ Time Frame: 4 weeks ]

Original Secondary Outcome: Same as current

Information By: University of Wisconsin, Madison

Dates:
Date Received: December 1, 2016
Date Started: April 12, 2017
Date Completion: December 2020
Last Updated: April 13, 2017
Last Verified: April 2017