Alpha-1 Blockade for Alcohol Use Disorder (AUD)

Study Overview
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Brief Summary
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The goal of this research is to replicate findings previously conducted in a pilot trial and to understand, mechanistically, the role of stress in the development of AUD pharmacotherapies that target noradrenergic blockade.

Detailed Description
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16 week, between-subject, double-blind, randomized clinical trial (RCT) with doxazosin (16 mg, or maximum tolerated dose, MTD) compared to placebo in 184 treatment seeking individuals with AUD

Official Title
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A Focus on Alpha-1 Blockade as a Novel Pharmacological Treatment for AUD

Conditions
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Alcohol Use Disorder (AUD)

Intervention / Treatment
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* Drug: Doxazosin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age Meet the DSM-5 criteria for AUD Desire to reduce or quit alcohol drinking Breath alcohol (BrAC) = 0.00 at each visit In good health as confirmed by medical history, physical examination and lab tests Willing to adhere to the study procedures Understand informed consent and questionnaires in English at an 8th grade level Exclusion Criteria: Women who are breastfeeding or /positive urine test for pregnancy CrCl<60mL/min Suicide attempt in the last three months Current diagnosis of other substance disorder other than nicotine as assessed by self-report and urine toxicology screen at baseline Current use of medication that may interact with doxazosin and/or yohimbine History of allergy to any alpha receptor blockers Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score ≥ 8 Treatment with disulfiram, naltrexone, acamprosate, topiramate within 1 month prior to screening Treatment with any alpha-blocker Individuals with cardiac heat failure (CHF), as assessed by the medical history, the physical exam and the ECG. Baseline hypotension defined as BP reading lower than 90/60 mmHg Use of phosphodiesterase inhibitors (PDE5) erectile dysfunction medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: doxazosin<br>16 mg, or maximum tolerated dose (MTD) | Drug: Doxazosin<br>* 16 mg or maximum tolerated dose (MTD)<br>* Other names: Cardura;|
| Placebo Comparator: placebo<br>matching placebo | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol consumption | Number of drinks per week (DPW) in naturalistic condition as measured by the timeline follow-back (TLFB) | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol craving | We will measure alcohol craving using the Alcohol Craving Questionnaire (ACQ) after a cue-reactivity | one day | 
| Alcohol craving | Alcohol craving in naturalistic condition will be measured using craving the Obsessive Compulsive Drinking Scale (OCDS) | six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol use disorder, stress