Targeting Stress-Induced Alcohol Relapse Risk With Doxazosin XL

Participants (N=10/group) will consist of non-treatment seeking individuals with AUD.

Following informed consent and baseline screening, participants will partake in 3 stress induction sessions to assess their stress levels and cravings for alcohol. Participants will be randomized to receive either increasing doses of doxazosin XL (0, 4, and 8 mg) or placebo in a double-blind manner.

Study Overview

• Status: Withdrawn
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Doxazosin XL; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meet DSM-5 criteria for AUD;
• Report excessive alcohol use as defined by CDC guidelines in the past month (>7 drinks/week for woman, >14 drinks/week for men, >3 drinks/occasion for women>4 drinks/occasion for men)3.

Exclusion Criteria:

• Physical dependence on alcohol assessed using the SCID and Clinical Institute Withdrawal Assessment for Alcohol (CIWAA)41.
• Presenting an Alcohol Use Disorders Inventory (AUDIT) score indicative of severe alcohol dependence (≥13 for women, ≥15 for men);
• Meeting criteria for substance use disorder on drugs other than alcohol and nicotine;
• Currently taking a prescribed psychoactive medication (e.g., atomoxetine for ADHD). In addition, exclusion for those individuals taking CYP3A4 inhibitors. Most participants will not be taking any concomitant medications (including over-the-counter supplements). For those who are taking an allowed medication, the study physician will determine if the medications are CYP3A4 inhibitors.
• Medical conditions contraindicating doxazosin XL pharmacotherapy (e.g., postural hypotension);
• Taking contraindicated medications such as blood pressure medications;
• Be pregnant, nursing, or planning on becoming pregnant during the course of the study;
• Have any other illness, condition, or use of medications, which in the opinion of the PI and/or admitting physician would preclude safe and/or successful completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxazosin XL; Participants will receive increasing doses of doxazosin XL (0, 4, and 8 mg).	Drug: Doxazosin XL; Participants will be randomized to receive increasing doses of doxazosin XL (0, 4, and 8 mg).; Other Names: Cardura XL; Cardura
Placebo Comparator: Placebo; Participants will be randomized to receive a placebo for doxazosin XL.	Drug: Placebo; Participants will be randomized to receive a placebo for doxazosin XL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as study attendance	Attending sessions	Two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stress as assessed by salivary cortisol levels	Cortisol levels will be measured using the Cortisol ELISA Kit (Enzo Life Sciences).	baseline
Stress as assessed by salivary cortisol levels	Cortisol levels will be measured using the Cortisol ELISA Kit (Enzo Life Sciences).	Friday of week 1
Stress as assessed by salivary cortisol levels	Cortisol levels will be measured using the Cortisol ELISA Kit (Enzo Life Sciences).	Friday of week 2
Stress as assessed by self-report	Self-reported stress on a questionnaire	baseline
Stress as assessed by self-report	Self-reported stress on a questionnaire	Friday of week 1
Stress as assessed by self-report	Self-reported stress on a questionnaire	Friday of week 2
Stress as assessed by heart rate	Self-reported stress on a questionnaire	baseline
Stress as assessed by heart rate	Self-reported stress on a questionnaire	Friday of week 1
Stress as assessed by heart rate	Self-reported stress on a questionnaire	Friday of week 2
stress reactivity as assessed by increased blood pressure	Blood pressure	baseline
stress reactivity as assessed by increased blood pressure	Blood pressure	Friday of week 1
stress reactivity as assessed by increased blood pressure	Blood pressure	Friday of week 2
Alcohol craving as assessed by the Penn Alcohol Craving Scale (PACS)	The Penn Alcohol Craving Scale (PACS) is a 5 question self-report measure that assesses alcohol craving in the past week. Each question ranges from 0 (no craving) to 6 (highest craving). The total score on the scale ranges from 0 to 30, and higher scores indicate greater alcohol craving.	baseline
Alcohol craving as assessed by the Penn Alcohol Craving Scale (PACS)	The Penn Alcohol Craving Scale (PACS) is a 5 question self-report measure that assesses alcohol craving in the past week. Each question ranges from 0 (no craving) to 6 (highest craving). The total score on the scale ranges from 0 to 30, and higher scores indicate greater alcohol craving.	Friday of week 1
Alcohol craving as assessed by the Penn Alcohol Craving Scale (PACS)	The Penn Alcohol Craving Scale (PACS) is a 5 question self-report measure that assesses alcohol craving in the past week. Each question ranges from 0 (no craving) to 6 (highest craving). The total score on the scale ranges from 0 to 30, and higher scores indicate greater alcohol craving.	Friday of week 2
Alcohol Demand as assessed by the Brief Assessment of Alcohol Demand (BAAD) questionnaire	Alcohol demand will be assessed via the Brief Assessment of Alcohol Demand (BAAD), a 3-item questionnaire ("If drinks were free, how many would have?", "What is the maximum total amount you would spend on drinking?"; and "What is the maximum you would pay for a single drink?").	baseline
Alcohol Demand as assessed by the Brief Assessment of Alcohol Demand (BAAD) questionnaire	Alcohol demand will be assessed via the Brief Assessment of Alcohol Demand (BAAD), a 3-item questionnaire ("If drinks were free, how many would have?", "What is the maximum total amount you would spend on drinking?"; and "What is the maximum you would pay for a single drink?").	Friday of week 1
Alcohol Demand as assessed by the Brief Assessment of Alcohol Demand (BAAD) questionnaire	Alcohol demand will be assessed via the Brief Assessment of Alcohol Demand (BAAD), a 3-item questionnaire ("If drinks were free, how many would have?", "What is the maximum total amount you would spend on drinking?"; and "What is the maximum you would pay for a single drink?").	Friday of week 2
Delay discounting for alcohol as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000. In the case of alcohol discounting, the unit of alcohol (e.g., bottle, shot, glass, etc.) and cost of alcohol will be individually assessed in order to present choices that are monetarily equivalent to the money discounting task.	baseline
Delay discounting for alcohol as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000. In the case of alcohol discounting, the unit of alcohol (e.g., bottle, shot, glass, etc.) and cost of alcohol will be individually assessed in order to present choices that are monetarily equivalent to the money discounting task.	Friday of week 1
Delay discounting for alcohol as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000. In the case of alcohol delay discounting, the unit of alcohol (e.g., bottle, shot, glass, etc.) and cost of alcohol will be individually assessed in order to present choices that are monetarily equivalent to the money discounting task.	Friday of week 2
Delay Discounting for money as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000.	baseline
Delay Discounting for money as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000.	Friday of week 1
Delay Discounting for money as assessed by a computerized task	Delay discounting will be assessed for both money and alcohol using a computerized task at weekly clinic visits. Delays will range from 1 day to 25 years, and monetary values will range from $0 to $1,000.	Friday of week 2
Alcohol use as assessed by self-report	Self-reported drinks per day for the past week	baseline
Alcohol use as assessed by self-report	Self-reported drinks per day for the past week	Friday of week 1
Alcohol use as assessed by self-report	Self-reported drinks per day for the past week	Friday of week 2

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Jin Ho Yoon, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Anticipated): May 12, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: January 11, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Doxazosin
• Other Study ID Numbers: HSC-MS-17-0678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No