Targeting Stress-Induced Alcohol Relapse Risk With Doxazosin XL

Study Overview
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Brief Summary
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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.

Official Title
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Targeting Stress-Induced Alcohol Relapse Risk With Doxazosin XL

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Doxazosin XL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |