Effect of Allopregnanolone on Stress-induced Craving

Study Overview
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Brief Summary
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The goal of this study is to determine whether intravenous infusion of allopregnanolone (ALLO) attenuates stress-induced craving and stress-induced anxiety in a clinical laboratory setting. The secondary objective of this project is to characterize the behavioral effects of ALLO in heavy drinkers.

Detailed Description
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This is a double-blind, placebo-controlled study that will randomize 60 heavy at risk drinkers to 2 groups: targeted dose of targeted dose of 100 nM of ALLO (N=30) or placebo (N=30). Participants will receive a continuous infusion of ALLO (or placebo) for 175 min. Sixty min. after the start of the infusion, when ALLO levels are relatively stable, the stress induction paradigm will be introduced. Participants will be presented with a stress cue and a neutral cue in random order. Stress and neutral cues will consist of personalized 5 min. scripts created prior to testing. Measures of stress-induced craving and stress-induced anxiety will be presented before the cue (pre), immediately following the cue (post) and 10 min after (recovery).The study outcomes will include measures of stress-induced craving and stress-induced anxiety as well as measures of subjective mood effects, cognitive performance, and motor coordination.

Official Title
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Effect of Allopregnanolone on Stress-induced Craving

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Allopregnanolone
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-treatment seeking individuals with current DSM-5 AUD No current substance use disorder (except tobacco, alcohol, and marijuana) No current medical problems and normal ECG For women, not pregnant as determined by pregnancy screening, not breast feeding. Exclusion Criteria: Current major psychiatric illnesses including mood, psychotic, or anxiety disorders History of major medical illnesses; including liver diseases, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study Liver function tests (ALT or AST) greater than 3 times normal weight >120kg renal impairment patients on the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation (please note patients on psychotropic medications for current psychiatric conditions will also be excluded); and c) patients currently taking antibiotics or antifungals

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double blind, placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: allopregnanolone<br>allopregnanolone | Drug: Allopregnanolone<br>* neurosteroid<br>|
| Placebo Comparator: placebo<br>placebo | Drug: Placebos<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Urge Questionnaire (AUQ) | The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point Likert scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Scores range from 8-56 | 15 minutes | 
| The State-Trait Anxiety Inventory (STAI-6) | The State Trait Anxiety Inventory (STAI-6) is a psychological inventory based on a 4-point likert scale with 6 questions and is self-report. The STAI measures two types of anxiety - state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic. Higher scores are positively correlated with higher levels of anxiety. Scores range from 20-80. | 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biphasic Alcohol Effects scale (BAES) | The Biphasic Alcohol Effects Scale (BAES) is a 14-item self-report adjective rating scale that will be used to measure the stimulant and sedative effects of alcohol. Scores range from 0-140 | 30 minutes |