Effect of Allopregnanolone on Stress-induced Craving

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebos; Drug: Allopregnanolone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healtcase System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebos; placebo
Active Comparator: allopregnanolone	Drug: Allopregnanolone; neurosteroid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Elizabeth Ralevski, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

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; Central Nervous System Depressants; Anesthetics; Pregnanolone
• Other Study ID Numbers: 2000021601; 1R21AA024917-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No