Effect of Allopregnanolone on Stress-induced Craving

NCT04015869 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20000216011R21AA024917-01A1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (12)

• Alcohol Urge Questionnaire (AUQ) Pre-script

  The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point 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). Total scores range from 8 (strongly disagree) to 56 (strongly agree).

  Pre-Script 40 minutes before trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Pre-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)

  Pre-Script 40 minutes before trauma/neutral script is presented

• Alcohol Urge Questionnaire (AUQ) Post-Script

  The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point 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). Total scores range from 8 (strongly disagree) to 56 (strongly agree).

  Post-Script 5 minutes after trauma/neutral script is presented

• Alcohol Urge Questionnaire (AUQ) Recovery

  The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point 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). Total scores range from 8 (strongly disagree) to 56 (strongly agree).

  Recovery 10 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Post-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)

  Post-Script 5 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Recovery

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)

  Recovery 10 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Pre-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)

  Pre-Script 40 minutes before trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Post-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)

  Post-Script 5 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Recovery

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)

  Recovery10 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I am Worried - Pre-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)

  Pre-Script 40 minutes before trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I am Worried - Post-Script

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)

  Post-Script 5 minutes after trauma/neutral script is presented

• The State-Trait Anxiety Inventory (STAI-6) I am Worried - Recovery

  The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)

  Recovery 10 minutes after trauma/neutral script is presented

Secondary Outcomes (8)

• Biphasic Alcohol Effects Scale (BAES) Sedation Items - Pre-Script

  Pre-Script 40 minutes before trauma/neutral script is presented

• Biphasic Alcohol Effects Scale (BAES) Sedation Items

  Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)

• Biphasic Alcohol Effects Scale (BAES) Sedation Items - Target Alcohol Dose (40mg%)

  Target Alcohol dose (40mg%) 90 minutes after trauma/neutral script is presented

• Biphasic Alcohol Effects Scale (BAES) Sedation Items - End of Test Day

  End of test day 150 minutes after trauma/neutral script is presented

• Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Pre-Script

  Pre-Script 40 minutes before trauma/neutral script is presented

Study Arms (2)

allopregnanolone

ACTIVE COMPARATOR

Allopregnanolone infusion dose of 100nM over 175 min

Drug: Allopregnanolone

placebo

PLACEBO COMPARATOR

Placebo infusion

Drug: Placebos

Interventions

Allopregnanolone DRUG

neurosteroid

allopregnanolone

Placebos DRUG

placebo

placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Non-treatment seeking individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD)
• No current substance use disorder (except tobacco, alcohol, and marijuana)
• No current medical problems and normal electrocardiogram (ECG)
• For women, not pregnant as determined by pregnancy screening, not breast feeding.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

VA Connecticut Healtcase System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Pregnanolone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Elizabeth Ralevski
• Organization: Yale University School of Medicine, Department of Psychiatry

Elizabeth.Ralevski@yale.edu

203-932-5711

Study Officials

• Elizabeth Ralevski, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Model Details: Randomized, double blind, placebo controlled

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: July 11, 2019
• Study Start: July 1, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)