NCT04015869

Effect of Allopregnanolone on Stress-induced Craving

Completed Phase 1 Results posted Last updated 22 August 2025

What this trial tests

Phase 1 trial testing Allopregnanolone in Alcohol Use Disorder in 10 participants. Completed in 1 September 2023.

Timeline

1 July 2019

Primary endpoint
1 September 2023

1 September 2023

Quick facts

Lead sponsor	Yale University
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	health services research
Enrollment	10
Start date	1 July 2019
Primary completion	1 September 2023
Estimated completion	1 September 2023
Sites	1 location across United States

Drugs / interventions tested

• Allopregnanolone — full drug profile →
• Placebos — full drug profile →

Conditions studied

• Alcohol Use Disorder — all drugs for Alcohol Use Disorder →

Sponsor

Yale University

Who can join

Adults 21 to 50, any sex, with Alcohol Use Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Alcohol Urge Questionnaire (AUQ) Pre-script Primary · Pre-Script 40 minutes before trauma/neutral script is presented

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).

Group	Value	95% CI
Allopregnanolone Trauma Script	24.45	± 6.18
Allopregnanolone Neutral Script	21.51	± 5.05
Placebo Trauma Script	19.15	± 6.18
Placebo Neutral Script	26.29	± 5.05

The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Pre-Script Primary · Pre-Script 40 minutes before trauma/neutral script is presented

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:

Group	Value	95% CI
Allopregnanolone Trauma Script	1.4	± 0.26
Allopregnanolone Neutral Script	1.0	± 0.26
Placebo Trauma Script	1.0	± 0.26
Placebo Neutral Script	1.4	± 0.26

Alcohol Urge Questionnaire (AUQ) Post-Script Primary · Post-Script 5 minutes after trauma/neutral script is presented

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).

Group	Value	95% CI
Allopregnanolone Trauma Script	27.09	± 6.10
Allopregnanolone Neutral Script	21.50	± 7.61
Placebo Trauma Script	14.12	± 6.63
Placebo Neutral Script	24.70	± 7.61

Alcohol Urge Questionnaire (AUQ) Recovery Primary · Recovery 10 minutes after trauma/neutral script is presented

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).

Group	Value	95% CI
Allopregnanolone Trauma Script	25.65	± 6.56
Allopregnanolone Neutral Script	25.76	± 6.90
Placebo Trauma Script	17.03	± 7.14
Placebo Neutral Script	24.70	± 7.61

Biphasic Alcohol Effects Scale (BAES) Sedation Items - Pre-Script Secondary · Pre-Script 40 minutes before trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.

Group	Value	95% CI
Allopregnanolone	6.4	± 2.71
Placebo	6.2	± 2.71

Biphasic Alcohol Effects Scale (BAES) Sedation Items Secondary · Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)

Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol. Data presented here is mean at 90 minutes.

Group	Value	95% CI
Allopregnanolone	10.6	± 3.38
Placebo	5.2	± 3.38

Biphasic Alcohol Effects Scale (BAES) Sedation Items - Target Alcohol Dose (40mg%) Secondary · Target Alcohol dose (40mg%) 90 minutes after trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.

Group	Value	95% CI
Allopregnanolone	5.8	± 3.72
Placebo	4.2	± 3.72

Biphasic Alcohol Effects Scale (BAES) Sedation Items - End of Test Day Secondary · End of test day 150 minutes after trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.

Group	Value	95% CI
Allopregnanolone	2.8	± 2.54
Placebo	6.4	± 2.54

Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Pre-Script Secondary · Pre-Script 40 minutes before trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.

Group	Value	95% CI
Allopregnanolone	25.8	± 6.8
Placebo	14.2	± 6.8

Biphasic Alcohol Effects Scale (BAES) Stimulation Items Secondary · Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)

Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol. Data presented here is mean at 90 minutes.

Group	Value	95% CI
Allopregnanolone	17.4	± 8.18
Placebo	15.6	± 8.18

Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Target Alcohol Dose (40mg%) Secondary · Target Alcohol Dose (40mg%) 90 minutes after trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.

Group	Value	95% CI
Allopregnanolone	26.2	± 5.36
Placebo	31.4	± 5.36

Biphasic Alcohol Effects Scale (BAES) Stimulation Items - End of Test Day Secondary · End of Test Day 150 minutes after trauma/neutral script is presented

Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.

Group	Value	95% CI
Allopregnanolone	17.6	± 4.18
Placebo	17.4	± 4.18

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune treatments for alcohol use disorder: A translational framework.
   Meredith LR, Burnette EM, Grodin EN, Irwin MR, et al · · 2021 · cited 50× · PMID 34343618 · DOI 10.1016/j.bbi.2021.07.023
2. Pharmacological interventions for alcohol use disorder: novel insights from recent clinical trials.
   McManus KR, Ray LA. · · 2026 · PMID 41611606 · DOI 10.1080/17512433.2026.2625341