Effect of Allopregnanolone on Stress-induced Craving

Yale University

Status and phase: Completed; Phase 1

Conditions: Alcohol Use Disorder

Treatments: Drug: Placebos; Drug: Allopregnanolone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04015869

1R21AA024917-01A1 (U.S. NIH Grant/Contract)

2000021601

Details and patient eligibility

About

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.

Full description

This is a double-blind, placebo-controlled study that will randomize heavy "at risk" drinkers to 2 groups: targeted dose of 100 nM of ALLO or placebo. Participants will receive a continuous infusion of ALLO (or placebo) for approximately 175 min. Sixty minutes 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-minute 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 minutes after (recovery). An alcohol infusion (40mg%) begins at approximately 120 minutes into ALLO Infusion. Once the alcohol infusion has reached the targeted dose of 40mg% the infusion is clamped for approximately 20 minutes. 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.

Enrollment: 10 patients

Sex: All

Ages: 21 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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10 participants in 2 patient groups, including a placebo group

allopregnanolone

Active Comparator group

Description:

Allopregnanolone infusion dose of 100nM over 175 min

Treatment:

Drug: Allopregnanolone

placebo

Placebo Comparator group

Description:

Placebo infusion

Treatment:

Drug: Placebos