Neural and Hormonal Influences on Sex Differences in Risk for AUD

Sponsor

Jessica Weafer (Other)

Overall Status

Recruiting

CT.gov ID

NCT04929288

Collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)

100

Enrollment

Location

Arms

49.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The sex gap in alcohol consumption is closing rapidly, due to alarming increases among women. From 2002-2013, Alcohol Use Disorder (AUD) increased 84% for women, compared to 35% for men. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD. Current addiction models propose three domains that drive problematic alcohol use and serve as candidate sex-specific risk factors: executive function, negative emotionality, and incentive salience. Data suggest that poor inhibitory control, a key component of executive function, is a stronger risk factor for women than for men. Moreover, there is have preliminary evidence that female drinkers show less engagement of neural inhibitory circuitry, and that this sex difference is influenced by estradiol. However, the degree to which hormonally-moderated sex differences in executive function extend to the negative emotionality and incentive salience domains, and how these sex differences influence current and future drinking is unknown.

The goal of this study is to identify the mechanisms underlying sex-specific risk for AUD, and ultimately to help develop sex-specific prevention and treatment efforts. The overall objective of this trial is to determine the neural and hormonal factors contributing to sex-specific risk for AUD in three addiction domains: inhibitory control (executive function), negative emotionality, and alcohol cue reactivity (incentive salience).

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Alcohol	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Sex Differences in Risk for Alcohol Use Disorder: Neural and Hormonal Influences

Actual Study Start Date :

May 11, 2021

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Males Participants in this group will be adult male drinkers.	Drug: Alcohol Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.
Experimental: Females Participants in this group will be adult female drinkers. Data will be segregated by menstrual cycle phase.	Drug: Alcohol Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.

Arm

Intervention/Treatment

Experimental: Males

Participants in this group will be adult male drinkers.

Drug: Alcohol

Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.

Experimental: Females

Participants in this group will be adult female drinkers. Data will be segregated by menstrual cycle phase.

Drug: Alcohol

Outcome Measures

Primary Outcome Measures

Neural inhibitory function [13 minutes]
One measure of neural inhibitory function during performance of the stop signal task will be activity (as measured by BOLD % signal change)
Neural inhibitory function [13 minutes]
The other measure of neural inhibitory function during performance of the stop signal task will be functional connectivity for the StopInh>Go contrast.
Neural negative emotionality [14 minutes]
One measure of neural negative emotionality during performance of the Emotional Pictures Task will be activity (as measured by BOLD % signal change)
Neural negative emotionality [14 minutes]
The other measure of neural negative emotionality during performance of the Emotional Pictures Task will be functional connectivity for the Negative>Neutral contrast.
Neural alcohol cue reactivity [12 minutes]
One measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be activity (as measured by BOLD % signal change)
Neural alcohol cue reactivity [12 minutes]
The other measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be functional connectivity for the Alcohol>Neutral contrast.
Intravenous alcohol self-administration (IV-ASA) [60 minutes]
One measure of IV-ASA will be peak BrAC (mg%; highest BrAC obtained during the IV-ASA period)
Intravenous alcohol self-administration (IV-ASA) [60 minutes]
Another measure of IV-ASA will be whether or not a participant reached binge level of alcohol exposure (80mg%)
Intravenous alcohol self-administration (IV-ASA) [60 minutes]
The final measure of IV-ASA will be time to reach binge level of alcohol exposure (80mg%)
Self-reported current alcohol consumption [20 minutes]
One measure of current alcohol consumption will be number of binge days (4/5 or more drinks in a sitting for women/men) as determined by responses on the Timeline Followback.
Self-reported current alcohol consumption [20 minutes]
The other measure of current alcohol consumption will be average peak BrAC obtained on drinking days over the past 5 days, as determined by responses on the Timeline Followback.
Prospective alcohol consumption [18 months]
One measure of prospective alcohol consumption will be number of binge episodes as determined by responses on the 90-day Timeline Followback.
Prospective alcohol consumption [18 months]
The other measure of prospective alcohol consumption will be drinking days per month, as determined by responses on the 90-day Timeline Followback.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 26 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

consume 4/5 drinks per week
fluent in English
high school education
right-handed
regular menstrual cycles (women)

Exclusion Criteria:

serious medical problems
body weight <110 or >210 lbs
current medical or psychiatric conditions requiring medication for which alcohol is contraindicated
substance use disorder other than alcohol
current or recent history of inpatient/intensive treatment for addictive behaviors
pregnant, nursing, on hormonal contraception
contraindications for fMRI
smoking > 5 cigarettes per day