Neural and Hormonal Influences on Sex Differences in Risk for AUD

Alcohol Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04929288
• Other study ID #: 58758
• Secondary ID: R01AA028503
• Status: Recruiting
• Phase: N/A
• Start date: May 11, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: August 2023
• Source: Ohio State University
• Contact: Study Coordinator
• Phone: 8592575794
• Email: psychresearch[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 26 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

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.

Locations

Country	Name	City	State
United States	University Of Kentucky Psychology Research Lab	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Jessica Weafer	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

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