Clinical trial NCT04543942: Sex Differences in Risk for Alcohol Abuse
Official title: Neurobiological Factors Underlying Sex Differences in Risk for Alcohol Abuse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Abuse
Keywords: brain activation during response inhibition
BARI
fMRI
stop signal task
sex difference
menstrual
inhibitory control
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2020-09-10
Enrollment: 28
Sex: ALL
Minimum age (years): 21
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study will determine the neural and hormonal mechanisms underlying sex differences in sensitivity to the disinhibiting effects of alcohol in heavy drinkers.

Detailed description: Alcohol abuse inflicts enormous physical, emotional, and financial burdens on the individual and society at large. Knowing who is at risk for alcohol abuse, and why, is crucial for the development of effective prevention and treatment strategies. Alcohol abuse has been traditionally considered a male-oriented problem and as a consequence research on risk factors specific to women has been minimal. However, the sex gap in substance abuse is closing rapidly, and findings from both animal and human studies suggest that females are actually more vulnerable to drug use than males. As such, there is an urgent need to identify sex differences in risk factors for alcohol abuse in order to develop sex-specific prevention and treatment efforts. One clear candidate risk factor is poor inhibitory control, both in terms of baseline levels of inhibition and sensitivity to the disinhibiting effects of alcohol. Recent studies suggest that sex hormones affect inhibitory control in drug-free individuals, potentially contributing to sex differences in baseline levels of inhibition. However, the degree to which fluctuations in sex hormones influence sex differences in inhibition-related brain function in sober and intoxicated individuals is not known. The proposed project will determine the neural and hormonal mechanisms underlying sex differences in sensitivity to the disinhibiting effects of alcohol in heavy drinkers.

The overall objective of the research is to identify hormonal determinants of alcohol effects on brain activation during response inhibition (BARI) in young adult female and male drinkers. BARI will be assessed using functional magnetic resonance imaging (fMRI) during performance of the stop signal task. This task reliably activates right-lateralized prefrontal regions implicated in inhibitory control. This study will assess BARI during IV alcohol (60mg%) and saline infusion in women during the early follicular and mid-luteal phases and in men at matched intervals.

Eligibility criteria: Inclusion Criteria:

* heavy drinking
* Alcohol Use Disorder Identification Test score above 7
* right-handed
* BMI between 19 and 26
* high school education
* fluent in English
* women must have regular menstrual cycles
* not using hormonal contraceptives

Exclusion Criteria:

* drug use disorder (SCID, DSM-5), other than nicotine or caffeine
* meets withdrawal criteria
* history of physical or psychiatric disease
* contraindication for fMRI
* pregnant or breastfeeding
* smoking more than 5 cigarettes per day

Primary outcomes:
measure: Brain Activation During Response Inhibition (BARI) - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Brain Activation During Response Inhibition (BARI) - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
Secondary outcomes:
measure: Estradiol Levels - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Estradiol Levels - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Progesterone Levels - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Progesterone Levels - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Testosterone Levels - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Testosterone Levels - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Biphasic Alcohol Effects Score - Stimulation - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Biphasic Alcohol Effects Score - Sedation - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Biphasic Alcohol Effects Scale (BAES) - Stimulation - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Biphasic Alcohol Effects Scale (BAES) - Sedation - Saline
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Drug Effects Questionnaire Score - Feel - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Drug Effects Questionnaire Score - Like - Alcohol Infusion
timeFrame: During two alcohol sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two alcohol sessions are averaged together
measure: Drug Effects Questionnaire (DEQ) - Feel - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
measure: Drug Effects Questionnaire (DEQ) - Like - Saline Infusion
timeFrame: During two saline (placebo) sessions which could occur on two of four possible days: 1 or 2 and 15 or 16; data from the two saline sessions are averaged together
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University Of Kentucky Psychology Research Lab
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Mark Fillmore, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: