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Sex Differences in Risk for Alcohol Abuse

Not Applicable
Completed
Conditions
Alcohol Abuse
Interventions
Drug: Saline
Registration Number
NCT04543942
Lead Sponsor
Mark Fillmore
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Saline, then alcohol, then saline, then alcoholSalineParticipants first received saline intravenously and then 24-48 hours later they received alcohol (60mg%) intravenously. Two weeks later, they again received saline intravenously and then 24 - 48 hours later they received alcohol (60mg%) intravenously.
Alcohol, then saline, then alcohol, then salineAlcoholParticipants first received alcohol (60mg%) intravenously and then 24-48 hours later they received saline intravenously. Two weeks later, they again received alcohol (60mg%) intravenously and then 24 - 48 hours later they received saline intravenously.
Alcohol, then saline, then alcohol, then salineSalineParticipants first received alcohol (60mg%) intravenously and then 24-48 hours later they received saline intravenously. Two weeks later, they again received alcohol (60mg%) intravenously and then 24 - 48 hours later they received saline intravenously.
Saline, then alcohol, then saline, then alcoholAlcoholParticipants first received saline intravenously and then 24-48 hours later they received alcohol (60mg%) intravenously. Two weeks later, they again received saline intravenously and then 24 - 48 hours later they received alcohol (60mg%) intravenously.
Primary Outcome Measures
NameTimeMethod
Brain Activation During Response Inhibition (BARI) - Saline InfusionDuring 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

Brain activation during response inhibition (BARI) was assessed using blood oxygenation level dependent (BOLD) fMRI during performance of the stop signal task during saline infusion. Values were determined by the contrast of BOLD activation during successful inhibition trials relative to go trials.

Brain Activation During Response Inhibition (BARI) - Alcohol InfusionDuring 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

Brain activation during response inhibition (BARI) was assessed using blood oxygenation level dependent (BOLD) fMRI during performance of the stop signal task during alcohol (60mg%) infusion. Values were determined by the contrast of BOLD activation during successful inhibition trials relative to go trials.

Secondary Outcome Measures
NameTimeMethod
Estradiol Levels - Alcohol InfusionDuring 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

Estradiol levels (pg/mL) were measured from blood samples following alcohol infusion.

Estradiol Levels - Saline InfusionDuring 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

Estradiol levels (pg/mL) were measured from blood samples following saline infusion.

Progesterone Levels - Alcohol InfusionDuring 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

Progesterone levels (ng/mL) were measured from blood samples prior to alcohol infusion.

Progesterone Levels - Saline InfusionDuring 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

Progesterone levels (ng/mL) were measured from blood samples following saline infusion.

Testosterone Levels - Alcohol InfusionDuring 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

Testosterone levels (ng/dL) were measured from blood samples following alcohol infusion.

Testosterone Levels - Saline InfusionDuring 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

Testosterone levels (ng/dL) were measured from blood samples following saline infusion.

Biphasic Alcohol Effects Score - Stimulation - Alcohol InfusionDuring 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

The Biphasic Alcohol Effects Scale (BAES) is a 14-point self-reporting, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. Scores range from 0-10 for each of the 7 Stimulation sub-scale questions, for a total Stimulation score range of 0-70. Higher scores indicate increased stimulation. This outcome measure was collected during alcohol (60mg%) infusion.

Biphasic Alcohol Effects Score - Sedation - Alcohol InfusionDuring 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

The Biphasic Alcohol Effects Scale (BAES) is a 14-point self-reporting, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. Scores range from 0-10 for each of the 7 Sedation sub-scale questions, for a total Sedation score range of 0-70. Higher scores indicate increased sedation. This outcome measure was collected during alcohol (60mg%) infusion.

Biphasic Alcohol Effects Scale (BAES) - Stimulation - Saline InfusionDuring 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

The Biphasic Alcohol Effects Scale (BAES) is a 14-point self-reporting, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. Scores range from 0-10 for each of the 7 Stimulation sub-scale questions, for a total Stimulation score range of 0-70. Higher scores indicate increased stimulation. This outcome measure was collected during saline infusion.

Biphasic Alcohol Effects Scale (BAES) - Sedation - SalineDuring 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

The Biphasic Alcohol Effects Scale (BAES) is a 14-point self-reporting, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. Scores range from 0-10 for each of the 7 Sedation sub-scale questions, for a total Sedation score range of 0-70. Higher scores indicate increased stimulation. This outcome measure was collected during saline infusion.

Drug Effects Questionnaire Score - Feel - Alcohol InfusionDuring 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

The Drug Effects Questionnaire (DEQ) consists of four questions to assess acute subjective response to alcohol intake. This measure captures the amount someone feels the effects of alcohol, on a scale from 0 to 100. Higher scores indicate greater levels of 'feel alcohol'. Scores were obtained during alcohol (60mg%) infusion.

Drug Effects Questionnaire Score - Like - Alcohol InfusionDuring 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

The Drug Effects Questionnaire (DEQ) consists of four questions to assess acute subjective response to alcohol intake. This measure captures the amount someone likes the effects of alcohol, on a scale from 0 to 100. Higher scores indicate greater levels of 'like alcohol'. Scores were obtained during alcohol (60mg%) infusion.

Drug Effects Questionnaire (DEQ) - Feel - Saline InfusionDuring 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

The Drug Effects Questionnaire (DEQ) consists of four questions to assess acute subjective response to alcohol intake. This measure captures the amount someone feels the effects of alcohol, on a scale from 0 to 100. Higher scores indicate greater levels of 'feel alcohol'. Scores were obtained during saline infusion.

Drug Effects Questionnaire (DEQ) - Like - Saline InfusionDuring 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

The Drug Effects Questionnaire (DEQ) consists of four questions to assess acute subjective response to alcohol intake. This measure captures the amount someone likes the effects of alcohol, on a scale from 0 to 100. Higher scores indicate greater levels of 'like alcohol'. Scores were obtained during saline infusion.

Trial Locations

Locations (1)

University Of Kentucky Psychology Research Lab

🇺🇸

Lexington, Kentucky, United States

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