Alcohol Abuse
Conditions
Brief summary
Prolonged alcohol use results in drinking despite resultant problems and adverse consequences. The investigators propose to test a laboratory model of human seeking despite aversion to use as an early marker of disease onset, and as a tool for study of its neural functional substrates, and identification of effective treatments.
Detailed description
The long-term goal for this project is to establish a model of alcohol seeking despite aversion (SDA) as a platform for the laboratory testing of novel pharmacologic and behavioral interventions that can be used among those with the highest risk, but who have yet to progress to treatment-resistant drinking. The objective of this application is to test SDA across multiple levels of analysis. The investigators consider SDA as an early marker of alcohol use disorder progression that is related to lifetime drinking history, alcohol use disorder risks, and brain physiology. The investigators have completed a pilot study demonstrating that SDA can be objectively quantified via an intravenous alcohol self-administration task, in which operant work for identical incremental alcohol rewards is paired with aversive stimuli. This preliminary data supports the central hypotheses that behavior in the SDA model is attributable to lifetime alcohol exposure, is related to alcohol use disorder risk factors and phenotypes, and reflects alterations in neural system function. In this project, SDA will be measured along with recent and lifetime drinking history, negative affect-based rash action (i.e. negative urgency, including action with respect to alcohol use), and self-rating of the effects of alcohol. The rationale for this work is that it would lead to the first objective, well-validated measure of SDA in humans.
Interventions
BEHAVIORALAversive Cue
Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol
BEHAVIORALNeutral Cue
Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol
Sponsors
Purdue University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Subjects are not informed which session will include aversive cues.
Intervention model description
2 session crossover, random order, single blind
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women age 21-55 * Range of lifetime alcohol drinking history from 25 kg to 500 kg, with preference for extremes, plus recent drinking at least 7 drinks/week (women) and 20 drinks/week (men) * Able to understand and complete questionnaires and procedures in English * Willing and able to tolerate iv placement * Right-handed (for fMRI Arm only)
Exclusion criteria
* Pregnant or breast-feeding * Seeking or in treatment for substance use disorder or under court ordered abstinence * Medications, medical disorders or conditions that could affect study outcome or subject safety * Positive urine drug screen for amphetamines/methamphetamines, barbiturates, benzodiazepines, cocaine, opiates, or phencyclidine * Positive breath alcohol (BrAC) reading on arrival at any study visit * Actively suicidal (within previous year) * Left-handed or ambidextrous (for fMRI Arm only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Exposure to Aversive Cues on IV Alcohol Self-administration | In two infusion sessions, to occur 5-14 days apart | Participants earn 2.5 min exposures to an increase in iv infusion rate (causing a prescribed increase in breath alcohol concentration (BRAC)) by completing repetitions of a constant attention button-pressing task (CAT). The task is designed so that the number of correct CAT trials required increases progressively from 1 (for the first drink) to 380 (for the 20th drink) on an accelerating scale. The dependent measure Breakpoint is defined as the cumulative number of correct and incorrect CAT trials completed when the last drink is earned; in the time allowed possible values ranged from 1 to 800. Effect of the Aversive cue was assessed by calculating a difference score (Breakpoint Aversive Cue-Breakpoint Neutral Cue); the range of possible difference scores was -800 to +800. A positive difference score indicates a higher breakpoint (more alcohol earned) in the Aversive Cue session; a negative number indicates a lower breakpoint (less alcohol earned). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the general public local to Indianapolis, Indiana. Recruiting methods included flyering, ads run in local publications, and word of mouth. Recruiting period ran from January, 2018 to July, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Higher Lifetime Alcohol Drinking Participants with a history of higher lifetime alcohol consumption will complete 2 IV alcohol infusion sessions that include aversive or neutral cues. | 42 |
| Lower Lifetime Alcohol Drinking Participants with a history of lower lifetime alcohol consumption will complete 2 IV alcohol infusion sessions that include aversive or neutral cues. | 45 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First IV Infusion Session | Adverse Event | 0 | 2 |
| Session 1 to Session 2 Interval | Pandemic | 0 | 1 |
| Session 2 to Imaging Interval | MRI exclusion (left handed) | 3 | 5 |
| Session 2 to Imaging Interval | Participant declined fMRI at enrollment | 8 | 11 |
Baseline characteristics
| Characteristic | Lower Lifetime Alcohol Drinking | Total | Higher Lifetime Alcohol Drinking |
|---|---|---|---|
| Age, Continuous | 30.6 Years STANDARD_DEVIATION 10.5 | 31.9 Years STANDARD_DEVIATION 10.6 | 33.3 Years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 77 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 27 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 28 Participants | 52 Participants | 24 Participants |
| Region of Enrollment United States | 44 participants | 84 participants | 40 participants |
| Sex: Female, Male Female | 22 Participants | 48 Participants | 26 Participants |
| Sex: Female, Male Male | 23 Participants | 39 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 87 | 0 / 57 |
| other Total, other adverse events | 3 / 84 | 4 / 87 | 3 / 57 |
| serious Total, serious adverse events | 0 / 84 | 0 / 87 | 0 / 57 |
Outcome results
Primary
The Effect of Exposure to Aversive Cues on IV Alcohol Self-administration
Participants earn 2.5 min exposures to an increase in iv infusion rate (causing a prescribed increase in breath alcohol concentration (BRAC)) by completing repetitions of a constant attention button-pressing task (CAT). The task is designed so that the number of correct CAT trials required increases progressively from 1 (for the first drink) to 380 (for the 20th drink) on an accelerating scale. The dependent measure Breakpoint is defined as the cumulative number of correct and incorrect CAT trials completed when the last drink is earned; in the time allowed possible values ranged from 1 to 800. Effect of the Aversive cue was assessed by calculating a difference score (Breakpoint Aversive Cue-Breakpoint Neutral Cue); the range of possible difference scores was -800 to +800. A positive difference score indicates a higher breakpoint (more alcohol earned) in the Aversive Cue session; a negative number indicates a lower breakpoint (less alcohol earned).
Time frame: In two infusion sessions, to occur 5-14 days apart
Population: Between subjects design
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Higher Lifetime Alcohol Drinking | The Effect of Exposure to Aversive Cues on IV Alcohol Self-administration | -6.0 Units on a scale | Standard Error 8.6 |
| Lower Lifetime Alcohol Drinking | The Effect of Exposure to Aversive Cues on IV Alcohol Self-administration | 7.3 Units on a scale | Standard Error 6.9 |
Comparison: 2-tailed, unpaired T-testp-value: <0.2t-test, 2 sided