Human Alcohol Seeking Despite Aversion

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.

Study Overview

• Status: Terminated
• Conditions: Alcohol Abuse
• Intervention / Treatment: Behavioral: Aversive Cue; Behavioral: Neutral Cue

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher lifetime alcohol drinking; Participants with a history of higher lifetime alcohol consumption	Behavioral: Aversive Cue; Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol; Behavioral: Neutral Cue; Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol
Experimental: Lower lifetime alcohol drinking; Participants with a lower lifetime alcohol consumption	Behavioral: Aversive Cue; Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol; Behavioral: Neutral Cue; Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	In two infusion sessions, to occur 5-14 days apart

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Purdue University
• Investigators: Principal Investigator: Martin H Plawecki, MD, PhD, Psychiatry, Indiana University School of Medicine; Principal Investigator: Melissa A Cyders, PhD, Psychology, Indiana University-Purdue University at Indianapolis

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism
• Other Study ID Numbers: 1709318986; P60AA007611 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After publication of the main findings, a de-identified dataset will be made available through direct requests as described above; a statement to this effect will be included in all published manuscripts.

The current proposal utilizes the Seeking Despite Aversion Task, a newly developed Computer-Assisted Infusion System (CAIS) protocol that integrates delivery of visual stimuli into the Constant Attention Task and optical markers for evoked response potential generation. This task, like other CAIS protocols, will become part of the portfolio of CAIS programs that our lab makes available to other scientists once our specific funded use of this protocol is completed. Modified versions of this protocol could be provided to other investigators prior to completion of this project as long as these projects do not directly compete.

• IPD Sharing Time Frame: Data will become available following final publication of all manuscripts by the component investigators. Earliest date is estimated to be January, 2025.

IPD Sharing Access Criteria

Data and Resource Sharing Plan - Indiana Alcohol Research Center (IARC)

Consistent with its past history, the IARC continues to make available its data and resources to investigators engaged in alcoholism research outside of Indiana University. Detailed procedures are available on request. In brief, investigators must submit a written request specifying in adequate detail the specific resource(s) required and a study protocol indicating the specific aims, scientific rationale, methods and procedure, and analysis of results; a signed IARC Resource Utilization Agreement Form; and for studies involving human subjects, Institutional Review Board (IRB) approval if needed for the proposed study. The request will be reviewed by the IARC Steering Committee. Investigators must agree to acknowledge the Indiana Alcohol Research Center (P60 AA007611) as the source of the resource in all resulting publications.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No