Acute Alcohol Response In Bipolar Disorder: a fMRI Study

NCT04063384 | Completed Results

• 1 other identifier: K01AA027573
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime-a rate 3 to 5 times higher than what occurs in the general population. The mechanisms that contribute to elevated rates of comorbidity are not known. Early identification in individuals with bipolar disorder who are at risk for AUDs could inform novel intervention strategies and improve life-long outcomes. The primary objective of this protocol is to use alcohol administration procedures and functional MRI techniques to investigate subjective response to alcohol, compared to placebo, and relationship with functional responses of, and connectivity among, brain regions in ventral prefrontal emotional networks in young adults with bipolar disorder and healthy comparison young adults. Baseline clinical and structural MRI assessments will be completed in 30 bipolar and 30 healthy young adults (21-26 years of age, 50% women). Then, following standard beverage administration procedures, participants will complete within-person, counter-balanced, fMRI scans and complete measures of subjective response to alcohol while under the influence of alcohol or placebo. Specifically, individual differences in the experience of stimulating, sedative, and anxiolytic effects of alcohol (measured with self-report surveys) and individual differences in neural responses to alcohol within ventral prefrontal emotional networks will be investigated and differences in bipolar disorder compared to healthy participants assessed. Functional MRI scans during a continuous performance task with emotional and neutral distractors (CPT-END) and at rest will be collected while under the influence of alcohol and placebo and compared. Experience of stimulating, sedative, and anxiolytic effects of alcohol from self-report survey data and neural responses to emotional stimuli while under the influence of alcohol compared to placebo will be the primary data outcomes assessed. Additionally, associations between subjective and neural response to alcohol and drinking patterns will be explored (secondary outcomes). The primary endpoint of the study will be after completion of both alcohol and placebo beverage conditions.

Conditions

Bipolar Disorder; Alcohol Drinking; Alcohol Use Disorder

Outcome Measures

Primary Outcomes (2)

• Level of Intoxication (Subjective Response) on Each Condition Day After Drinking Relative to How They Felt When Arriving to the Lab on That Respective Day )Prior to Drinking)

  Participants fill out self-report surveys \[specifically the Subjective Effects of Alcohol Scale (SEAS)\] on how they feel when they arrive to their beverage administration sessions (alcohol and placebo sessions). They then feel out the same self-report surveys on how intoxicated they feel during their beverage sessions (alcohol and placebo). Changes in how intoxicated they feel is calculated for both the alcohol and placebo condition (compared to how they felt pre-beverage). 4 subscores are calculated by summing individual items: positive valence/positive arousal (stimulation), SEAS positive valence/negative arousal (anxiolytic), negative valence/negative arousal (aggression/agitation), and negative valence/negative arousal (sedative effects). Summed subscores on the SEAS range between 0 and 40. Change scores can therefore range between -40 and 40 (post-beverage compared to pre-beverage feelings). Scores greater than 0 on any one subscale indicates feeling more effects of alcohol.

  up to 1 week

• Change in Functional Coupling Between Regions of Interest During Viewing of Emotional Stimuli (Neural Responses While Viewing Emotional Stimuli Were Contrasted Against Neural Responses When Viewing Squares)

  Neural responses to emotional stimuli during the alcohol and placebo sessions were modeled. Fisher transformed correlation coefficients between regions of interest while viewing emotional stimuli (compared to squares) were calculated for each beverage session and data extracted for posthoc analysis. Values represent change scores in correlation coefficients during each beverage session.

  up to 1 week

Study Arms (2)

Alcohol

ACTIVE COMPARATOR

Participants will be dosed to a 0.08g% blood alcohol concentration.

Other: alcohol beverage

Placebo

PLACEBO COMPARATOR

Participants will receive a low dose of alcohol (placebo condition).

Other: Placebo beverage

Interventions

alcohol beverage OTHER

Participants will be provided alcohol during study visits and changes in behavior/neural activity after consuming alcohol will be examined.

Alcohol

Placebo beverage OTHER

placebo beverage conditions.

Placebo

Eligibility Criteria

• Age: 21 Years - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• between 21 and 26 years of age
• having consumed at least 4 (men) or 3 (women) drinks on a single occasion over the last year
• euthymic at the time of study
• \- Meeting Diagnostic and Statistical Manual-5 Research Version (DSM-V-RV) diagnostic criteria for bipolar disorder, confirmed by structured interview

You may not qualify if:

• history of significant medical illness, particularly if possible changes in cerebral tissue
• neurologic abnormality including significant head trauma (loss of consciousness of ≥5-min)
• full Scale intelligence quotient (IQ) \<85
• contraindication to MRI scanning
• positive pregnancy test
• current cannabis use disorder\>moderate
• history of severe AUDs
• scores \> 15 on the alcohol Use Disorders Identification Test (AUDIT; part of phone screen)
• ever being in an abstinence-oriented treatment program for alcohol use
• reporting wanting to quit drinking but not being able to
• any medical, religious, or other reasons for not drinking alcohol
• history of heart attack, heart trouble, high blood pressure, diabetes, or liver disease
• an adverse reaction to alcoholic beverages
• reporting never consuming 4 (men) or 3 (women) or more drinks on a single occasion over the last year
• unwillingness to have a friend or family member drive them home after the alcohol administration sessions

Sponsors & Collaborators

• University of Texas at Austin: lead

Study Sites (1)

University of Texas at Austin

Austin, Texas, 78712, United States

Location

Related Publications (4)

• Kirsch DE, Kosted R, Le V, Almeida JRC, Fromme K, Strakowski SM, Lippard ETC. Ventral prefrontal network response to alcohol in young adults with bipolar disorder: a within-subject randomized placebo-controlled alcohol administration study. Neuropsychopharmacology. 2023 Dec;48(13):1910-1919. doi: 10.1038/s41386-023-01657-6. Epub 2023 Jul 20.

  PMID: 37474761 RESULT

• Kosted R, Kirsch DE, Le V, Fromme K, Lippard ETC. Subjective response to alcohol: Interactive effects of early life stress, parental risk for mood and substance use disorders, and drinking context. Pharmacol Biochem Behav. 2023 Aug;229:173591. doi: 10.1016/j.pbb.2023.173591. Epub 2023 Jun 22.

  PMID: 37353164 RESULT

• Lippard ETC, Kirsch DE, Kosted R, Le V, Almeida JRC, Fromme K, Strakowski SM. Subjective response to alcohol in young adults with bipolar disorder and recent alcohol use: a within-subject randomized placebo-controlled alcohol administration study. Psychopharmacology (Berl). 2023 Apr;240(4):739-753. doi: 10.1007/s00213-023-06315-9. Epub 2023 Jan 25.

  PMID: 36695842 RESULT

• Kirsch DE, Le V, Kosted R, Fromme K, Lippard ETC. Neural underpinnings of expecting alcohol: Placebo alcohol administration alters nucleus accumbens resting state functional connectivity. Behav Brain Res. 2023 Feb 2;437:114148. doi: 10.1016/j.bbr.2022.114148. Epub 2022 Oct 4.

  PMID: 36206822 RESULT

MeSH Terms

Conditions

Bipolar Disorder; Alcohol Drinking; Alcoholism

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Drinking Behavior; Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Limitations and Caveats

Drinking was performed in a clinical space and lacks ecological validity (representing real world drinking environment). How individuals reported feeling may not generalize to how they feel when they consume alcohol regularly. Additionally, participants were the only one drinking. Individuals may respond differently when drinking in more social environments.

Results Point of Contact

• Title: Dr. Elizabeth Lippard
• Organization: University of Texas at Austin

elizabeth.lippard@austin.utexas.edu

512-495-5216

Study Officials

• Elizabeth Lippard, PhD

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 21, 2019
• Study Start: July 22, 2019
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: December 11, 2025
• Results First Posted: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: We will complete all our analyses and publish results and methodologies in scientific journals before the data are available to the research community. Data will be made available following 6 months after publication.
• Access Criteria: We will be collecting identifying information. Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Locations

US (1)