Acute Alcohol Response In Bipolar Disorder: a Longitudinal Alcohol Administration/fMRI Study

NCT05838274 | Recruiting

• 1 other identifier: R01AA030038
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime and is associated with worse illness outcomes, yet few studies have been performed to clarify the causes of this comorbidity. Understanding biological risk factors that associate with and predict the development of AUDs in bipolar disorder could inform interventions and prevention efforts to reduce the rate of this comorbidity and improve outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in bipolar disorder aimed at capturing the mechanisms leading to the emergence of AUDs. Previous work in AUDs suggest that subjective responses to alcohol and stress-related mechanisms may contribute to the development of AUDs. In bipolar disorder, altered developmental trajectory of critical ventral prefrontal networks that modulate mood and reward processing may alter responses to alcohol and stressors; consequently, the disruption in typical neurodevelopment may be an underlying factor for the high rates of comorbidity. No longitudinal data exist investigating if this developmental hypothesis is correct. To address this gap, the investigators will use a multimodal neuroimaging approach, modeling structural and functional neural trajectories of corticolimbic networks over young adulthood, incorporating alcohol administration procedures, clinical phenotyping, and investigating effects of acute stress exposure and early life stress. Research aims are to identify biological risk factors-i.e., changes in subjective response to alcohol and associated neural trajectories-that are associated with the development of alcohol misuse and symptoms of AUDs over a two-year longitudinal period in young adults with bipolar disorder and typical developing young adults. Longitudinal data will be collected on 160 young adults (50% with bipolar disorder, 50% female; aged 21-26). This study is a natural extension of the PI's K01 award. How acute exposure to stress and childhood maltreatment affects subjective response to alcohol and risk for prospective alcohol misuse and symptoms of AUDs will be investigated. The investigators will test our hypothesis that developmental differences in bipolar disorder versus typical developing individuals disrupt corticolimbic networks during young adulthood, increase sensitivity to stress, and lead to changes in subjective response to alcohol and placebo response increasing risk for developing AUDs.

Conditions

Bipolar Disorder; Alcohol Drinking; Alcohol Use Disorder

Outcome Measures

Primary Outcomes (4)

• changes in subjective response

  Subjective response to alcohol will be measured with the subjective effects of alcohol scale (SEAS) at baseline and two-years later and changes in subjective response to alcohol over time (SEAS two year follow-up minus SEAS baseline) investigated and interactions with group (young adults with bipolar disorder, typical comparison young adults) modeled.

  2 years

• Neural trajectories associated with subjective response to alcohol

  Changes in neural trajectories over the two-year follow-up period will be modeled and relations with subjective response at two-year follow-up investigated. We will model changes in cortical thickness and surface area of frontolimbic regions of interest and investigate if these neural trajectories relate to changes in subjective response to alcohol (measured with the SEAS at baseline and follow-up).

  2 years

• Relations between changes in subjective response and associated neural trajectories with alcohol use disorder symptoms at two-year follow-up

  Changes in subjective response (measured with the SEAS) and neural trajectories over the follow up period (changes in cortical thickness and surface area of frontlimbic regions of interest) and relations with alcohol problems at two-year follow up will be modeled with number of alcohol use disorder symptoms on the SCID at two-year follow up as the dependent variable.

  2 years

• Relations between changes in subjective response and associated neural trajectories with alcohol misuse and problems at two-year follow-up

  Changes in subjective response (measured with the SEAS) and neural trajectories over the follow up period (changes in cortical thickness and surface area of frontolimbic regions of interest) and relations with alcohol problems at two-year follow up will be modeled with AUDIT score at two-year follow up as the dependent variable.

  2 years

Study Arms (2)

Alcohol

ACTIVE COMPARATOR

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

Other: Alcohol vs. Placebo beverage conditions

Placebo

PLACEBO COMPARATOR

placebo beverage condition

Other: Alcohol vs. Placebo beverage conditions

Interventions

Alcohol vs. Placebo beverage conditions OTHER

Individuals will drink beverages containing alcohol. How they respond to a high vs. low dose will be compared.

Alcohol; 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 enrollment
• \- 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

RECRUITING

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

Study Officials

• Elizabeth Lippard, PhD

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Coordinator

CONTACT

5124955198; behavioral.neuroimaging@austin.utexas.edu

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: Associate Professor

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: May 1, 2023
• Study Start: July 11, 2023
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: January 12, 2026

Record last verified: 2026-01

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)