Acute Alcohol Response In Bipolar Disorder: a fMRI Study (BACS)

Subjective Response to Alcohol and Associated Neural Systems in Bipolar Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Drinking; Bipolar Disorder; Alcohol Use Disorder
• Intervention / Treatment: Other: alcohol beverage; Other: Placebo beverage

Detailed Description

A total of 60 bipolar and healthy comparison subjects (n=30 per group, 21-26 years of age, 50% women, with no history of a moderate/severe AUD) will be recruited from the greater Austin area. Once recruited and enrolled, subjects will undergo detailed structured clinical evaluations to verify inclusion and exclusion criteria, comprehensive assessment of alcohol and other drug use history, and cognitive testing, followed by structural MRI assessments. Following standard beverage administration procedures, they will then complete measures of subjective response to alcohol and fMRI scans while under the influence of alcohol or a placebo condition (counter-balanced). For each participant the first beverage session assignment (whether the participant is given alcohol or the placebo beverage first) will be randomized. Alcohol and placebo sessions will occur within 3 days of each other. FMRI assessments will include a continuous performance task with emotional and neutral distractors (CPT-END) and a resting state scan.

For both the alcohol and the placebo beverage conditions, the protocol will be the same. The beverage administration sessions will occur in a private room at the University of Texas at Austin in the Imaging Research Center. The table in the testing room will be wiped down with alcohol prior to the participant's arrival (olfactory cue). Study staff will use an algorithm to calculate individual alcohol doses based on the participants' age, sex, height, and weight. Participants fast from food for 4 hours prior to their session. Before beginning consumption of their beverages, they will eat a weight-adjusted, 1 calorie per pound snack of pretzels. While participants eat their pretzels, study staff will mix beverages in front of participants. Vodka and placebo (decarbonated tonic water) will be stored in absolute vodka bottles, measured out, and combined with mixer in front of participants. Mixed drinks will be poured into glasses that have been sitting face down with rims soaking in vodka. Prior to giving the beverage to the participant, all drinks will get an alcohol floater (squirt of absolute vodka on top of the drink). Participants will be given 20 minutes to orally consume two beverages (10 minutes per beverage).

Following oral consumption and a 10 minute absorption period, breathalyzer tests will be conducted to identify a .06g% ascending limb breath alcohol concentration (BrAC). Self-report of subjective response to alcohol will be collected and participants will immediately enter the scanner and complete the fMRI scan (acquisition parameters are identical during alcohol and placebo conditions). BrAC will be tracked after the MRI scan and subjective response to alcohol collected again at peak BrAC and at descending BrAC of .06g%. Consistent with NIAAA guidelines for human alcohol studies, BrAC readings will continue every 30 minutes until participants are below 0.04% at which time they will be escorted home. During the placebo condition, participants will be given false BrAC readings. False BrAC readings given to participants during the placebo session will be based on the average BrACs we record during the alcohol sessions. The average time participants stay in the laboratory will be the same for the placebo and alcohol beverage conditions. Participants are debriefed after completing all sessions and the need for deception to ensure the placebo-controlled alcohol session will be explained.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • University of Texas at Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 26 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Inclusion criteria for all participants:

• 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

Inclusion criteria for bipolar disorder participants:

- Meeting Diagnostic and Statistical Manual-5 Research Version (DSM-V-RV) diagnostic criteria for bipolar disorder, confirmed by structured interview

Exclusion Criteria:

For all subjects exclusion criteria include:

• 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
• a past year substance use disorder (other than alcohol, cannabis, or nicotine)

Additional exclusion criteria for bipolar disorder participants:

- not taking medications for greater than or equal to 4 weeks (i.e. participants must be stable on medications)

Additional exclusion criteria for healthy comparison subjects also include:

• any prior psychiatric hospitalizations
• lifetime history of a neurodevelopmental disorder, affective disorder, psychotic disorder, eating disorder
• greater than 1 month of lifetime psychotropic medication. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alcohol; Participants will be dosed to a 0.08g% blood alcohol concentration.	Other: alcohol beverage; Participants will be provided alcohol during study visits and changes in behavior/neural activity after consuming alcohol will be examined.
Placebo Comparator: Placebo; Participants will receive a low dose of alcohol (placebo condition).	Other: Placebo beverage; placebo beverage conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neural responses to emotional stimuli (fMRI: neural responses during alcohol session minus neural responses during placebo session)	Neural responses to emotional stimuli during the alcohol and placebo sessions will be modeled. Change in neural responses (alcohol minus placebo session) in regions of interest will be calculated. Study participation to collect data (baseline clinical assessment, alcohol and placebo MRI sessions) should not take more than 1 week.	baseline and up to 1 week
Change in behavior (self-report surveys: alcohol session minus placebo session)	Participants will fill out self-report surveys on how they feel when they arrive to their beverage administration sessions (alcohol and placebo). They will 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 will be calculated for both the alcohol and placebo condition.	baseline and up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinking patterns	Participants will complete self-report surveys describing their drinking pattern and a structured assessment (time line follow back) to assess recent quantity, duration, and frequency of drinking. Correlations between this secondary measure and primary measures listed above will be explored.	up to 3 months

Collaborators and Investigators

• Sponsor: University of Texas at Austin

Publications and helpful links

General Publications

• Lee J, Lee CW, Jang Y, You JS, Park YS, Ji E, Yu H, Oh S, Ryoo HA, Cho N, Park JY, Yoon J, Baek JH, Park HY, Ha TH, Myung W. Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial. Front Psychiatry. 2022 Sep 20;13:969199. doi: 10.3389/fpsyt.2022.969199. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 17, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Bipolar and Related Disorders; Alcohol Drinking; Alcoholism; Disease; Bipolar Disorder
• Other Study ID Numbers: K01AA027573 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After study completion and publication of finding, functional neuroimaging data and behavior data collected following alcohol and placebo conditions will be shared.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

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