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

Bipolar Disorder Clinical Trial

— Long_BACS  

Official title:

Biological Risk Factors for the Prospective Development of Alcohol Use Disorders in Young Adults With Bipolar Disorder and Typically Developing Young Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05838274
• Other study ID #: R01AA030038
• Status: Recruiting
• Phase: N/A
• Start date: July 11, 2023
• Est. completion date: March 31, 2028

Study information

• Verified date: December 2023
• Source: University of Texas at Austin
• Contact: Research Coordinator
• Phone: 5124955198
• Email: behavioral.neuroimaging[@]austin.utexas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The PI is currently investigating subjective response to alcohol in bipolar disorder and typical developing young adults (n=60; 50% with bipolar disorder) using placebo-controlled alcohol administration with baseline structural/functional MRI assessments collected with her K01. The proposed work will extend this active study to enroll 100 new young adults (50% with bipolar disorder) to complete baseline clinical, MRI, and placebo-controlled alcohol administration sessions. The PI's K01 is focused on investigating differences in subjective and neural response to alcohol between bipolar disorder and typical developing young adults. The proposed study will focus on investigating changes in subjective response to alcohol, placebo response, and relations with neural trajectories, the role(s) of stress, and prediction of alcohol problems over a two-year period. Longitudinal follow-up (clinical, detailed assessment of alcohol use, and MRI) will occur on average 1- and 2-years following enrollment. Participants enrolled on the PI's K01 will be brought back for longitudinal assessments to reach N=80 per group with longitudinal data (50% female; aged 21-26)]. At 2-year follow-up, placebo-controlled alcohol administration sessions will be repeated to test if sensitivity to alcohol changes over time-and if change in sensitivity to alcohol is associated with progressive neural changes in corticolimbic brain networks during young adulthood-and associations with alcohol use and symptoms of AUDs over time, and interactions with bipolar disorder. Changes in placebo-response and if changes are predictive of increased alcohol use and symptoms of AUDs will also be modeled. At one-year follow-up, a subset of participants will be invited to complete a psychosocial stress and neutral fMRI task on separate days (counter balanced; n=40 per group). Participants will immediately complete an alcohol session following the fMRI tasks and stress-induced changes in subjective response to alcohol and interactions with group will be modeled.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 31, 2028
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 26 Years

Eligibility

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 enrollment

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Bipolar Disorder

Intervention

Other:
• Alcohol vs. Placebo beverage conditions
Individuals will drink beverages containing alcohol. How they respond to a high vs. low dose will be compared.

Locations

Country	Name	City	State
United States	University of Texas at Austin	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas at Austin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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