Biobehavioral Pathways Underlying Alcohol Use and Health

Alcohol Use Disorder Clinical Trial

Official title:

Biobehavioral Pathways Underlying Alcohol Use and Health

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05135767
• Other study ID #: 2011002840
• Secondary ID: P20GM130414
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 28, 2022
• Est. completion date: November 30, 2023

Study information

• Verified date: October 2023
• Source: Brown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are intersecting diseases that add substantially to the global burden of disease and mortality. ALD refers to a spectrum of liver tissue injury caused by chronic and excessive alcohol use. Although reducing drinking is a main treatment goal, this is often unachievable for many patients with ALD due to an underlying AUD characterized by alcohol craving and drinking despite harms. While numerous, high-quality studies demonstrate effectiveness of brief psychosocial interventions for AUD, few trials have tested the efficacy of psychosocial interventions to reduce drinking in individuals with or at risk for ALD. This project establishes a team of addiction scientists and hepatologists to form a partnership and support future collaboration.

Description:

The long-term goal of this research program is to develop more effective behavioral interventions to halt the progression of alcohol-associated liver disease (ALD) by addressing at-risk drinking patterns and alcohol use disorder (AUD). The investigators originally proposed a prospective, two-arm intervention study comparing individuals with ALD and AUD vs. those with AUD and without a prior history of ALD or current blood biomarkers suggestive of ALD (target N = 44; n = 22 per group). The proposed project was designed to demonstrate the feasibility of implementing a brief motivational intervention targeting drinking for patients with ALD recruited from specialty gastroenterology clinics. To keep pace with the original overall recruitment targets within the confines of an adjusted award period, the approach was modified to continue recruiting individuals with AUD and at risk for ALD from the community beyond the original balanced sample size for this group.

After clinic and community recruitment, screening, and enrollment, participants complete four weeks of digital health self-monitoring of precursors of drinking in real-world settings, paired blood biomarkers of liver function, inflammation, and immune response collected prior to the behavioral intervention, at 3 weeks, and at 3-month follow-up. After the first week of self-monitoring, participants attend an in-person research visit involving questionnaires, a laboratory alcohol-cue-reactivity task, and receive a 60-minute, video-conference brief motivational intervention with personalized feedback from self-monitoring reports completed via smartphones in daily life and liver-health biomarkers. The intervention is followed by three weekly research visits culminating with a 30-minute booster video-conference intervention with personalized feedback and exit interviews. A final, in-person research visit is completed at 3 months to evaluate post-intervention, near-term outcomes.

Primarily, this project aims to establish our team and collect initial feasibility and acceptability data for a full-scale clinical trial evaluating biobehavioral endophenotypes AUD in individuals at risk for or with chronic liver disease. At-risk drinking is studied in the setting of a brief intervention designed to enhance knowledge of liver-health risk factors, identify personal precursors of drinking, and increase motivation for sustained change. Secondarily, this project aims to test whether biobehavioral endophenotypes associated with alcohol-use outcomes in clinical trials can serve as indicators of AUD treatment response among individuals at risk for or with ALD. Biomarkers of inflammation and immune activation are explored as mechanisms of persistence of endophenotypes, specifically levels of pro-inflammatory cytokines, chemokines, and others implicated in the pathogenesis of ALD. All study procedures and intervention are offered in English and Spanish, preparing for future full-scale clinical intervention trials among monolingual Spanish-speaking individuals.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: November 30, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

General Inclusion Criteria. To be eligible, the interested volunteer must:

1. Be at least 18 years of age.

2. Meet the Diagnostic and Statistical Manual-5 criteria for alcohol use disorder, indicated by meeting 2 or more symptom criteria.

3. If male, report 14 or more standard alcoholic drinks per week, or if female, report 7 or more standard alcoholic drinks per week at any point in the 90 days prior to enrollment.

4. Be able to speak and read English or Spanish in order to provide written informed consent and understand written and oral instructions in English or Spanish.

General Exclusion Criteria. Interested volunteers must not have any of the following:

1. Meet the Diagnostic and Statistical Manual-5 criteria for a current diagnosis of psychotic disorders.

2. Currently receiving specialized psychosocial treatment for an alcohol-use or drug problem.

3. If female, pregnant or nursing.

4. Be anyone who, in the opinion of the investigative team, could not currently be safely withdrawn from alcohol without medical detoxification.

5. A BMI of 40 or more, or 35 or more and experiencing obesity-related health conditions, such as high blood pressure or diabetes.

6. Known medical conditions that, in the opinion of the investigative team, would confound results (e.g., uncontrolled infections, multiorgan failure, uncontrolled upper gastrointestinal bleeding, hepatocellular carcinoma or other active malignancies except skin cancer).

7. Patients who have received a liver transplant or are too ill to participate.

8. Pre-existing loss of kidney function with estimated glomerular filtration rate < 30.

9. Any other condition that, in the opinion of the investigative team, would make the interested volunteer unsuitable for the study or unable to comply with the requirements.

Additional Inclusion Criteria for the ALD + AUD Arm.

To be eligible in the ALD+AUD group, the interested volunteer must be diagnosed with advanced alcohol-associated liver disease (i.e., either alcoholic hepatitis or alcoholic cirrhosis). ALD will be determined by chart review. Interested volunteers must have one of the following:

1. Positive liver biopsy, or

2. Fibroscan® score > 12.5, or

3. Evidence of a nodular liver or portal hypertension on abdominal imaging, or

4. Presence of portal hypertensive complications such as hepatic encephalopathy, ascites, or varices, or

5. Fibrosis-4 index >= 3.25, or

6. Aspartate transaminase-platelet ratio index >= 1.0.

Additional Exclusion Criteria for the AUD-only Arm. To be eligible in the AUD-only group, the interested volunteer must not show the following diagnostic test results indicating advanced, alcoholic fibrosis >=F3.

1. Fibrosis-4 index >= 3.25*, or

2. Aspartate transaminase-platelet ratio index >= 1.0**, or

3. Gamma-glutamyl transpeptidase-to-platelet ratio >= 0.32.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Liver Diseases

Intervention

Behavioral:
• Brief Motivational Interviewing with Personalized Feedback
A brief motivational interviewing (MI) intervention will target drinking. The intervention will leverage in-depth personalized feedback to identify areas of progress and barriers to change. The personalized feedback will include results of laboratory diagnostic tests, summary reports of timeline followback interviews, and graphical depictions of self-monitoring reports collected on smartphones in daily life. The brief intervention will include an initial 60-minute videoconference session, two brief, 5-10 minute phone-call check-ins completed one and two weeks after the initial intervention, and a 30-minute videoconference booster session completed three weeks after the initial intervention.

Locations

Country	Name	City	State
United States	Brown University School of Public Health	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island

Sponsors (3)

Lead Sponsor	Collaborator
Brown University	National Institute of General Medical Sciences (NIGMS), Rhode Island Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Enrolled Per Month	Feasibility will be evaluated through the pace of recruitment, i.e., the number participants recruited per month. The target is two participants enrolling in the study per month.	24 months
Primary	Percentage of Screen Eligible Who Enroll	Feasibility will be evaluated through the percentage of those who are screened as eligible for the study who enroll as participants in the study. The target enrollment rate is greater than or equal to 60% of screen eligible.	24 months
Primary	Percentage of Participants Who Complete the Study	Feasibility will be evaluated through the percentage of those participants who are enrolled in the study who complete the study. The target retention rate is greater than or equal to 70% of enrolled participants.	24 months
Primary	Percentage of Participants Who Withdraw	Acceptability will be evaluated through the percentage of those participants who enroll in the study who withdraw from the study. A participant is considered to have withdrawn from the study if they indicate that they no longer wish to be a part of the study (i.e., not lost to contact). The target withdrawal rate is less than or equal to 20% of enrolled participants.	24 months
Secondary	Craving in Daily Life	Ecological momentary assessment (EMA) is a method for collecting self-monitoring data using smartphones. Participants will complete smartphone reports for a total of 4 weeks including a 1-week screening phase and 3-week intervention phase.Participants will self-monitor and rate the intensity of their alcohol craving in daily life. They will also indicate situational and contextual factors, including the presence of visible alcohol cues. Craving will be assessed using a visual analogue scale from 0 to 10 via the question, "How strong is your craving to drink alcohol right now?".	4 weeks
Secondary	Craving in the Human Laboratory	Participants will be exposed to alcohol and water cues in the human laboratory via a standardized in vivo cue reactivity paradigm. The participant's typical alcoholic beverage is used as the in vivo alcohol cue. Each cue exposure lasts approximately 90 seconds. An initial relaxation period is followed by exposure to the water cue, and two repeated exposures to the alcohol cue. To match assessment of craving in daily life, craving will be assessed using a visual analogue scale from 0 to 10 via the question, "How strong is your craving to drink alcohol right now?". Craving will also be assessed with the Alcohol Craving Questionnaire--Short Form-Revised, a 12-item self-administered, multidimensional state measure of acute alcohol craving.	20 minutes