Clinical trial NCT05135767: Biobehavioral Pathways Underlying Alcohol Use and Health
Official title: Biobehavioral Pathways Underlying Alcohol Use and Health
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Use Disorder
Liver Diseases
Keywords: Alcohol Use Disorder
Liver Diseases
Craving
Ecological Momentary Assessment
Biobehavioral
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: Rhode Island Hospital
First posted: 2021-11-26
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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. 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Screen Eligible Who Enroll
timeFrame: 3 months
measure: Percentage of Participants Who Complete the Study
timeFrame: 3 months
measure: Percentage of Participants Who Withdraw
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Providence
country: United States
facility: Brown University School of Public Health
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Brown University
name: Hayley Treloar Padovano, PhD
role: PRINCIPAL_INVESTIGATOR
References: