Clinical trial NCT05191446: Coronavirus Disease 2019 (Covid-19) Impact on Alcohol-related Liver Disease Patient Outcomes, Care and Alcohol Use
Official title: Impact of the Coronavirus 2019 (COVID-19) Pandemic on Patient Outcomes, Telehealth Care Delivery, and Treatment for Unhealthy Alcohol Use in Vulnerable Patients With Advanced Liver Disease Across Two Healthcare Systems
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Liver Diseases
Alcohol Use Disorder
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2022-01-13
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized trial with patients assigned to an experimental condition or to usual care.
Primary purpose: TREATMENT

Brief summary: The study consists of a randomized controlled trial evaluating the efficacy and feasibility of a stepped alcohol treatment using telemedicine on unhealthy alcohol use in patients with chronic liver disease receiving care in hepatology practices at three sites. Patients who meet eligibility criteria will be randomized to one of two study arms: 1) Stepped Alcohol Treatment (SAT) or, 2) Usual Care (UC). Participants will be randomized separately by site. SAT includes 3 sessions of motivational interviewing followed by referral to addiction medicine for patients who do not reduce unhealthy drinking. Trial outcome measures will be complete at 6 and 12 months following baseline enrollment.

Detailed description: Background/Rationale: Unhealthy alcohol use is consumption of alcohol at more than the "moderate" levels of up to 1 drink per day (7/week) for women and up to 2 drinks per day (14/week) for men, as defined by NIAAA. Unhealthy alcohol use is prevalent in chronic liver disease (CLD), and for many patients no level of alcohol could be considered safe. Guidelines recommend integrated multidisciplinary care, but evidence-based strategies to address alcohol use beyond brief counseling are rarely provided in hepatology practices. A recent study showed that most veterans with cirrhosis and coexisting AUD do not receive behavioral treatment or pharmacotherapy for AUD. Similarly, in a study of cirrhosis patients \[\~70% alcohol-associated liver disease (ALD)\] hospitalized at 4 safety net hospitals, less than half reported abstinence from alcohol, while 39% reported daily alcohol use, and alcoholic hepatitis accounted for the highest in-hospital mortality compared to other comorbidities. The investigators are focusing on these important outcomes in this study. Current guidelines recommend that brief intervention, pharmacotherapy, and referral to treatment should be offered to patients with ALD including those with alcohol use disorder (AUD) or advanced CLD of any etiology who drink alcohol at more than moderate amounts. Our approach follows these guidelines.

Overall approach: The investigators will enroll a total of 180 patients (90 assigned to stepped care, 90 to usual care) with liver disease and alcohol use; 60 patients will be recruited from each of the three study sites (two Veterans Administrations Healthcare System sites in Palo Alto and San Francisco as well as a safety net public clinic in San Francisco, CA). This intent-to-treat outcome study will include all patients recruited, whether or not they complete the interventions.

Recruitment: Hepatology practices at all three sites routinely screen patients for alcohol use. Eligible patients will be identified using the electronic medical record and, following permission from their provider, patients will be contacted about the study. Patients may also be referred directly by their hepatology providers. Interested patients who meet all eligibility criteria will be consented to participate in the study. The investigators will include English and Spanish speakers using bicultural and bilingual clinical research coordinators. Following enrollment, participants will have baseline, 3-, 6-, and 12-month assessments. Participants will be offered $50 for completing the baseline, 3-, and 6-month, and $100 for 12-month assessments.

Baseline assessment: At baseline, patient demographics (age, sex, race/ethnicity, income, education, insurance), medical history, medications, etiology of CLD, presence of cirrhosis or hepatic decompensation, history of illicit drugs, laboratory tests of liver function and COVID-19 will be captured using the electronic medical record. Measures of alcohol use will be performed using validated measures. Patients will then undergo randomization.

Randomization to study arms: Patients who meet study criteria will be randomized to one of two study arms: 1) Stepped Alcohol Treatment (SAT) or, 2) Usual Care (UC). See "Arms and Interventions" section for details.

Follow-up Assessments: A research staff member not participating in patient care will conduct follow-up interviews. He/she will be blinded to participants' treatment condition. Participants will be contacted by telephone at 3, 6 and 12 months to complete the measures. Patient reporting via telephone follow-up has been reliable in prior studies but a biomarker of alcohol use will also be performed to validate reports of alcohol abstinence

Statistical analysis: Repeated measures analyses will be conducted within a generalized linear mixed model (GLMM) framework. These models accommodate the range of continuous, count, and discrete outcomes that will be measured. Analyses will include treatment condition (SAT vs UC) as a between-subjects effect. Time (baseline, 3-month, 6-month, and 12-months) will be a repeated effect and the treatment x time interaction will be examined. Analyses will account for clustering of patients within study site.

Sample size: Sample size was determined using data from prior studies of MI and stepped care interventions for unhealthy alcohol use in individuals with liver disease and other populations, for the primary outcome (less than moderate alcohol use) and the secondary outcome of drinks per week.

Anticipated results: The investigators anticipate that SAT participants will be more likely than UC to reduce or be abstinent from alcohol use at the 3-, 6- and 12-month follow-up. The investigators also anticipate that SAT participants will have better clinical outcomes (less new or worsening clinical decompensation or hospitalizations) than controls at follow-up. The investigators will also explore COVID-19 related outcomes in both arms, e.g., infection rates, hospitalization and clinical outcomes.

Eligibility criteria: Inclusion criteria:

1. Men and women age ≥ 18 years.
2. Diagnosis of chronic liver disease (CLD).
3. Unhealthy alcohol use, defined as more than moderate amount of alcohol use within the prior 30 days by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria defined as on average more than 1 drink/day (7 drinks per week) for women and more than 2 drinks per day (14 drinks per week) for men, or on average at least one heavy drinking day (4+ drinks in a day for women and 5+ for men) per week in the prior 30 days. A standard drink is \~14 g of alcohol.
4. Ability to access a telephone or a digital device (i.e., computer, tablet or smart phone).

Exclusion criteria:

1. Severe medical or psychiatric conditions or evidence of acute alcohol intoxication preventing participation in the study
2. Are currently enrolled in formal treatment for unhealthy alcohol use, excluding self or mutual-help groups (e.g., Alcoholics Anonymous).
3. Women who are pregnant or breastfeeding or unwilling to use birth control.
4. Language preference other than English, Spanish or Chinese.
5. Unwilling or unable to provide informed consent.

Primary outcomes:
measure: Change in alcohol use
timeFrame: 6 months after enrollment
Secondary outcomes:
measure: Alcohol use cessation
timeFrame: 6 and 12 months after enrollment
measure: Drinks per week
timeFrame: 6 and 12 months after enrollment
measure: Liver-related outcomes
timeFrame: 6 and 12 months after enrollment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of california San Francisco
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Mandana Khalili, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Satre DD, Dasarathy D, Batki SL, Ostacher MJ, Snyder HR, Hua W, Parekh P, Shui AM, Cheung R, Monto A, Wong RJ, Chen JY, Liao M, Tana M, Chen PH, Haight CG, Fakadej T, Khalili M. Factors Associated With Motivation to Reduce Alcohol Use Among Patients With Chronic Liver Disease. Aliment Pharmacol Ther. 2025 Feb;61(3):481-490. doi: 10.1111/apt.18387. Epub 2024 Nov 11.
citation: Luk JW, Ha NB, Shui AM, Snyder HR, Batki SL, Ostacher MJ, Monto A, Wong RJ, Cheung R, Parekh P, Hua W, Tompkins DA, Fakadej T, Haight CG, Liao M, Khalili M, Satre DD. Demographic and clinical characteristics associated with utilization of alcohol use disorder treatment in a multicenter study of patients with alcohol-associated cirrhosis. Alcohol Clin Exp Res (Hoboken). 2025 Jan;49(1):244-255. doi: 10.1111/acer.15500. Epub 2024 Dec 4.
citation: Wong RJ, Yang Z, Ostacher M, Zhang W, Satre D, Monto A, Khalili M, Singal AK, Cheung R. Alcohol Use Patterns During and After the COVID-19 Pandemic Among Veterans in the United States. Am J Med. 2024 Mar;137(3):236-239.e2. doi: 10.1016/j.amjmed.2023.11.013. Epub 2023 Dec 3.
citation: Athavale P, Wong RJ, Satre DD, Monto A, Cheung R, Chen JY, Batki SL, Ostacher MJ, Snyder HR, Widiarto BD, Oh SY, Liao M, Viviani AML, Khalili M. Telehepatology Use and Satisfaction Among Vulnerable Cirrhosis Patients Across Three Healthcare Systems in the Coronavirus Disease Pandemic Era. Gastro Hep Adv. 2023 Nov 20;3(2):201-209. doi: 10.1016/j.gastha.2023.11.006. eCollection 2024.
citation: Luk JW, Satre DD, Cheung R, Wong RJ, Monto A, Chen JY, Batki SL, Ostacher MJ, Snyder HR, Shui AM, Liao M, Haight CG, Khalili M. Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis. Hepatol Commun. 2024 Feb 3;8(2):e0379. doi: 10.1097/HC9.0000000000000379. eCollection 2024 Feb 1.
citation: Kim RG, Patel S, Satre DD, Shumway M, Chen JY, Magee C, Wong RJ, Monto A, Cheung R, Khalili M. Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease. Dig Dis Sci. 2024 Mar;69(3):732-742. doi: 10.1007/s10620-023-08222-7. Epub 2024 Jan 13.