A Randomized, Double-Blind, Placebo-Controlled, Flexible Dose Phase 2 Study of Efficacy and Safety of Tirzepatide in Individuals With Alcohol Use Disorder and Metabolic Alcohol-associated Liver Disease
Background: People with alcohol use disorder (AUD) often develop metabolic alcohol-associated liver disease (MetALD). MetALD is a term for the heart, liver, obesity, and other issues that can accompany AUD. MetALD can be fatal. An approved weight management drug (Tirzepatide) may be able to help people with AUD and MetALD control their alcohol intake.
Objective: To test Tirzepatide in people with AUD and MetALD.
Eligibility: People aged 21 years and older with AUD and MetALD.
Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They will have a Fibroscan: This test uses ultrasound to measure how stiff the liver is. They will answer questions about their alcohol drinking, eating habits, and mental health. Participants may opt to have imaging scans of their brain and liver. These tests will be repeated in a baseline visit. This visit will take up to 6 hours. Tirzepatide is injected under the skin once a week for 12 weeks. Participants will visit the clinic to receive each injection. Some participants will get a placebo. A placebo is given just like a Tirzepatide injection but contains no medicine. The physical exam and other tests will be repeated during clinic visits. The Fibroscan will be repeated every 2 weeks during the study. Each weekly visit will take up to 3 hours. All tests will be repeated on the last visit. These tests will include the imaging scans and Fibroscan. Participants will learn about treatment options for AUD; they will be given recommendations on ways to reduce alcohol intake. This visit will take up to 6 hours.
∙ To be eligible to participate in this study, an individual must meet all of the following criteria:
• Age 21 or older
• Ability to provide written informed consent
• Females: Negative urine pregnancy test, not currently breastfeeding, agree to abstain or use accepted form of contraception including use of oral contraceptives and an additional barrier method of contraceptive such as condoms; use of an approved IUD or other longacting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s)
• Males: Agree to abstain or use accepted form of contraception, such as condoms.
• Diagnosis of AUD as confirmed by MINI
• Current alcohol use as assessed via the TLFB (\>14 standard drinks per week for males and \>7 standard drinks per week for females on average for the last 8 weeks)
• Liver steatosis as determined by Fibroscan (CAP score \>240) at screening
• BMI \>= 25 and \<40 kg/m\^2
• metALD as defined by at least one out of 5 criteria at screening:
‣ BMI \>= 25 and \<40 kg/m\^2
⁃ Fasting serum glucose \>= 5.6mmol/L \[100mg/dL\] or HbA1c \>=5.7%
⁃ Blood pressure \>=130/85 or specific antihypertensive drug treatment
⁃ Plasma triglycerides \>=1.70mmol/L \[150mg/dL\] or lipid lowering treatment
⁃ Plasma HDL-cholesterol less than 1.0mmol/L \[40mg/dL\] or lipid lowering treatment