Tirzepatide in MetALD

Not Applicable

Not yet recruiting

• Conditions: Metabolic Alcohol-associated Liver Disease; Alcohol Use Disorder
• Interventions: Other: Placebo; Drug: Tirzepatide

• Registration Number: NCT07046819
• Lead Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Brief Summary

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.

Detailed Description

STUDY DESCRIPTION:

The GLP-1/GIP receptor dual agonist tirzepatide has been recently shown to reduce HbA1c in adults with Type 2 diabetes, achieve weight reduction in adults with obesity and reduce metabolic dysfunction associated steatohepatitis. In addition, some data suggest beneficial effects on drinking behaviors. This study will evaluate the efficacy and safety of tirzepatide as a novel treatment for alcohol use disorder (AUD) and metabolic alcohol-associated liver disease (MetALD).

We hypothesize that tirzepatide will be well tolerated and safe in this new target population and that tirzepatide will achieve reduction in alcohol use, metabolic improvement and attenuate alcohol-induced liver steatosis.

OBJECTIVES:

Primary Objective:

The primary objective is to assess the efficacy of tirzepatide in individuals with AUD/MetALD.

Secondary/Exploratory Objectives:

Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage, inflammation, neuropsychiatric outcomes, drinking behaviors, epigenetic age acceleration, brain metabolites, and safety.

ENDPOINTS:

Primary endpoints:

\- co-primary endpoint: metabolic improvement from baseline as measured by percentage reduction of body weight and reduction in liver steatosis from baseline as measured by percentage reduction in Fibroscan controlled attenuation parameter (CAP) score.

Secondary endpoints:

* Reduction in liver steatosis from baseline as measured by MRI spectroscopy

* Reduction in MRI visceral fat from baseline

* Reduction in liver enzymes (ALT, AST, GGT) from baseline

* Reduction in drinking behaviors/cravings from baseline

* Reduction in one WHO risk drinking level

Secondary safety endpoints:

\- Safety and tolerability

Exploratory endpoints:

* Effects on biomarkers (i.e. Il-6, FGF21, epigenetic and genetic markers, proteomics, metabolomics)

* Effects on depression and anxiety measures

* Effects on epigenetic age acceleration

* Changes in brain metabolites as measured by MRI spectroscopy

* Changes in resting state functional connectivity

Study Timeline

• Study First Submitted: 2025-07-01
• Study First Submitted QC: 2025-07-01
• Study First Posted: 2025-07-02
• Status Verified: 2025-07-10
• Last Update Submitted: 2025-10-08
• Last Update Posted: 2025-10-09
• Study Start: 2025-10-14
• Primary Completion: 2026-07-30
• Study Completion: 2026-07-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Saline	Placebo	A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.
Tirzepatide	Tirzepatide	A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Metabolic improvement from baseline as measured by percentage reduction of body weight and reduction in liver steatosis from baseline as measured by percentage reduction in Fibroscan controlled attenuation parameter (CAP) score.	Change from baseline to week 12

Secondary Outcome Measures

Name	Time	Method
Reduction from baseline in - 1) Liver steatosis as measured by MRI spectroscopy, 2) MRI visceral fat, 3) Liver enzymes (ALT, AST, GGT), 4) Drinking behaviors/cravings, 5) WHO risk drinking level	Change from baseline to week 12

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States