Tirzepatide in MetALD

NCT07046819 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10002246002246-AA
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Use Disorder; Metabolic Alcohol-associated Liver Disease

Keywords

BMI; Weight; Alcohol; Metabolism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Saline

PLACEBO COMPARATOR

A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.

Other: Placebo

Tirzepatide

ACTIVE COMPARATOR

A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.

Tirzepatide

Placebo OTHER

A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks.

Saline

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Treatment seeking for alcohol use disorder
• History of a serious hypersensitivity reaction to GLP-1RA/GIPRA
• Current/past use of GLP-1RA/GIPRA within the last 3 months
• Clinically significant and/or unstable cardiovascular disease over the past 12 months
• History of diabetes mellitus or blood hemoglobin A1c (HbA1c) \>= 6.5 % at screening
• Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening, history of cirrhosis, esophageal varices
• Subjects with platelets count of less than 110,000/ mm\^3
• Alanine aminotransferase or aspartate aminotransferase exceeding 5 times the upper limit of normal levels at screening
• Bilirubin 2x UNL or Creatinine \> 2 mg/dL at screening
• Patients with coagulopathy defined as INR \>1.5, prothrombin time prolonged by \> 3s, and/or platelets \<75,000 / mm\^3 at screening
• Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at screening
• Chronic renal failure as estimated by glomerular filtration rate (GFR) \< 60mL/min/1.73 m\^2 at screening
• History of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• History of previous bariatric surgery or transplant surgery

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3.

  PMID: 30473097 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcoholism; Body Weight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Falk W Lohoff, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nada M Saleh

CONTACT

(301) 496-3799; nada.saleh@nih.gov

Falk W Lohoff, M.D.

CONTACT

(301) 827-1542; falk.lohoff@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 2, 2025
• Study Start: April 7, 2026
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-01-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: IPD may be available within 12-24 months of publication.
• Access Criteria: IPD may be shared via secured email. The principal investigator will review requests based on specific criteria.

Locations

US (1)