Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD)

Study Summary

Background: Glucagon-like peptide 1 (GLP-1) agonist drugs are used to treat diabetes and aid weight loss. They may also help reduce cravings for drugs and alcohol. Researchers want to know if a GLP-1 drug (tirzepatide) can lessen the urge to drink in people with alcohol use disorder (AUD). Objective: To learn how the brains of people with AUD respond to a GLP-1 drug. Eligibility: People aged 21 to 65 years with AUD who are non-treatment seeking. They must be enrolled in protocol 14-AA-0181. Healthy volunteers are also needed. Design: This study consists of Part 1 and Part 2. Part 1 (Imaging Procedures): Five healthy volunteers will undergo 2 to 3 combined positron emission tomography/magnetic resonance imaging (PET/MRI) scans, with an interval of 2 to 3 weeks between scans. For each scan, a radioactive substance (tracer) will be administered intravenously. Participants will undergo PET/MRI scanning to assess brain activity during resting state. Methylphenidate (Ritalin) will be administered during each scan. Each imaging session will last approximately 2 hours. Tirzepatide and placebo will not be administered in Part 1. Participants with alcohol use disorder (AUD) are not included in Part 1. The purpose of this part of the study is to assess test/retest reproducibility of the PET/MRI combined scan measures. Part 2 (Randomization to Tirzepatide \& Placebo): Participants will be randomized to receive either Tirzepatide or Placebo first. Healthy Volunteers and AUD participants will receive both treatments in a crossover design. Tirzepatide and placebo will be administered via subcutaneous injection (under the skin) once weekly for 2 to 3 weeks. This treatment period will be followed by 2 to 3 PET/MRI combined imaging scans described in the next paragraph. After a washout interval of approximately 2 to 3 weeks, participants will cross over to the alternate treatment (tirzepatide or placebo), administered once weekly for 2 to 3 weeks. This second treatment perio

Primary Outcome

We will measure dopamine in the brain. Dopamine is a chemical messenger that carries signals between brain cells. It plays a role in human behavior. It is also believed to play a role in addiction. In this study, we will use a combined scanner for PET and MRI to measure dopamine with the stimulant drug methylphenidate. Each scan will be done by getting a small amount of a radiotracer through an IV catheter. During each of the two PET/MRI scan sessions each subject will receive IV methylphenidate

Interventions

• DRUG Placebo
• DRUG Tirzepatide
• DRUG [11C]raclopride plus drug
• DRUG [11C]NNC-112