Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD)

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study ID
NCT07559500
Phase
PHASE1
Status
Recruiting
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Conditions

  • Alcohol Use Disorder (AUD)

Eligibility Criteria

Sex
ALL
Age
21 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Tirzepatide — DRUG
    Drug approved for diabetes administered SQ. Subject is blind to drug.
  • Placebo — DRUG
    Placebo will be normal saline administered SQ. Subject is blind to drug.
  • [11C]raclopride plus drug — DRUG
    Radiotracer injection of \[11C\]raclopride during combined PET/MR scan to measure striatal dopamine release (Methylphenidate 0.25 mg/kg injected 45 minutes post radiotracer injection). Subject is not blind to this drug during scan.
  • [11C]NNC-112 — DRUG
    \[11C\]NNC-112 PET/MR or PET/CT scan obtained without any drug intervention to measure dopamine D1 receptors.

Study Details

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 period will be followed by an additional 2 to 3 PET/MRI scans. Participants may receive up to 3 doses of tirzepatide and 3 doses of placebo. Part 2 (Imaging Procedures): Healthy Volunteers and participants with an AUD will undergo PET/MRI scans at two time points: following tirzepatide administration and following placebo administration. For each scan a radioactive substance (tracer) will be administered intravenously. Brain activity will be measured during PET/MRI acquisition during resting state. Methylphenidate will be administered during 1 of the scans at each time point. Each imaging session will last approximately 2 hours. Participants will wear a device to track their activity for at least 1 week before each set of scans. They will have tests of their thinking, memory, and attention.

Key Dates

Start date
May 20, 2026
Status verified
May 2026
Primary completion
Dec 31, 2031
Completion
Dec 31, 2031

Study Design

Enrollment
176 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Placebo Comparator: [11C]NNC-112 - Part 2
    \[11C\]NNC-112 PET/MR or PET/CT scan obtained without any drug intervention to measure dopamine D1 receptors.
  • Active Comparator: [11C]raclopride plus drug - Part 1
    Radiotracer injection of \[11C\]raclopride during combined PET/MR scan to measure striatal dopamine release (Methylphenidate 0.25 mg/kg injected 45 minutes post radiotracer injection). Subject is not blind to this drug during scan.
  • Active Comparator: [11C]raclopride plus drug - Part 2
    Radiotracer injection of \[11C\]raclopride during combined PET/MR scan to measure striatal dopamine release (Methylphenidate 0.25 mg/kg injected 45 minutes post radiotracer injection). Subject is not blind to this drug during scan.
  • Placebo Comparator: Placebo - Part 2
    1st Dose: placebo will be administered to the abdomen.2nd Dose: placebo will be administered to the abdomen. 3rd Dose (if needed): placebo will be administered to the abdomen.Subject is blinded to drug.
  • Active Comparator: Tirzepatide - Part 2
    1st Dose: Tirpezatide (2.5 mg dose) will be administered to the abdomen.2nd Dose: Tirzepatide (5 mg dose) will be administered to the abdomen. 3rd Dose (if needed): Tirzepatide (5 mg dose) will be administered to the abdomen.Subject is blinded to drug.

Primary Outcome Measure

Part 1 (n=5 healthy volunteers): We will assess the reproducibility of striatal dopamine (DA) measures in response to iv methylphenidate (MP) using PET/MR combined scanning and the bolus infusion protocol in healthy controls. [ Time Frame: We aim to have each subject (n=5) complete all study procedures within 60 days. ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
NIH Clinical Center Office of Patient Recruitment (OPR)
[email protected]
800-411-1222

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