Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD)
2 other identifiers
interventional
176
1 country
1
Brief 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: Tirzepatide is injected under the skin. Participants will get an injection once a week for 2 to 6 weeks. These injections will include up to 3 doses of study drug and 3 doses of a placebo. The placebo looks like the study drug but does not have any medicine. They will not know which they are receiving. Participants with AUD will have 4 to 6 positron emission tomography and magnetic resonance imaging combined scans (PET/MRI). For each scan a radioactive substance (tracer) will be given through a tube inserted into a vein. Participants will lie on a table that slides into a cylinder. They will wear a device on their head to measure brain activity. They will perform tasks on a screen. Before 1 scan, they will receive a stimulant drug (Ritalin). Each scan will take about 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. Healthy volunteers will have 2 or 3 PET/MRI scans. They will receive Ritalin before 1 of them. They will not receive the study drug.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2026
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 29, 2026
CompletedFirst Posted
Study publicly available on registry
April 30, 2026
CompletedStudy Start
First participant enrolled
May 11, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2031
Study Completion
Last participant's last visit for all outcomes
December 31, 2031
May 6, 2026
April 23, 2026
5.6 years
April 29, 2026
May 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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. We will look at the effects of methylphenidate on brain dopamine. We will also look at brain responses, mood and thinking. The results of each subject's scans will be compared to each other. We will also compare the results to other participants to see if we get similar information.
We aim to have each subject (n=5) complete all study procedures within 60 days.
Part 2 (n=88, 44 healthy volunteers and 44 AUD) : Effects of Tirzepatide on striatal dopamine D1R and D2R availability; striatal DA increase; brain reactivity to MP and to food and alcohol cues in AUD and in healthy controls.
We will measure dopamine levels 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. We will look at the effects of methylphenidate on brain dopamine. To do this we will obtain imaging scans after the subject receives Tirzepatide and a Placebo. We will also look at brain responses, mood and thinking. Results from the same scans on two separate days will be compared to each other. We will also compare the results to other participants to see if we get similar information.
We aim to have each subject complete study procedures within 90 days, but this could take longer. AUD participants will undergo a Follow Up phone call about 1 month after imaging scans are complete.
Secondary Outcomes (2)
Part 1: Subjective responses to MP
We aim to have each subject (n=5) complete all study procedures within 60 days.
Part 2: Examine Tirzepatide s effects on subjective effects to MP,sleep, alcohol craving (AUD only), alcohol withdrawal symptoms (AUD only), food craving, locomotor activity, mood and weight.
We aim to have each subject complete study procedures within 90 days, but this could take longer. AUD participants will undergo a Follow Up phone call about 1 month after imaging scans are complete.
Study Arms (5)
[11C]NNC-112 - Part 2
PLACEBO COMPARATOR\[11C\]NNC-112 PET/MR or PET/CT scan obtained without any drug intervention to measure dopamine D1 receptors.
[11C]raclopride plus drug - Part 1
ACTIVE COMPARATORRadiotracer 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]raclopride plus drug - Part 2
ACTIVE COMPARATORRadiotracer 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 - Part 2
PLACEBO COMPARATOR1st 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.
Tirzepatide - Part 2
ACTIVE COMPARATOR1st 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.
Interventions
Drug approved for diabetes administered SQ. Subject is blind to drug.
Placebo will be normal saline administered SQ. Subject is blind to 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 PET/MR or PET/CT scan obtained without any drug intervention to measure dopamine D1 receptors.
Eligibility Criteria
You may qualify if:
- Healthy Volunteer Participants
- To be eligible to participate in this study, an individual must meet the following criteria:
- Enrollment in 14AA0181.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, ages 21-65 years old.
- Ability to understand and willingness to sign a written informed consent document.
- Have or had any prior experience with stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, or prescription stimulants (prescription or recreational use), whether or not they have had a past substance use disorder.
- AUD Participants
- To be eligible, individuals with AUD must meet the following criteria:
- Enrollment in 14AA0181.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, ages 21-65 years old.
- Ability to understand and willingness to sign a written informed consent document.
- DSM 5 diagnosis of mild to moderate AUD.
- Have or had any prior experience with stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, or prescription stimulants (prescription or recreational use), whether or not they have had a past substance use disorder.
- +3 more criteria
You may not qualify if:
- All Participants (Healthy Volunteers and AUD)
- Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI
- Cannot lie comfortably flat on his/her back for up to 2 hours in the PET/MRI scanner.
- BMI \<23 or \>35 (but no more than 500 lbs). The PET/MRI scanner bed is tested to a weight limit of 500 lbs.
- Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam.
- Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 55 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study (i.e., within 24 hours before study procedures). Females must not be currently breastfeeding.
- Women using oral contraceptives (Part 2 of study). Women of childbearing age who are taking oral contraceptives will be required to switch to a non-oral hormonal contraceptive method (ie implants, injections, or IUDs) or add a barrier method (condoms) for the duration of the study and for 4 weeks after the last dose of study drug after explaining to them that Tirzepatide could make contraceptive less effective. We will not provide nonoral contraceptive medications to participants.
- Severe head trauma with loss of consciousness \> 60 minutes
- Current severe mental illness (schizophrenia, bipolar disorder).
- Montgomery-Asberg depression rating scale (MADRS) total score \> 35 or suicidal thoughts item score \> 3, indicating severe depression or moderate suicidality, respectively.
- Thyroid cancer or family history of thyroid cancer or personal or family history of multiple endocrine neoplasia syndrome type-2 (MEN-2).
- History for cerebral aneurysm.
- Past or present history of chest pain and trouble breathing with activity.
- History of Heart Disease, Hypertension or Cardiovascular disorders.
- History of seizures, anxiety, panic attacks, psychosis or glaucoma which are contraindicated with receiving methylphenidate.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nora D Volkow Adler, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 29, 2026
First Posted
April 30, 2026
Study Start (Estimated)
May 11, 2026
Primary Completion (Estimated)
December 31, 2031
Study Completion (Estimated)
December 31, 2031
Last Updated
May 6, 2026
Record last verified: 2026-04-23