Study of Tirzepatide for Recovery and Alcohol Use Management (STREAM)

Tirzepatide for the Treatment of Alcohol Use Disorder: A Pilot Randomized Controlled Trial

This is a pilot, 4-week, double-blind, placebo-controlled, randomized trial of individuals with alcohol use disorder (AUD) to receive weekly injections of either tirzepatide (n=10) or matching placebo (n=10). The primary aim is to determine the effects of tirzepatide on cue-reactivity among individuals with AUD. The secondary aim is to assess the safety and preliminary efficacy of tirzepatide for AUD.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder (AUD)
• Intervention / Treatment: Drug: Tirzepatide; Other: Saline Placebo

Detailed Description

Participants include N=20 men and women with DSM5 diagnosis of AUD. Potential participants will be screened and enrolled only if they meet full inclusion criteria. After screening and baseline procedures (Visit 1) are complete, participants will be randomized to receive either tirzepatide or placebo. Following randomization, participants will be scheduled for five study visits (Visits 2-6). Each visit will last approximately 1 hour, except for study visits 1 and 6 which will take no more than 3 hours in order to conduct additional neurocognitive testing, including cue-induced cravings and decision-making tests. At all study visits, participants will complete vital signs, weight, urine toxicology testing, a blood draw for glucose, and questionnaires probing secondary outcomes (i.e. anxiety and depression, suicidality, substance use, opioid withdrawal symptoms, cravings, etc). At study visits 2-5, the weekly dose of tirzepatide or placebo will be administered, and assessment of adverse events will also be completed. Both participants and study staff (including raters) will be blinded to active drug vs. placebo. At visit 1, subjects' expectations about their potential treatment will be queried. The final visit, visit 6, also called the follow-up visit, will also assess subjects' guess as to which treatment they received. The medication will be purchased from the manufacturer and stored by IDS. The IDS will extract the tirzepatide and draw the dose into syringes, which will match visually with the placebo doses.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joji Suzuki, MD; Phone Number: 617-732-5752; Email: jsuzuki2@bwh.harvard.edu
• Study Contact Backup: Name: Laura M Holsen, Ph.D.; Phone Number: 617-525-8772; Email: lholsen@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Active, not recruiting
      • Brigham and Women's Hospital
    • Jamaica Plain, Massachusetts, United States, 02130
      • Recruiting
      • Brigham and Women's Faulkner Hospital
      • Contact: Joji Suzuki, MD; Phone Number: 617-732-5752; Email: jsuzuki2@bwh.harvard.edu
      • Principal Investigator: Joji Suzuki, MD
      • Contact: Jeong Hoo (Eric) Lee, MD; Email: jlee351@bwh.harvard.edu
      • Sub-Investigator: Jeong Hoo (Eric) Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English speaking adults aged 18 and above
• Diagnosed with current DSM-5 alcohol use disorder
• Willing and able to physically travel to BWH CCI outpatient facilities for study visits

Exclusion Criteria:

• CIWA score at screening ≥ 8.
• Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
• Any lifetime diagnosis of eating disorders including anorexia, bulimia, binge eating, or avoidant/restrictive food intake disorder
• BMI<23 mg/kg2
• Current or lifetime diagnosis of Type 1 or Type 2 diabetes
• Current (or within 30 days of enrollment) use of any anti-obesity medications or medications with glucose lowering properties (including GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors)
• Use of any GLP-1 agonist medications in the prior 3 months
• Anticipating receipt of any other GLP-1 agonist medications during the trial
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• Current hypoglycemia as indicated by a blood sugar level of ≤70 mg/dL measured at the baseline visit
• Calcitonin ≥ 50 ng/L
• Triglycerides ≥500 mg/dL
• Untreated cholelithiasis or gallbladder disease
• Acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or congestive heart failure in the last 90 days
• Uncontrolled hypertension at baseline, as indicated by an average blood pressure reading of >180/110 after three successive readings
• History of inflammatory bowel disease, bariatric surgery, pancreatitis, diabetic gastroparesis, or non-arteritic anterior ischemic optic neuropathy
• Liver function test greater than 5 times upper normal limit
• Renal impairment as indicated by eGFR of <30
• History of hypersensitivity or allergy to tirzepatide
• Pregnant or breastfeeding
• Anticipated to be enrolled in another clinical drug trial during participation in this trial
• Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide; This arm will receive tirzepatide (n=10) weekly 2.5mg injections for 4 weeks.	Drug: Tirzepatide; This intervention will consist of the FDA-approved dosing schedule. Participants will receive 2.5mg weekly injections for 4 weeks. IDS will extract tirzepatide and draw the doses into syringes.; Other Names: Mounjaro
Placebo Comparator: Saline Placebo; This arm will receive saline placebo injections (n=10) weekly for 4 weeks.	Other: Saline Placebo; Placebo syringes of saline and matching volume will be produced by IDS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-induced Cravings for Alcohol	Cue-induced craving scores at follow-up compared to baseline using a standard cue-reactivity paradigm utilizing visual cues. Cravings will be measured on a scale from 0-10 with 10 meaning extreme cravings.	Baseline visit and 5 weeks after baseline visit.
Incidence and Severity of Adverse Events	Study staff will be notified of any hospital admissions via Epic, and adverse events will be queried specifically using the Patient Rated Inventory of Side Effects (PRISE) at study weeks 2-5. The PRISE is a self-report tool to qualify side effects. For each domain, the patient indicates whether they have experienced certain symptoms and whether the symptoms are tolerable or distressing.	Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 3-6).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monetary Choice Questionnaire (MCQ)	A self-report tool used to measure delayed discounting. Participants will be asked to pick one of the two choices given. Score calculated typically falls between 0.0 and 0.5, with smaller values indicating a lack of discounting and preference for delayed rewards and higher values indicating strong discounting and a preference for immediate rewards.	Baseline visit and 5 weeks after baseline visit.
Visual Probe Task	A behavioral task to assess attentional bias. Alcohol-related and neutral images will be used, different from the ones used for the cue-reactivity paradigm to limit habituation. A pair of images will appear on the left and right of the screen for either a short (200ms) or long (500ms) stimulus duration to assess automatic orientating and controlled attention processing, respectively. Image pairs will be replaced by a probe in the location of either the opioid-related or neutral image. The probe will remain until the participant responds to identify the probe orientation by pressing the response keys as quickly as possible. This task will yield reaction times for analysis.	Baseline visit and 5 weeks after baseline visit.
Clinical Institute Withdrawal Assessment (CIWA)	Tool for assessing alcohol withdrawal. Scale of 0-67, with a higher number meaning more severe withdrawal.	At each study visit up to and including the final visit 5 weeks after baseline.
Blood Sugar	Blood glucose obtained via finger stick or blood already drawn for other tests.	At each study visit up to and including the final visit 5 weeks after baseline.
Hemoglobin A1c	Hemoglobin A1c obtained via blood draw.	Baseline and 5 weeks after baseline visit.
Weight	Weight measured in kilograms.	At each study visit up to and including the final visit 5 weeks after baseline.
Heart rate	Heart rate measured in beats per minute.	At each study visit up to and including the final visit 5 weeks after baseline.
Blood pressure	Blood pressure measured in systolic/diastolic (mmHg/mmHg). mmHg = millimeters of mercury.	At each study visit up to and including the final visit 5 weeks after baseline.
Assessment of Blind	Measure of participant perception of whether they received the active study drug.	5 weeks after baseline visit.
Stanford Efficacy of Treatment Scale (SETS)	A tool for measuring patient outcome expectancy in clinical trials.	Baseline visit.
Penn Alcohol Craving Scale (PACS)	A self-report tool used to measure craving for alcohol during the past week. Participants respond to 5 questions on a scale of 0-6 for a total score of 0-30, with higher scores indicating stronger cravings.	At each study visit up to and including the final visit 5 weeks after baseline.
Percent days abstinent	The percentage of days abstinent from alcohol, defined as 0 drinks on a given day, out of all days queried. The study investigators will use the Time-Line Follow Back (TLFB), a gold-standard method of evaluating substance use, as well as weekly urine toxicology screens.	At each study visit up to and including the final visit 5 weeks after baseline.
Percent heavy drinking days	Percentage of heavy drinking days, defined as 5 or more drinks in one day for males and 4 or more drinks in one day for females, out of all days queried. The study investigators will use the Time-Line Follow Back (TLFB), a gold-standard method of evaluating substance use, as well as weekly urine toxicology screens.	At each study visit up to and including the final visit 5 weeks after baseline.
Drinks per drinking day	The average number of drinks per drinking day. A drinking day is a day in which one or more alcoholic beverages were consumed. The study investigators will use the Time-Line Follow Back (TLFB), a gold-standard method of evaluating substance use, as well as weekly urine toxicology screens.	At each study visit up to and including the final visit 5 weeks after baseline.
Columbia Suicide Severity Rating Scale (C-SSRS)	A commonly used tool to assess suicidal ideation. The sum ranges from 2 to 25, with the higher number indicating more intense ideation.	At each study visit up to and including the final visit 5 weeks after baseline.
Patient Health Questionnaire-8 (PHQ-8)	A tool to assess depression symptoms. Scale of 0-24, with a higher score meaning more depression symptoms.	At each study visit up to and including the final visit 5 weeks after baseline.
Generalized Anxiety Disorder-7 (GAD-7)	A standard tool to assess anxiety symptoms. Scale of 0-21 with a higher number indicating more anxiety.	At each study visit up to and including the final visit 5 weeks after baseline.
Fibrosis-4 (FIB-4)	A non-invasive measure of liver fibrosis. The higher the score, the more severe the fibrosis.	Baseline visit and 5 weeks after baseline visit.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Joji Suzuki, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 2024P003497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No