Study of Tirzepatide for Recovery and Alcohol Use Management

Phase 2

Not yet recruiting

• Conditions: Alcohol Use Disorder (AUD)
• Interventions: Drug: Tirzepatide; Other: Saline Placebo

• Registration Number: NCT06727331
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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.

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 (Visits 1 and 2) are complete, participants will be randomized to receive either tirzepatide or placebo. Following randomization, participants will be scheduled for five study visits (Visits 3-7). Each visit will last approximately 1 hour, except for study visits 2 and 7 which will take no more than 3 hours in order to conduct additional neurocognitive testing, including cue-induced cravings and decision-making tests. At visits 2-7, 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 3-6, 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 2, subjects' expectations about their potential treatment will be queried. The final visit, visit 7, 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 Timeline

• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-06
• Study First Posted: 2024-12-10
• Status Verified: 2025-05
• Study Start: 2025-05
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-22
• Primary Completion: 2026-05
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• English speaking adults aged 18 and above
• Admitted to the inpatient withdrawal management at Brigham and Women's Faulkner Hospital (BWF) Addiction Recovery Program (ARP) for the treatment of alcohol withdrawal.
• Diagnosed with current DSM-5 alcohol use disorder
• Willing and able to physically travel to BWH CCI outpatient facilities for study visits after discharge from the BWF ARP.

Exclusion Criteria

• DSM-5 diagnosis of any current substance use disorder excluding alcohol, cannabis or tobacco
• 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<25mg/kg2
• Current or lifetime diagnosis of Type 1 or Type 2 diabetes
• Current (or within 30 days of enrollment) use of any medications for AUD (naltrexone, acamprosate, disulfiram, gabapentin, etc.), 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
• History of or current hypoglycemia as indicated by blood sugar levels of ≤70 mg/dL
• Calcitonin ≥ 50 ng/L
• Triglycerides ≥500 mg/dL
• Untreated cholelithiasis or gallbladder disease
• History of or current angina pectoris, coronary heart disease, congestive heart failure, inflammatory bowel disease, chronic obstructive pulmonary 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 <60
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirzepatide	Tirzepatide	This arm will receive tirzepatide (n=10) weekly 2.5mg injections for 4 weeks.
Saline Placebo	Saline Placebo	This arm will receive saline placebo injections (n=10) weekly for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Cue-induced Cravings for Alcohol	Baseline visit and 5 weeks after baseline visit.	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.
Incidence and Severity of Adverse Events	Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 4-7).	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.

Secondary Outcome Measures

Name	Time	Method
Blood pressure	At each study visit up to and including the final visit 5 weeks after baseline.	Blood pressure measured in systolic/diastolic (mmHg/mmHg). mmHg = millimeters of mercury.
Assessment of Blind	5 weeks after baseline visit.	Measure of participant perception of whether they received the active study drug.
Stanford Efficacy of Treatment Scale (SETS)	Baseline visit.	A tool for measuring patient outcome expectancy in clinical trials.
Fibrosis-4 (FIB-4)	Screening visit and 5 weeks after baseline visit.	A non-invasive measure of liver fibrosis. The higher the score, the more severe the fibrosis.
Heart rate	At each study visit up to and including the final visit 5 weeks after baseline.	Heart rate measured in beats per minute.
Penn Alcohol Craving Scale (PACS)	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	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.
Monetary Choice Questionnaire (MCQ)	Baseline visit and 5 weeks after baseline visit.	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.
Visual Probe Task	Baseline visit and 5 weeks after baseline visit.	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.
Percent days abstinent	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	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.
Percent heavy drinking days	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	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.
Drinks per drinking day	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	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.
Iowa Gambling Task (IGT)	Baseline visit and 5 weeks after baseline visit.	A computerized task to measure risky decision making using four decks of cards (A, B, C, D). Participants are instructed to maximize profits. Cards from decks A and B earn more profits but lead to even higher occasional losses leading to net long-term losses, while decks C and D yield low profits but only low occasional losses resulting in a net long-term profit. The task will yield scores which are the sums of cards selected from decks A/B and decks C/D.
Clinical Institute Withdrawal Assessment (CIWA)	At each study visit up to and including the final visit 5 weeks after baseline.	Tool for assessing alcohol withdrawal. Scale of 0-67, with a higher number meaning more severe withdrawal.
Blood Sugar	At each study visit up to and including the final visit 5 weeks after baseline.	Blood glucose obtained via finger stick or blood already drawn for other tests.
Hemoglobin A1c	Baseline and 5 weeks after baseline visit.	Hemoglobin A1c obtained via blood draw.
Weight	At each study visit up to and including the final visit 5 weeks after baseline.	Weight measured in kilograms.
Columbia Suicide Severity Rating Scale (C-SSRS)	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	A commonly used tool to assess suicidal ideation. The sum ranges from 2 to 25, with the higher number indicating more intense ideation.
Patient Health Questionnaire-8 (PHQ-8)	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	A tool to assess depression symptoms. Scale of 0-24, with a higher score meaning more depression symptoms.
Generalized Anxiety Disorder-7 (GAD-7)	At each study visit except for screening up to and including the final visit 5 weeks after baseline.	A standard tool to assess anxiety symptoms. Scale of 0-21 with a higher number indicating more anxiety.
WHO Quality of Life (WHOQOL-BREF)	Baseline and 5 weeks after baseline visit.	A 26-item quality of life scale. Split into 5 domain scores: Overall Quality of Life and General Health (2-10), Physical Health (7-35), Psychological (6-30), Social relationships (3-15), and Environment (8-40). Higher scores indicate a higher quality of life.
Temporal Experience of Pleasure Scale (TEPS)	Baseline and 5 weeks after baseline visit.	A tool to assess both anticipatory and consummatory reward. 18-item tool where each item is ranked from 1 ('very false for me') to 6 ('very true for me'). Items are averaged, with higher score indicate a stronger tendency to anticipate or experience pleasure.

Trial Locations

Locations (2)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Faulkner Hospital; 🇺🇸 Jamaica Plain, Massachusetts, United States