Study of Tirzepatide for Recovery and Alcohol Use Management

Phase 2RecruitingNCT06727331

Brigham and Women's Hospital20 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Alcohol Use Disorder (AUD)

Interventions

TirzepatideDRUG

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.

Saline PlaceboOTHER

Placebo syringes of saline and matching volume will be produced by IDS.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Brigham and Women's Hospital

Boston, Massachusetts, United States

ACTIVE_NOT_RECRUITING

Brigham and Women's Faulkner Hospital

Jamaica Plain, Massachusetts, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 3-6).

Secondary Outcomes

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.

Time frame: At each study visit up to and including the final visit 5 weeks after baseline.

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.

Time frame: 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.

Central Contacts

Joji Suzuki, MD

CONTACT

617-732-5752 jsuzuki2@bwh.harvard.edu

Laura M Holsen, Ph.D.

CONTACT

617-525-8772 lholsen@bwh.harvard.edu

Data from ClinicalTrials.gov

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