Study of Tirzepatide for Recovery and Alcohol Use Management

Official title

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

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.

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.

Interventions

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

Primary outcome measures

• Cue-induced Cravings for Alcohol [Time frame: Baseline visit and 5 weeks after baseline visit.]
• Incidence and Severity of Adverse Events [Time frame: Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 3-6).]

Secondary outcome measures (12)

• Penn Alcohol Craving Scale (PACS) [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Monetary Choice Questionnaire (MCQ) [Time frame: Baseline visit and 5 weeks after baseline visit.]
• Visual Probe Task [Time frame: Baseline visit and 5 weeks after baseline visit.]
• Percent days abstinent [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Percent heavy drinking days [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Drinks per drinking day [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Clinical Institute Withdrawal Assessment (CIWA) [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Blood Sugar [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Hemoglobin A1c [Time frame: Baseline and 5 weeks after baseline visit.]
• Weight [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Columbia Suicide Severity Rating Scale (C-SSRS) [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]
• Patient Health Questionnaire-8 (PHQ-8) [Time frame: At each study visit up to and including the final visit 5 weeks after baseline.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Brigham and Women's Hospital — Boston
• Brigham and Women's Faulkner Hospital — Jamaica Plain

Identifiers

NCT: NCT06727331 · 2024P003497

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗