An Open-Label Tirzepatide Trial for Comorbid Obesity and Stimulant Use Disorder

This is a phase two, open-label study to evaluate the feasibility and preliminary efficacy of using tirzepatide when prescribed for its United States (US) Food and Drug Administration (FDA) approved weight-related indication as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 1) 30 kg/m2 or greater (obesity) or 2) 27kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease) in individuals with comorbid moderate/severe methamphetamine, cocaine, or prescription stimulant use disorder. The study will screen up to 45 individuals and enroll up to N=30 individuals with moderate/severe methamphetamine, cocaine or prescription stimulant use disorder who meet FDA-approved weight-related indication of tirzepatide for a 20-week-long, once-weekly treatment with tirzepatide (dose optimized for each individual, with a minimum of 5mg/week after week-4) that will be followed by an observational follow-up period (Weeks 24, 28 and 32) after the last dose of tirzepatide. In addition, all participants will undergo magnetic resonance imaging (MRI), including structural and functional (fMRI) scans, at screening and baseline, as well as at Weeks 6, 20, 24, 28, and 32, for a total of seven scans over the course of the trial. The screening scan may be completed same day as the screening visit or scheduled on another day based on scanner availability. Participants will also receive 12 weekly contingency management (CM) in conjunction with cognitive behavioral therapy (CBT) during the 12 weeks. These combined measures will provide us with a comprehensive evaluation of tirzepatide and its potential impact on behavior and brain function/patterns in individuals with moderate/severe methamphetamine, cocaine, and stimulant use disorder.