Randomized Controlled Trial of Tirzepatide for Methamphetamine Use Disorder (T-STEM)

This is a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial evaluating the tolerability, safety, and preliminary efficacy of tirzepatide for the treatment of individuals with moderate or severe MtUD. The central hypothesis of the proposed research is that tirzepatide is a safe and potentially efficacious treatment of MtUD.

Participants will undergo study procedures over 32 weeks, including:

1. completing self-assessments
2. undergo brief physical and review of medical and psychiatric history
3. provide urine and blood samples
4. medical management sessions
5. weekly subcutaneous study medication injections

Study Overview

• Status: Not yet recruiting
• Conditions: Methamphetamine Use Disorder
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo (saline)

Detailed Description

Methamphetamine use disorder (MtUD) affects over 1.5 million U.S. adults annually and has no FDA-approved treatments. Preclinical studies and observational data suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce stimulant use. Tirzepatide, a dual GLP-1/glucose-dependent insulinotropic peptide (GIP) receptor agonist approved for type 2 diabetes and weight management, has not been evaluated for MtUD in an adequately-powered randomized controlled trial. This Phase 2 double-blind, randomized controlled trial will enroll 228 adults with moderate or severe MtUD to receive weekly subcutaneous tirzepatide (2.5 mg/week titrated to 15 mg/week or maximally tolerated dose) or placebo for 26 weeks, followed by 6 weeks of follow-up. Safety will be monitored throughout.

The study aims are to: (1) assess tolerability (treatment discontinuation) and safety (serious adverse events) of tirzepatide; and (2) evaluate preliminary efficacy, including reduction in methamphetamine use (Timeline Follow-back), treatment response (≥6 of 8 UDS negative in weeks 23-26), and early remission (no longer meeting DSM-5 criteria at week 26). Secondary/exploratory aims include assessing reductions in methamphetamine craving and cravings for other substances.

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elizabeth Dedrick, BS; Phone Number: 469-602-2356; Email: elizabeth.dedrick@utsouthwestern.edu
• Study Contact Backup: Name: Shavonna Williams; Phone Number: 469-602-1926; Email: shavonna.williams@utsouthwestern.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90032
      • University of Southern California (USC)
      • Contact: Jimena Estrada; Phone Number: 386-846-6139; Email: jimenaes@usc.edu
    • San Francisco, California, United States, 94102
      • Center of Substance Use and Health
      • Contact: Xochitl Luna Marti; Phone Number: 628-217-6235; Email: xochitl.lunamarti@sfdph.org
      • Contact: Samantha Serrano; Email: samantha.serrano@sfdph.org
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Oklahoma State University (OSU) Center for Health Services
      • Contact: Katie Thompson, BS; Phone Number: 603-978-2208; Email: kthompson@okstate.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• be aged 18 to 65 years;
• have moderate or severe methamphetamine use disorder;
• have active pattern of methamphetamine use;
• be interested in reducing or stopping methamphetamine use;
• be able and willing to provide informed consent, comply with all study procedures, and adhere to weekly study medication injections;
• be overweight or obese (body mass index ≥25 kg/m²); and
• (only for biological females) agree to use acceptable contraception and undergo urine pregnancy testing unless unable to become pregnant

Exclusion Criteria:

• report using any glucagon like peptide 1 receptor agonists (GLP-1RA, including tirzepatide), sulfonylureas, or insulin in the past 90 days;
• have a current eating disorder or severe alcohol or substance use disorder;
• have personal or family history of medullary thyroid carcinoma, history of multiple endocrine neoplasia type 2, or hypersensitivity, angioedema, or anaphylaxis to GLP-1RAs or tirzepatide;
• have Stage 3 or higher chronic kidney disease, inadequately controlled diabetes, history of diabetic retinopathy, any unstable or serious medical or psychiatric condition, or any other reason or clinical condition that may either interfere with study participation or make the study participation unsafe (per investigator judgement);
• are currently pregnant, breastfeeding, or planning pregnancy;
• have received an investigational drug within 30 days of informed consent;
• require psychiatric hospitalization;
• have recent suicidal or current homicidal ideation;
• are incarcerated or in court-mandated residential placement;
• have unsafe use of alcohol, benzodiazepines, sedative/hypnotics, or other substances; or
• have use of concurrent medications that may pose safety risks or interfere with study procedures.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide; Eligible participants who are enrolled will receive once-weekly subcutaneous injections of tirzepatide for a 26-week period.	Drug: Tirzepatide; Eligible participants who are randomized to treatment group will receive once-weekly subcutaneous injections of tirzepatide for a 26-week period. Tirzepatide will start at 2.5 mg/week with planned dose increases every four weeks in 2.5 mg/week increments up to a maximum of 15 mg/week (or the maximally tolerated dose).; Other Names: Mounjaro; Zepbound
Placebo Comparator: Placebo (Saline); Eligible participants who are enrolled will receive once-weekly subcutaneous injections of saline for a 26-week period.	Drug: Placebo (saline); Eligible participants who are randomized to placebo group will receive once-weekly subcutaneous injections of saline for a 26-week period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response	Proportion of participants who attain treatment response (≥6 of 8 urine drug screens (UDS) negative for methamphetamine in Weeks 23 to 26).	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability - stopping of treatment	Proportion of participants discontinuing or stopping treatment before Week 26 visit.	26 weeks
Current craving for methamphetamine	Severity score (range: 0-70) on stimulant craving questionnaire, higher score reflects more severe craving.	27 weeks
Early remission	Proportion of participants no longer meeting DSM-5 criteria for at least 3 months (criterion for craving permitted) at the Week 27 visit.	27 weeks
Safety - occurrence of serious adverse event	Proportion of participants with the occurrence of serious adverse event any time on or after Week 1 visit that is deemed to be related to study drug.	26 weeks
Reduction in self-reported use of methamphetamine	From first day of Week 1 to last day of Week 26, participant's use of methamphetamine will be recorded as a binary variable (yes/no), and compared across the two treatment arms.	26 weeks
Worst past-week craving for methamphetamine	Visual analog scale (VAS) for drug craving for methamphetamine, rated on 0-100, higher score indicates more severe craving	27 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Manish Jha, MBBS, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: September 11, 2026
• First Submitted That Met QC Criteria: September 11, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; methamphetamine; substance use; MUD; tirzepatide; methamphetamine use disorder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Amino Acids, Peptides, and Proteins; Proteins; Inorganic Chemicals; Chlorine Compounds; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Sodium Compounds; Chlorides; Hydrochloric Acid; Tirzepatide; Sodium Chloride
• Other Study ID Numbers: STU20260467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD data will be shared based on NIH Policy of Data Management and Sharing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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.: Yes