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

NCT07693608 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: STU-2026-0206
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This open label pilot study will assess the feasibility and preliminary efficacy of tirzepatide which will be prescribed under its FDA approved weight management indication in adults with moderate or severe methamphetamine, cocaine or prescription stimulant use disorder (MUD) who also meet criteria for obesity or overweight with comorbidities. Up to 30 participants will receive 20 weeks of once weekly tirzepatide, followed by an observational follow up period. The study also incorporates MRI at seven time points to explore neural biomarkers associated with treatment response. All participants will receive 12 weeks of contingency management (CM) combined with cognitive behavioral therapy (CBT). Together, these pharmacologic, neuroimaging, and behavioral components will evaluate tirzepatide's potential to improve health and substance use outcomes in individuals with MUD.

Conditions

Obesity; Methamphetamine Use Disorder; Cocaine Use Disorder; Stimulant Use Disorders

Keywords

Methamphetamine; Cocaine; Stimulants; MUD; Overweight; Obesity; Tirzepatide; Weight management; MRI

Outcome Measures

Primary Outcomes (1)

• Effect of tirzepatide on self-reported use of stimulants

  Self-reported use of stimulants will be assessed through Timeline Followback. The Timeline Followback procedure will be used to elicit the participant's self-reported use of illicit substances, including but not limited to stimulants, and polysubstance use starting at the Screening Visit and continuing throughout study participation. During the Screening Visit, this form will be used to assess illicit use of substances for the 30-day period prior to written consent. During the study, TLFB will be administered to document the participant's self-reported use of illicit substances, nicotine, and tobacco for each visit since the previous TLFB assessment. Participant's drug of choice will be asked and determined by study coordinator and recorded along with the TLFB assessment.

  32 weeks

Secondary Outcomes (4)

• Changes in body mass index from baseline to the end of the 20-week treatment phase

  20 weeks

• Feasibility of using tirzepatide in individuals with Stimulant Use Disorder

  20 weeks

• Changes in High-sensitivity C-reative protein (hs-CRP) levels from baseline to the end of the 20-week treatment phase

  20 weeks

• Changes in gastrointestinal symptom severity from baseline until the end of the 20-week treatment phase

  20 weeks

Study Arms (1)

Arm/Group

EXPERIMENTAL

Eligible participants who are enrolled will receive once-weekly subcutaneous injections of tirzepatide for a 20-week period in accordance with FDA-prescribing label guidelines.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Following the instructions of the FDA-approved prescribing label, participants will receive the tirzepatide injection subcutaneously in either the abdomen, thigh, or upper arm once weekly for 20 weeks total. Following the instructions of the FDA-approved prescribing label, the dosing schedule will include a 4-week titration at a starting dosage of 2.5mg/week. After four weeks, dosage will be increased in 2.5mg increments, per prescribing label for tirzepatide. The recommended maintenance dosages per prescribing label are 5/mg/week, 10mg/week, or 15mg/week injected subcutaneously. Maximum dosage (up to 10mg/week) will be optimized for each individual. The 20-week treatment period will include initial 4-week of 2.5mg/week, followed by 16-week long once-weekly treatment with tirzepatide at a minimum dose of 5 mg/week (higher doses up to 10 mg/week as tolerated), that will be followed by an observational follow-up period every 4 weeks after week 20.

Arm/Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be 18 to 65 years of age, inclusive.
• Be able to provide informed consent and ask relevant questions.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Be willing to adhere to the study medication regimen
• Meet DSM-5 criteria for moderate or severe methamphetamine, cocaine or prescription stimulant use disorder.
• Self-report methamphetamine, cocaine or prescription stimulant use on 18 or more days in the 30-day period prior to written informed consent using the Timeline Followback (TLFB).
• Have an initial body mass index (BMI) at screening of:
• kg/m2 or greater (obesity)
• kg/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).
• If biologically female and is or becomes sexually active with a biological male, must agree to use acceptable methods of contraception and have urine pregnancy testing during participation in the study, unless unable to get pregnant
• a. Appropriate birth control methods include: i. Oral contraceptives, contraceptive patch, hormonal vaginal contraceptive ring (with restrictions related to dose change given the medication interactions between tirzepatide and oral contraceptives).
• ii. Barrier (diaphragm or condom) iii. Contraceptive implant iv. Medroxyprogesterone acetate injection v. Intra-uterine device vi. Complete abstinence from sexual intercourse vii. Surgical sterilization
• Agreement to adhere to Lifestyle Considerations throughout study duration

You may not qualify if:

• Current or recent use (within 3 months prior to consent) of other tirzepatide-containing products or any other GLP-1 receptor agonist
• Current or recent use (within 30 days) of sulfonylureas, other concomitantly administered insulin secretagogue, or insulin
• Current or recent use (within 3 months prior to consent) of other weight loss agents
• Weight loss surgery within 12 months prior to consent
• Current eating disorder per clinician evaluation
• Personal or family history of Medullary Thyroid Carcinoma
• History of Multiple Endocrine Neoplasia syndrome type 2
• Known serious hypersensitivity (e.g., anaphylaxis, angioedema) to tirzepatide or any of the excipients in tirzepatide
• History of angioedema or anaphylaxis with a GLP-1 receptor agonist
• Current Stage 3 or higher Chronic Kidney Disease, defined as eGFR \<60 at Screening
• Current inadequately controlled diabetes, defined as HbA1c \> 7.0 at Screening
• History of diabetic retinopathy
• Current pregnancy or lactation
• Treatment with another investigational drug or intervention within the past one month (30 days prior to consent)
• Have any condition for which study participation would not be in their best interest (e.g., cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments, in the opinion of the investigator or their designee.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75247, United States

Location

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Manish Jha, M.B.B.S.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virgilio Garza, B.S.

CONTACT

(682) 376-8622; Virgilio.Garza@UTSouthwestern.edu

Teresa Slettebo, B.A.

CONTACT

(214) 998-5649; Teresa.Slettebo@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MBBS, Associate Professor

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 9, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)