Tirzepatide for Obesity and Meth Use Disorder

Tirzepatide for Individuals With Comorbid Obesity and Methamphetamine Use Disorder

This is an open-label pilot 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 in individuals with comorbid methamphetamine use disorder.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Methamphetamine Use Disorder
• Intervention / Treatment: Drug: Tirzepatide

Detailed Description

This study will enroll up to 45 individuals with moderate-to-severe methamphetamine use disorder who meet the FDA-approved weight-related indication for tirzepatide [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) 27 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)].

Enrolled participants will receive weekly treatment with tirzepatide for a 32-week period that will be followed by 4-week-long observational follow-up. Participants of this study will be seen for weekly visits where they will complete clinical and/or laboratory assessments.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Be 18 to 65 years of age, inclusive.
2. Be able to provide informed consent and ask relevant questions.
3. Stated willingness to comply with all study procedures and availability for the duration of the study.
4. Be willing to adhere to the study medication regimen
5. Meet DSM-5 criteria for moderate or severe methamphetamine use disorder.
6. Self-report methamphetamine use on 18 or more days in the 30-day period prior to written informed consent using the Timeline Followback (TLFB).

7. Have an initial body mass index (BMI) at screening of:

   1. 30 kg/m2 or greater (obesity)
   2. 27 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).

8. 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

9. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

Exclusion Criteria:

1. Current or recent use (within 3 months prior to consent) of other tirzepatide-containing products or any other GLP-1 receptor agonist
2. Current or recent use (within 30 days) of sulfonylureas, other concomitantly administered insulin secretagogue, or insulin
3. Current or recent use (within 3 months prior to consent) of other weight loss agents
4. Weight loss surgery within 12 months prior to consent
5. Current eating disorder per clinician evaluation
6. Personal or family history of Medullary Thyroid Carcinoma
7. History of Multiple Endocrine Neoplasia syndrome type 2
8. Known serious hypersensitivity (e.g., anaphylaxis, angioedema) to tirzepatide or any of the excipients in tirzepatide
9. History of angioedema or anaphylaxis with a GLP-1 receptor agonist
10. Current Stage 3 or higher Chronic Kidney Disease, defined as eGFR <60 at Screening
11. Current inadequately controlled diabetes, defined as HbA1c > 7.0 at Screening
12. History of diabetic retinopathy
13. Current pregnancy or lactation
14. Treatment with another investigational drug or intervention within the past one month (30 days prior to consent)
15. 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.
16. Require immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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 32-week period in accordance with FDA-prescribing label guidelines.

Drug: Tirzepatide; Eligible participants who are enrolled will receive once-weekly subcutaneous injections of tirzepatide for a 32-week period. Following the instructions of the FDA-approved prescribing label, participants or a licensed study clinician will administer the tirzepatide injection subcutaneously in either the abdomen, thigh, or upper arm once weekly for 32 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. The recommended maintenance dosages per prescribing label are 5mg/week, 10mg/week, or 15mg/week injected subcutaneously. Maximum dosage (up to 15mg/week) will be optimized for each individual. We will use commercially available tirzepatide, primarily dispensed as ZEPBOUND® for this study, but in the event of medication shortage or other pharmacy-related issue, MOUNJARO® may be dispensed as an alternative.; Other Names: ZEPBOUND; MOUNJARO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of tirzepatide on self-reported use of methamphetamine	Self-reported use of methamphetamine 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.	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of using tirzepatide in individuals with Methamphetamine Use Disorder	Feasibility will be defined as the number of participants who receive a dose of tirzepatide of at least a 5mg/week for at least four weeks.	4 weeks
Changes in body mass index from baseline to the end of the 32-week treatment phase	Body mass index will be calculated using measurements of height and weight.	32 weeks
Changes in self-reported symptoms of anhedonia from baseline to the end of the 32-week treatment phase	Anhedonia, the inability to experience pleasure, will be assessed by the Snaith-Hamilton Pleasure Scale (SHAPS). The SHAPS questionnaire contains 14 items related to experiencing pleasure over the last several days. Participants are asked to rate their level of agreement or disagreement with each prompt. The scale has a scoring range of 0-14 where a higher point value indicates a higher level of anhedonia.	32 weeks
Changes in gastrointestinal symptom severity from baseline until the end of the 32-week treatment phase	Gastrointestinal symptom severity will be assessed by the Gastrointestinal Symptom Rating Scale (GSRS): a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. The GSRS scale is graded on a seven-point Likert-type scale where a lower score (1) represents less symptom severity and highest score (7) represents greater symptom severity.	32 weeks
Changes in High-sensitivity C-reative protein (hs-CRP) levels from baseline to the end of the 32-week treatment phase	Clinical laboratory assessments for High-Sensitivity C-Reactive Protein (HsCRP) test will be performed to help determine eligibility at screening and monitor participant's overall health condition.	32 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Manish Jha, M.B.B.S., University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Franken IH, Rassin E, Muris P. The assessment of anhedonia in clinical and non-clinical populations: further validation of the Snaith-Hamilton Pleasure Scale (SHAPS). J Affect Disord. 2007 Apr;99(1-3):83-9. doi: 10.1016/j.jad.2006.08.020. Epub 2006 Sep 20.
• Sobell LC, Sobell MB, Leo GI, Cancilla A. Reliability of a timeline method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations. Br J Addict. 1988 Apr;83(4):393-402. doi: 10.1111/j.1360-0443.1988.tb00485.x. No abstract available.
• Kulich KR, Madisch A, Pacini F, Pique JM, Regula J, Van Rensburg CJ, Ujszaszy L, Carlsson J, Halling K, Wiklund IK. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008 Jan 31;6:12. doi: 10.1186/1477-7525-6-12.
• Coffin PO, Suen LW. Methamphetamine Toxicities and Clinical Management. NEJM Evid. 2023 Dec;2(12):EVIDra2300160. doi: 10.1056/EVIDra2300160. Epub 2023 Nov 28.
• Tan B, Pan XH, Chew HSJ, Goh RSJ, Lin C, Anand VV, Lee ECZ, Chan KE, Kong G, Ong CEY, Chung HC, Young DY, Chan MY, Khoo CM, Mehta A, Muthiah MD, Noureddin M, Ng CH, Chew NWS, Chin YH. Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Int J Obes (Lond). 2023 Aug;47(8):677-685. doi: 10.1038/s41366-023-01321-5. Epub 2023 May 31.
• Barry D, Clarke M, Petry NM. Obesity and its relationship to addictions: is overeating a form of addictive behavior? Am J Addict. 2009 Nov-Dec;18(6):439-51. doi: 10.3109/10550490903205579.
• Volkow ND, Xu R. GLP-1R agonist medications for addiction treatment. Addiction. 2025 Feb;120(2):198-200. doi: 10.1111/add.16626. Epub 2024 Jul 24. No abstract available.
• Lahteenvuo M, Tiihonen J, Solismaa A, Tanskanen A, Mittendorfer-Rutz E, Taipale H. Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry. 2025 Jan 1;82(1):94-98. doi: 10.1001/jamapsychiatry.2024.3599.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Methamphetamine; Weight management; MUD; Tirzepatide; Methamphetamine Use Disorder
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: STU-2024-1221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data is planned to be shared with other researchers.

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