ObesityPhase 2TRI-MRNCT07693608
An Open-Label Tirzepatide Trial for Comorbid Obesity and Stimulant Use Disorder
A Phase 2 study testing Tirzepatide in people with Obesity and Methamphetamine Use Disorder, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity, Methamphetamine Use Disorder, Cocaine Use Disorder
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2026to 1 Mar 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (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).
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- Have an initial body mass index (BMI) at screening of:
- 30 kg/m2 or greater (obesity)
- 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).
- 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
- 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).
- 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
Who cannot join
- Current or recent use (within 3 months prior to consent) of other tirzepatide-containing products or any other GLP-1 (Glucagon-Like Peptide-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
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- 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 (estimated Glomerular Filtration Rate) <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.
- Require immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.
- Any contraindications to MRI, including pacemakers or metallic objects in the body.
- Any claustrophobia or other conditions which may result in inability to lie still in the MRI scanner for 1 hour or more.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: An Open-Label Tirzepatide Trial for Comorbid Obesity and Stimulant Use Disorder Using fMRI to Identify Novel Neural Biomarkers
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.
Read the detailed description
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.
- Being tested
- Tirzepatide
- Keywords
- Methamphetamine, Cocaine, Stimulants, MUD, Overweight, Obesity, Tirzepatide, Weight management, MRI
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide Arm | 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. Receives: Drug: Tirzepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 32 weeks
Secondary outcomes (4)
Changes in body mass index from baseline to the end of the 20-week treatment phase
Body mass index will be calculated using measurements of height and weight.
Measured: 20 weeks
Feasibility of using tirzepatide in individuals with Stimulant 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.
Measured: 20 weeks
Changes in High-sensitivity C-reactive protein (hs-CRP) levels from baseline to the end of the 20-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.
Measured: 20 weeks
Changes in gastrointestinal symptom severity from baseline until the end of the 20-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.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2026
- Study start19 Aug 2026
- Primary completion1 Feb 2030 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Manish Jha, University of Texas Southwestern Medical Center
- Investigators
- Manish Jha, M.B.B.S., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07693608
- Sponsor's protocol ID
- STU20260206
- Acronym
- TRI-MR
- Status last verified
- Aug 2026
- First submitted
- 2 Jul 2026
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No individual participant data is planned to be shared with other researchers.