Clinical and Neurobehavioral Changes With Weight Loss Drug Discontinuation and Reinitiation

NCT07387796 | Not Yet Recruiting

• 1 other identifier: IRB-26-3
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical study with research procedures is to learn how stopping and restarting tirzepatide (a medication that helps regulate blood sugar and appetite) affects brain activity, behavior, and health in adults ages 18-70 who are currently taking tirzepatide. Specifically, the study aims to examine how a short pause in tirzepatide affects hunger, mood, sleep, and daily functioning; how stopping and restarting tirzepatide alters brain chemistry and brain responses to food-related images; and how these changes relate to health measures such as quality of life and emotional well-being. There is no comparison group; instead, researchers will assess changes within each participant across three time points: while taking tirzepatide, after stopping it for 3-4 weeks, and after restarting it for 6-8 weeks. Participants will attend three in-person visits lasting approximately 3-4 hours each, during which they will complete interviews, questionnaires, and cognitive tasks; provide a urine sample (pregnancy screening for females); undergo a brain scan using magnetic resonance imaging (MRI) and MR spectroscopy (MRS); and receive a kit to provide a small stool sample. Participants will also complete two brief check-in phone calls between visits and the online BrainHealth Index between sessions, which includes surveys and cognitive tasks. All changes to tirzepatide use will occur under the supervision of a study physician to support participant safety and comfort, and the total study duration is approximately 13 weeks.

Conditions

Drug Discontinuation; Substance Use Disorders; Eating Behavior Changes; Tirzepatide

Keywords

Tirzepatide; Drug Discontinuation; Substance Use Disorders; Eating Behavior Changes

Outcome Measures

Primary Outcomes (1)

• Change From On-Treatment to Discontinuation and Re-Initiation in Food Cue-Evoked BOLD Response in Reward and Salience Brain Regions

  This outcome measures within-participant change in blood-oxygen-level-dependent (BOLD) signal during a food cue reactivity task, assessed using functional magnetic resonance imaging (fMRI). BOLD response will be quantified as the mean percent signal change in predefined reward- and salience-related regions of interest (including the ventral striatum and insula) during food image presentation relative to non-food control images. Higher BOLD values indicate greater neural responsivity to food cues.

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

Secondary Outcomes (21)

• Change From Baseline in Resting-State Functional Connectivity Within Salience and Executive Control Networks

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change From Baseline in Brain Neuromelanin Signal

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change From Baseline in Brain Glutamate Levels

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change From Baseline in State Food Craving Severity

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change From Baseline in Trait Food Craving Severity.

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

Other Outcomes (4)

• Change From Baseline in Gut-Derived Neurotransmitter Levels.

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change From Baseline in Gut Microbiome and Inflammatory Marker Profiles

  Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation

• Change in Multidimensional Brain Health as Measured by the BrainHealth Index

  Between baseline and discontinuation (about 2 weeks after baseline), and between discontinuation and re-initiation (about 4 weeks after start of reinitiation)

Study Arms (1)

Tirzepatide Discontinuation and Re-Initiation Arm

EXPERIMENTAL

Participants in this single-group arm will complete three study visits that occur while they are taking tirzepatide, during a 3-4 week pause from the medication, and after they restart tirzepatide for 6-8 weeks. All medication changes are supervised by a study physician. At each visit, participants will complete interviews, questionnaires, cognitive tasks, magnetic resonance imaging (MRI) brain scans, and provide stool samples. They will also complete two short check-in phone calls and an online BrainHealth Index assessment between visits.

Other: Discontinuation and Reinitiation of Tirzepatide

Interventions

Discontinuation and Reinitiation of Tirzepatide OTHER

Participants will temporarily pause their tirzepatide medication for 3-4 weeks and then restart it for 6-8 weeks under the supervision of a study physician. The medication change is done only for research purposes to study how stopping and restarting tirzepatide affects brain activity, appetite, mood, and other health measures. During this period, participants will complete MRI scans, behavioral assessments, questionnaires, and provide stool samples across three study visits.

Tirzepatide Discontinuation and Re-Initiation Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years.
• Currently on tirzepatide.
• Currently receiving care from University of Texas- Southwestern (UTSW) Weight Wellness Clinic.
• Cognitively capable of understanding and signing informed consent.
• Be proficient in English.

You may not qualify if:

• History of major neurological or psychiatric disorders, including substance use disorders that might confound brain imaging results (e.g., stroke, epilepsy, multiple sclerosis, schizophrenia, major depression requiring hospitalization).
• Diagnosis of Type 2 Diabetes.
• Use of medications affecting weight other than tirzepatide.
• Pregnancy or breastfeeding.
• MR contraindications:
• Heart pacemaker, heart valve replacement, or aortic clips
• Metal fragments in the eyes, skin, or elsewhere in the body
• Brain clips or pieces of metal used in aneurysm surgery or intercranial bypass
• Venous umbrella
• Pieces of metal in the body resulting from work as a sheet-metal worker or welder
• Clips placed in an internal organ
• Prosthetic devices, such as middle ear, eye, joint, or penile implants
• Joint replacement
• Hearing aid that cannot be removed
• Neurostimulator

Sponsors & Collaborators

• The University of Texas at Dallas: lead
• University of Texas Southwestern Medical Center: collaborator

Study Sites (1)

Center for BrainHealth

Dallas, Texas, 75235, United States

Location

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MeSH Terms

Conditions

Substance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Study Officials

• Francesca Filbey, Doctor of Philosophy

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel M Poelker-Wells, Master of Science

CONTACT

972-883-3375; sxp230129@utdallas.edu

Linnea L Stahl, Master of Science

CONTACT

972-883-3304; Linnea.Stahl@UTDallas.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 8, 2026
• First Posted: February 4, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)