Clinical and Neurobehavioral Changes With Weight Loss Drug Discontinuation and Reinitiation

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

Interventions

OTHER

Discontinuation and Reinitiation of Tirzepatide

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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center

  collaborator OTHER

• The University of Texas at Dallas

  lead OTHER

Principal Investigators

• Francesca Filbey, Doctor of Philosophy · The University of Texas at Dallas

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2028-02-29

Completion

2029-02-28

Countries

• United States

Study Locations