Clinical and Neurobehavioral Changes With Weight Loss Drug Discontinuation and Reinitiation

Official title

Clinical and Neurobehavioral Changes With GLP-1 (Glucagon-like Peptide-1) Discontinuation

Overview

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.

Detailed description

This study specifically recruits individuals currently being prescribed for tirzepatide. The experimental design will consist of a brief discontinuation of the drug for roughly 3-4 weeks followed by a reinitiation of the medication. Prescription and administration of tirzepatide is done as part of normal patient care and is not a component of the study.

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.

Primary outcome measures

• Change From On-Treatment to Discontinuation and Re-Initiation in Food Cue-Evoked BOLD Response in Reward and Salience Brain Regions [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]

Secondary outcome measures (12)

• Change From Baseline in Resting-State Functional Connectivity Within Salience and Executive Control Networks [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Brain Glutamate Levels [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in State Food Craving Severity [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Blood-Brain Permeability Levels [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Trait Food Craving Severity. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Addictive-Like Eating Symptoms. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Intrusive Food-Related Thoughts. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Dietary Pattern Quality. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Perceived Loss of Control Over Eating. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Psychological Responsiveness to Food Availability. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Uncontrolled Eating Behavior. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]
• Change From Baseline in Mood Disturbance. [Time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Current diagnosis of an eating disorder.
• 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
• Insulin pump
• Shunts or stents
• Metal mesh or coil implants
• Metal plate, pin, screws, or wires, or any other metal implants

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Center for BrainHealth — Dallas

Publications

• Lin Z, Jiang D, Liu D, Li Y, Uh J, Hou X, Pillai JJ, Qin Q, Ge Y, Lu H. Noncontrast assessment of blood-brain barrier permeability to water: Shorter acquisition, test-retest reproducibility, and comparison with contrast-based method. Magn Reson Med. 2021 Jul;86(1):143-156. doi: 10.1002/mrm.28687. Epub 2021 Feb 8. PMID 33559214
• Skevington SM, Lotfy M, O'Connell KA; WHOQOL Group. The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res. 2004 Mar;13(2):299-310. doi: 10.1023/B:QURE.0000018486.91360.00. PMID 15085902
• Schulte EM, Gearhardt AN. Development of the Modified Yale Food Addiction Scale Version 2.0. Eur Eat Disord Rev. 2017 Jul;25(4):302-308. doi: 10.1002/erv.2515. Epub 2017 Mar 29. PMID 28370722
• Racine SE, Horvath SA, Brassard SL, Benning SD. Effort expenditure for rewards task modified for food: A novel behavioral measure of willingness to work for food. Int J Eat Disord. 2018 Dec 31. doi: 10.1002/eat.22999. Online ahead of print. PMID 30597585
• Lowe MR, Butryn ML, Didie ER, Annunziato RA, Thomas JG, Crerand CE, Ochner CN, Coletta MC, Bellace D, Wallaert M, Halford J. The Power of Food Scale. A new measure of the psychological influence of the food environment. Appetite. 2009 Aug;53(1):114-8. doi: 10.1016/j.appet.2009.05.016. Epub 2009 Jun 12. PMID 19500623
• Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB. PMID 12900694
• Karlsson J, Persson LO, Sjostrom L, Sullivan M. Psychometric properties and factor structure of the Three-Factor Eating Questionnaire (TFEQ) in obese men and women. Results from the Swedish Obese Subjects (SOS) study. Int J Obes Relat Metab Disord. 2000 Dec;24(12):1715-25. doi: 10.1038/sj.ijo.0801442. PMID 11126230
• Baker F, Denniston M, Zabora J, Polland A, Dudley WN. A POMS short form for cancer patients: psychometric and structural evaluation. Psychooncology. 2002 Jul-Aug;11(4):273-81. doi: 10.1002/pon.564. PMID 12203741

Identifiers

NCT: NCT07387796 · IRB-26-3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗