Brain Plasticity and GLP-1 Receptor Agonist Treatment for Obesity

Phase 3

Not yet recruiting

• Conditions: Obesity/Therapy
• Interventions: Drug: Semaglutide 1.7mg subcutaneous; Drug: Placebo

• Registration Number: NCT07021937
• Lead Sponsor: University of Colorado, Denver

Brief Summary

Glucagon-like peptide 1 receptor agonists (GLP-1RA), such as Ozempic and Wegovy, have been rapidly adopted for the treatment of obesity in both youth and adults. However, despite this rapid adoption and the known GLP-1RA mechanism of action for weight loss, which targets brain circuits responsible for appetite and eating behaviors, almost nothing is known about how these drugs affect the brain in youth who are treated for obesity, or how these drugs affect the brain of youth differently from adults. The goal of the current study is to compare youth and adults with obesity who are treated a GLP-1RA and measure potential difference in GLP-1RA associated change in brain function, appetite, and eating behaviors.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-03
• Study First Submitted QC: 2025-06-06
• Last Update Submitted: 2025-06-06
• Study First Posted: 2025-06-15
• Last Update Posted: 2025-06-15
• Study Start: 2026-05-01
• Primary Completion: 2031-04-30
• Study Completion: 2031-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• English-speaking
• male or female (sex assigned at birth)
• 12-18 y/o with obesity (BMI>120% of the 95th %ile)
• 30-45 y/o with obesity (BMI>35 kg/m2)

Exclusion Criteria

• treated with glucagon-like peptide-1 (GLP-1) agonists (e.g., exenatide, liraglutide, semaglutide, tirzepatide) for weight management in the prior 3 months
• currently taking anti-psychotic medications (anti-depressants accepted)
• diagnosis of type 2 diabetes
• current or lifetime anorexia nervosa or current bulimia nervosa
• head injury resulting in loss of consciousness >30min
• neurological disorder (e.g., Parkinson's disease) or history of stroke
• any contraindication to receiving a MRI (e.g., orthodontal braces)
• psychological/behavioral dysfunction (e.g., autism spectrum disorder) or physical impairment that would interfere with study procedures, as determined by study physician
• if female, desiring to become pregnant, or currently pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pubertal Adolescent - Continuous Treatment	Semaglutide 1.7mg subcutaneous	Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 32 weeks of semaglutide (s.c.)
Pubertal Adolescent - Early Treatment Cessation	Semaglutide 1.7mg subcutaneous	Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo
Pubertal Adolescent - Early Treatment Cessation	Placebo	Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo
Post-Pubertal Adolescent - Continuous Treatment	Semaglutide 1.7mg subcutaneous	Post-pubertal adolescents defined as Tanner stage 5 and/or 16-18 y/o who will receive 32 weeks of semaglutide (s.c.)
Post-Pubertal Adolescent - Early Treatment Cessation	Semaglutide 1.7mg subcutaneous	Post-pubertal adolescents defined as Tanner stage 5 and/or 16-18 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo
Adult - Early Treatment Cessation	Semaglutide 1.7mg subcutaneous	Adults defined as 30-45 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo
Post-Pubertal Adolescent - Early Treatment Cessation	Placebo	Post-pubertal adolescents defined as Tanner stage 5 and/or 16-18 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo
Adult - Continuous Treatment	Semaglutide 1.7mg subcutaneous	Adults defined as 30-45 y/o who will receive 32 weeks of semaglutide (s.c.)
Adult - Early Treatment Cessation	Placebo	Adults defined as 30-45 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo

Primary Outcome Measures

Name	Time	Method
hypothalamic functional activation	From enrollment to the end of trial at 32 weeks	blood oxygen-level dependent signal via resting-state functional magnetic resonance imaging
hypothalamic functional connectivity	From enrollment to the end of trial at 32 weeks	blood oxygen-level dependent signal via resting-state functional magnetic resonance imaging
ad libitum food intake	From enrollment to the end of trial at 32 weeks	Measured as kcal consumed from standardized ad libitum meal
appetite sensations	From enrollment to the end of trial at 32 weeks	pre- and post-meal hunger, desire to eat, amount feel can eat, and fullness

Trial Locations

Locations (1)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States