Brain Plasticity and GLP-1 Receptor Agonist Treatment for Obesity

NCT07021937 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: Pending
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity/Therapy

Keywords

adolescent; adult; brain function; glucagon-like peptide-1 receptor agonists; eating behaviors; appetite sensations

Outcome Measures

Primary Outcomes (4)

• hypothalamic functional activation

  blood oxygen-level dependent signal via resting-state functional magnetic resonance imaging

  From enrollment to the end of trial at 32 weeks

• hypothalamic functional connectivity

  blood oxygen-level dependent signal via resting-state functional magnetic resonance imaging

  From enrollment to the end of trial at 32 weeks

• ad libitum food intake

  Measured as kcal consumed from standardized ad libitum meal

  From enrollment to the end of trial at 32 weeks

• appetite sensations

  pre- and post-meal hunger, desire to eat, amount feel can eat, and fullness

  From enrollment to the end of trial at 32 weeks

Study Arms (6)

Pubertal Adolescent - Continuous Treatment

EXPERIMENTAL

Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 32 weeks of semaglutide (s.c.)

Drug: Semaglutide 1.7mg subcutaneous

Pubertal Adolescent - Early Treatment Cessation

EXPERIMENTAL

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

Drug: Semaglutide 1.7mg subcutaneous; Drug: Placebo

Post-Pubertal Adolescent - Continuous Treatment

EXPERIMENTAL

Post-pubertal adolescents defined as Tanner stage 5 and/or 16-18 y/o who will receive 32 weeks of semaglutide (s.c.)

Drug: Semaglutide 1.7mg subcutaneous

Post-Pubertal Adolescent - Early Treatment Cessation

EXPERIMENTAL

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

Drug: Semaglutide 1.7mg subcutaneous; Drug: Placebo

Adult - Continuous Treatment

ACTIVE COMPARATOR

Adults defined as 30-45 y/o who will receive 32 weeks of semaglutide (s.c.)

Drug: Semaglutide 1.7mg subcutaneous

Adult - Early Treatment Cessation

ACTIVE COMPARATOR

Adults defined as 30-45 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo

Drug: Semaglutide 1.7mg subcutaneous; Drug: Placebo

Interventions

Semaglutide 1.7mg subcutaneous DRUG

Semaglutide subcutaneous max dose of 1.7mg over 24 or 32 weeks of active treatment

Also known as: SEMA

Adult - Continuous Treatment; Adult - Early Treatment Cessation; Post-Pubertal Adolescent - Continuous Treatment; Post-Pubertal Adolescent - Early Treatment Cessation; Pubertal Adolescent - Continuous Treatment; Pubertal Adolescent - Early Treatment Cessation

Placebo DRUG

Placebo saline solution subcutaneous

Adult - Early Treatment Cessation; Post-Pubertal Adolescent - Early Treatment Cessation; Pubertal Adolescent - Early Treatment Cessation

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Minnesota: collaborator
• The Metis Foundation: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Obesity; Feeding Behavior

Interventions

semaglutide; Injections, Subcutaneous

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior, Animal; Behavior

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Allison Shapiro, PhD, MPH

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Allison Shapiro, PhD, MPH

CONTACT

3037241150; allison.shapiro@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: study statistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: June 15, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 30, 2031
• Study Completion (Estimated): April 30, 2031
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)