Bone Metabolism in 12-21 Year Olds Undergoing Glucagon Like Peptide (GLP)-1 Receptor Agonist Therapy

NCT06903923 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HSR302394R01HD118635
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare bone health markers over 24 months in participants 12 - 21 years of age with obesity who are starting the glucagon-like peptide-1 receptor agonists (GLP-1RAs) as compared to those with similar weight followed by lifestyle management. Participants will:

• Take GLP-1RA as prescribed or continue to work on lifestyle management for weight loss
• Take provided calcium and vitamin D supplements
• Attend 6 study visits over 24 months with two at the beginning and then every 6 months that include:
• History and Physical Exams
• Lab Work
• Imaging studies
• Questionnaires
• 24-hour dietary recalls

Conditions

Obesity in Children; Bone Strength; GLP - 1; Lifestyle Modification; Bone Density; Obesity

Keywords

obesity; obesity in children; bone strength; GLP-1; Lifestyle modification; bone density; semaglutide; liraglutide

Outcome Measures

Primary Outcomes (1)

• 24-month change in total vBMD at the distal radius

  Using repeated measures analysis, the investigators will compare change in radius vBMD after 24 months of treatment with GLP-1 RAs vs. routine care

  24 months

Secondary Outcomes (7)

• 24-month change in total vBMD at the distal tibia

  24 months

• 24-month change in radial and tibial trabecular vBMD

  24 months

• 24-month change in total hip and spine areal BMD

  24 months

• 24-month change in strength estimates (failure load) at the radius and tibia

  24 months

• 24-month change in load-to-strength ratio at the wrist and hip

  24 months

Study Arms (2)

GLP-1 Receptor Agonist

ACTIVE COMPARATOR

Drug: GLP-1 receptor agonist

Lifestyle Intervention

PLACEBO COMPARATOR

Behavioral: Lifestyle intervention

Interventions

GLP-1 receptor agonist DRUG

Participants prescribed a GLP-1 receptor agonist by their physician will be enrolled in this arm of the study. All participants will receive study provided calcium \& vitamin D supplement to support bone health and to reduce this as a confounding factor in overall outcomes

GLP-1 Receptor Agonist

Lifestyle intervention BEHAVIORAL

Participants receiving usual lifestyle interventions will be enrolled in this arm of the study. All participants will receive study provided calcium \& vitamin D supplement to support bone health and t

Lifestyle Intervention

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adolescents and young adults with obesity 12-21 years old starting GLP-1 RA therapy (except for dulaglutide or exenatide) or followed with 'usual' care.
• Diagnosis of obesity (BMI ≥ 95th percentile for age and sex). The FDA has approved the use of GLP-1 RAs (liraglutide and semaglutide) for adolescents ≥ 12 years old with BMI ≥ 95th percentile for age and sex, and tirzepatide for adults with obesity. Those in the GLP-1 RA arm must have demonstrated efforts at weight loss with 'usual' care, and consistent compliance with appointments and recommendations.
• Participants must demonstrate sufficient maturity, psychological stability and cognitive capacity to recognize the significance of being on medical therapy and implement required behavioral changes
• Patients taking orlistat as a precursor to GLP-1 RA therapy due to insurance requirements may be included given minimal effects on weight.
• Use of the following contraceptive methods is permitted: Combine oral contraceptives (COCs); continuous oral progestin; Progestin-releasing intrauterine device (IUD); Progestin implant; transdermal patch.
• Patients with celiac disease will be included if the condition is well controlled and they are on a gluten free diet with normal 25(OH)D levels confirmed by clinical labs within 3 months of enrollment in the study. If a patient does not have recent 25(OH)D results, we will add this to the screening labs.

You may not qualify if:

• Current or previous history of pregnancy and breast feeding.
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 if in the GLP-1 RA group.
• \> 5 kg weight loss over 3 months given the known impact of significant weight loss on bone density.
• Use of dulaglutide and exenatide (of the GLP-1 RAs) given minimal weight loss with these drugs.
• Use of medications such as metformin, phentermine, or topiramate that may cause weight loss, or obesogenic antipsychotic medications if treated for \<3 months, or if dosage is not stable for \>2 months.
• Medications other than calcium or vitamin D that affect bone, such as systemic glucocorticoids, phenytoin, phenobarbitone (unless there is a washout period of 3 months prior to enrollment if discontinuation is medically permissible)
• Female participants on hormonal contraception will be excluded if this involves use of depot medroxyprogesterone acetate (DMPA). DMPA has profound deleterious effect on bone density, which could confound study outcomes related to bone health. Rationale: DMPA has a well-documented deleterious effect on bone density, which could confound study outcomes related to bone health or metabolic parameters.
• Medical conditions known to impact weight or bone density, such as chronic gastrointestinal disorders (including inflammatory bowel disease), other inflammatory conditions, such as rheumatoid arthritis or ankylosing spondylitis, untreated thyroid disease, and hypercortisolemia.
• HbA1C \>8% (to avoid deleterious effects on bone from uncontrolled T2DM).
• Smoking \>10 cigarettes/day given deleterious effects on bone; substance abuse per DSM-5.
• Weight \>450 lbs due to limits for DXA scanners.
• History of metabolic and bariatric surgery.
• Judged by the investigators to be inappropriate for the study for other reasons not detailed above.

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Pediatric Obesity; Obesity

Condition Hierarchy (Ancestors)

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

Study Officials

• Madhusmita Misra, MD, MPH

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madhusmita Misra, MD, MPH

CONTACT

434-924-9141; madhusmita.misra@uvahealth.org

Christine Burt Solorzano, MD

CONTACT

434-924-9084; christine.burtsolorzano@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Participants prescribed GLP-1 receptor agonists or lifestyle intervention by their treating physician will be followed over 24 months
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Both groups (GLP-1 and lifestyle management) will be provided with the same nutritional supplements of calcium and vitamin D while they start and continue their prescribed/guided weight loss interventions.

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF
• Time Frame: Data sharing will occur no later than the end of performance period of the extramural award that generated the data. There is no end date planned at this time.
• Access Criteria: Study investigators will make access to deidentified data available via repository without restriction to access. Data available will include deidentified demographic data and those related to primary and secondary endpoints.

Locations

US (1)