Mitigation of Cardiovascular Disease Risks in Children With Extreme Obesity (MODERN)

Mitigation of Cardiovascular Disease Risks in Children With Extreme Obesity (MODERN)

The goal of this clinical trial is to learn if the drug semaglutide changes markers of disease risk as it relates to weight in children ages 12-15 years old who are obese (class 2 or 3). The main questions it aims to answer are:

• How do the rate of weight loss, body mass index (BMI), body composition, heart structure and function, and exercise ability interact with one another in the study population at enrollment?
• How do risk markers of disease change over the study in the study participants who are given semaglutides to help with weight loss?
• Are there differences in the above factors between males and females and are there key factors to help improve the outcomes?

Participants will be given semaglutide for this study. During the course of the study, participants will:

• have two cardiac MRI scans OR two cardiac echocardiograms (one before starting semaglutide and one around 12 months after taking the drug)
• have body composition and fitness levels assessed twice (before semaglutide and around 12 months after taking it) and have urine specific gravity (USG) measured
• have extra blood drawn when labs their doctor orders are already being drawn (once at the beginning of the study, once around 6 months after enrollment, and once at the end of the study)
• have follow up visits with the study doctor
• be asked to take a pregnancy test if they are female and have started menstruation

Study Overview

• Status: Recruiting
• Conditions: Weight Loss; Weight Management; Obesity and Overweight; Obese Adolescents; Cardiovascular Disease Risk Factor
• Intervention / Treatment: Drug: Ozempic®

Detailed Description

This is an observational study in which all participants will be given semaglutide. There will be no randomization and no placebo.

Participants will be in the study for 12 months (+/- 2 months) depending on when they reach the maintenance dose of semaglutide.

Blood and urine will be maintained by the principal investigator indefinitely. Identifiers will be removed from the samples.

Approximately 50 patients will be enrolled.

The study drug, Ozempic, is FDA approved.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Margaret Murphy, RD PhD; Phone Number: 859-323-2969; Email: maggie.murphy@uky.edu
• Study Contact Backup: Name: Heather Collins, BSN RN CCRP; Phone Number: 859-562-1103; Email: heather.collins1@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University of Kentucky
      • Sub-Investigator: Robin Shoemaker, PhD
      • Contact: Amanda Wilburn, BA CCRP; Phone Number: 8595620670; Email: amanda.wilburn@uky.edu
      • Contact: Nermin Ahmed, RD PhD; Email: nermin.s@uky.edu
      • Principal Investigator: John Bauer, PhD
      • Sub-Investigator: Jody Clasey, PhD
      • Sub-Investigator: Hong Huang, PhD
      • Sub-Investigator: Margaret Murphy, RD PhD
      • Sub-Investigator: Aurelia Radulescu, MD
      • Sub-Investigator: Preeti Ramachandran, MD
      • Sub-Investigator: Douglas Schneider, MD
      • Sub-Investigator: Aftab Chishti, MD
      • Sub-Investigator: Stefan Kiessling, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the University of Kentucky's High BMI and/or Pediatric Nephrology Clinics.

Description

Inclusion Criteria:

• Patient seen at University of Kentucky Pediatric High BMI Clinic
• Diagnosis of Obesity Class 2 or 3
• Meeting the clinical criteria for the medical intervention with semaglutide for weight loss

Exclusion Criteria:

• Any current prescribed anti-obesity medications (AOM) such as Orlistat, Phentermine, Qsymia (Phentermine/Topiramate), Liraglutide, Semaglutide, and Setmelanotide
• Any current prescribed anti-hypertensive medications
• Any specific end-organ acute concerns (kidney disease, liver disease, congenital disease).
• Any active infections at enrollment.
• Any systemic steroid use longer than 3 month use or within the last month before enrollment (not including inhaled, ophthalmic, intranasal, and topical).
• Any limitations that would make exercise testing not possible.
• Any congenital abnormality or genetic syndrome known to be associated with obesity
• Pregnancy
• Inability to receive an MRI
• Personal or family history of medullary thyroid carcinoma (per product insert)
• Patients with Multiple Endocrine Neoplasia syndrome type 2 (per product insert)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment Group; All participants in this study will be given the study drug.	Drug: Ozempic®; The study medication will be given in accordance with standard of care dosing schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in medication use	This will be assessed by reviewing changes in the electronic medical record	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Lipid Profile	plasma/serum samples will be analyzed. blood lipid panel to include total cholesterol (mg/dL), HDL (mg/dL), triglycerides (mg/dL), and LDL (mg/dL) will be assessed	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in C-reactive protein	data obtained from blood samples	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Tumor necrosis factor	data obtained from blood samples	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Interleukin-6	data obtained from blood samples	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Adiponectin	data obtained from blood samples	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Soluble Intercellular Adhesion Marker	data obtained from blood samples	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Changes in Renin-Angiontensin-Alsosterone System biomarkers profiling	Changes in RAAS biomarkers at the defined study points will be evaluated.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Systolic Blood pressure		Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Diastolic Blood pressure	Blood pressure (systolic/diastolic) (mmHg) ambulatory blood pressure monitoring (ABPM) (mmHg) will be taken at the listed timepoints.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in ambulatory blood pressure		Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac structure	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed including overall heart and chamber size, wall thickness, etc.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac function (Ejection Fraction)	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac function (Stroke Volume (SV)	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac function (Cardiac Output (CO)	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac function (Wall motion)	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Cardiac function (Valve motion)	Changes from baseline cardiac MRI and/or cardiac echocardiograms (ECHO) will be assessed.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Dietary habits	It assesses the frequency and quality of dietary habits, such as the consumption of fruits, vegetables, whole grains, and unhealthy foods like sugary snacks and fast food. The scoring is typically based on a scale representing frequency: 0 = Never or less than once per week, 1 = 1-2 times per week, 2 = 3-4 times per week, 3 = 5-6 times per week, 4 = Daily or more. Higher scores on the healthy scale = better dietary habits	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in exercise habits	Assessed with the BMI Clinic dietary and exercise habit survey in which participants record the frequency of activities. It assesses the frequency, duration, and/or intensity of physical activity (e.g., walking, moderate activity, vigorous activity, including aerobic and strength training). For interpretation: High Score: Indicates sufficient physical activity Low Score: Suggests insufficient physical activity	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Patient Health Questionnaire-9 (PHQ-9)	The PHQ-9 is a 9-item self-report questionnaire that is widely used to assess depression symptom severity. A PHQ-9 score ≥10 has a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Higher scores indicating greater depression severity.	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Generalized Anxiety Disorder-7 questionnaire (GAD-7)	A 7 item self-complete questionnaire with very good sensitivity (89%) and specificity (82%) for Generalised Anxiety Disorder (GAD). Response scores for each item ranging from 0 (not at all) to 3 (every day). The range for the total score is 0 to 21, with higher scores representing greater symptoms of anxiety	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Anthropomorphic outcomes - Body Mass Index (BMI)		Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Anthropomorphic outcomes - Waist circumference		Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Anthropomorphic outcomes - Bioimpedence	Whole-body electrical resistance will be measured with the subjects using the BodyStat Quadscan 4000 Bioelectric Impedance Analyzer	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Anthropomorphic outcomes - Resting metabolic rate	A handheld resting metabolic rate (RMR) calculator/indirect calorimeter (MedGem RMR) will be used to estimate the RMR (caloric needs).	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Anthropomorphic outcomes - Cardiorespiratory Fitness	Maximal Graded Exercise Testing (Maximal GXT): The maximal graded exercise tests will be performed using an indirect calorimetry testing system	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in complete blood count (CBC)	plasma/serum samples will be analyzed	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Liver panel profile	-plasma/serum samples will be analyzed. The individual components are grouped as a panel to for an overall evaluation of the system's functioning	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Renal panel profile	-plasma/serum samples will be analyzed. The individual components are grouped as a panel to for an overall evaluation of the system's functioning	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Thyroid panel profile	-plasma/serum samples will be analyzed. The individual components are grouped as a panel to for an overall evaluation of the system's functioning	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Fasting glucose	-plasma/serum samples will be analyzed	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in Fasting Insulin	-plasma/serum samples will be analyzed	Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment
Change in hyperglycemia assessed by Homeostatic Model Assessment of Insulin Resistance, (HOMA-IR)		Enrollment, 6 months post enrollment, 12 months +/- 2 months post enrollment

Collaborators and Investigators

• Sponsor: John Bauer
• Investigators: Study Chair: John Bauer, PhD, University of Kentucky; Principal Investigator: Margaret Murphy, RD PhD, University of Kentucky; Study Director: Aurelia Radulescu, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: May 2, 2025
• First Posted (Actual): May 13, 2025

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: obesity; overweight; adolescent; semaglutide; weight loss; weight management; Ozempic; Wegovy
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight Changes; Overweight; Obesity; Weight Loss; Cardiovascular Diseases; Body Weight; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: 98420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No