Liver Adiposity Effects on Pediatric Statin

Effects of Pediatric Liver Adiposity on Statin Disposition and Response

Single center, open-label, prospective investigation to quantify the effects hepatocellular fat has on hepatic statin transport and response in children and adolescents in obese and non-obese children and adolescents 8-21 years of age with normal, wild-type SLCO1B1 c.521TT genotype that are dosed rosuvastatin

Study Overview

• Status: Recruiting
• Conditions: Cholesterol; Lipidosis
• Intervention / Treatment: Drug: Rosuvastatin 10mg

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jonathan Wagner, DO; Phone Number: 816-731-7240; Email: jbwagner@cmh.edu
• Study Contact Backup: Name: Jazzie K Holliday; Phone Number: 816-302-3500; Email: jkholliday@cmh.edu

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Hospital
      • Contact: Jonathan B Wagner, DO; Phone Number: 59373 816-234-3000; Email: jbwagner@cmh.edu
      • Principal Investigator: Jonathan B Wagner, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 8-21 years
• LDL cholesterol >130mg/dl (>95% percentile)
• SLCO1B1 c.521TT genotype
• Provide informed permission-assent(<18 yrs.) or consent (≥18 yrs.)
• Fasting overnight (~8 hrs.)
• Enrolled in Cardiology Pharmacogenomic Repository

Exclusion Criteria:

• Pregnancy
• Non-fasting
• Non-removable metal in body or MRI unsafe
• Currently on statin therapy and unwilling to wash out of statin therapy for at least 4 weeks prior to Visit 1 and throughout the duration of the study.
• Underlying unrepaired congenital or acquired cardiovascular defects or repaired congenital or acquired cardiovascular defects with hemodynamically significant residual disease.
• History of underlying or laboratory evidence of underlying intestinal, metabolic, autoimmune, renal disease that can alter rosuvastatin disposition* (absorption, metabolism, distribution, or clearance)
• Pharmacotherapy that interacts with statins (OATP1B1 inducers/inhibitors) *
• Inability to swallow a tablet
• >5x the age-specific upper limit of normal for AST, ALT, total and conjugated bilirubin
• Diarrhea in the last 24 hours
• Anything that would exclude a participant from completing an MRI, such as pacemakers, claustrophobia, or body habitus (e.g., weight greater than 350 lbs.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Baseline Mevalonate and MRI Imaging
Experimental: Mevalonate Change After Rosuvastatin	Drug: Rosuvastatin 10mg; Rosuvastatin will be administered to all participants on Study Day #2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate effect of Liver Fat Percentage (on MRI) on AUC	We expect that increased liver adiposity will be associated with higher systemic statin exposure and thus, place those with higher liver adiposity fraction at increased risk for drug toxicity.	2 years
Evaluate effect of Liver Fat Percentage (on MRI) on change on plasma mevalonate level	We expect that increased liver adiposity will be associated with an attenuated mevalonate response to a statin in obese children placing those with increased liver adiposity at risk for treatment failure.	2 years

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 22, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Lipidoses; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Rosuvastatin Calcium
• Other Study ID Numbers: STUDY00001550

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.: Yes