Liver Adiposity Effects on Pediatric Statin

Phase 1

Recruiting

• Conditions: Cholesterol; Lipidosis
• Interventions: Drug: Rosuvastatin 10mg

• Registration Number: NCT04903223
• Lead Sponsor: Children's Mercy Hospital Kansas City

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2021-05-17
• Study First Submitted QC: 2021-05-22
• Study First Posted: 2021-05-26
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-03
• Primary Completion: 2025-01-30
• Study Completion: 2025-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Read More

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.)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mevalonate Change After Rosuvastatin	Rosuvastatin 10mg	-

Primary Outcome Measures

Name	Time	Method
Evaluate effect of Liver Fat Percentage (on MRI) on AUC	2 years	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.
Evaluate effect of Liver Fat Percentage (on MRI) on change on plasma mevalonate level	2 years	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.

Trial Locations

Locations (1)

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States