Liver Adiposity Effects on Pediatric Statin

Study Overview
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Brief Summary
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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

Official Title
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Effects of Pediatric Liver Adiposity on Statin Disposition and Response

Conditions
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Cholesterol; Lipidosis

Intervention / Treatment
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* Drug: Rosuvastatin 10mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single center, open-label, prospective, investigation to quantify the effects hepatocellular fat has on hepatic statin transport (SA1) and response (SA2) in children and adolescents.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |