Cholesterol; Lipidosis
Conditions
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
Interventions
Rosuvastatin will be administered to all participants on Study Day #2
Sponsors
Children's Mercy Hospital Kansas City
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
8 Years to 21 Years
Healthy volunteers
Yes
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactJonathan Wagner, DO
Backup ContactJazzie K Holliday
Outcome results
None listed