Liver Adiposity Effects on Pediatric Statin

Cholesterol; Lipidosis Clinical Trial

Official title:

Effects of Pediatric Liver Adiposity on Statin Disposition and Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04903223
• Other study ID #: STUDY00001550
• Status: Recruiting
• Phase: Phase 1
• Start date: April 1, 2021
• Est. completion date: January 30, 2025

Study information

• Verified date: May 2024
• Source: Children's Mercy Hospital Kansas City
• Contact: Jonathan Wagner, DO
• Phone: 816-731-7240
• Email: jbwagner[@]cmh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 30, 2025
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 21 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Cholesterol; Lipidosis

Intervention

Drug:
• Rosuvastatin 10mg
Rosuvastatin will be administered to all participants on Study Day #2

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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