Effects of Pediatric Liver Adiposity on Statin Disposition and Response
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Evaluate effect of Liver Fat Percentage (on MRI) on AUC
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.)
研究组 & 干预措施
Mevalonate Change After Rosuvastatin
干预措施: Rosuvastatin 10mg (Drug)
结局指标
主要结局
Evaluate effect of Liver Fat Percentage (on MRI) on AUC
时间窗: 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
时间窗: 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.
次要结局
未报告次要终点
研究者
Jon Wagner
Principal Investigator
Children's Mercy Hospital Kansas City