A Pilot Study of Losartan in the Treatment of Pediatric NAFLD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease among children and is closely associated with obesity and the metabolic syndrome. NAFLD increases risk of mortality and natural history studies of adults show that NAFLD is an independent risk factor for cardiovascular disease. Pediatric NAFLD is particularly concerning from a public health standpoint, as it represents an early and possibly more aggressive form of the disease. Currently there is no effective treatment for pediatric NAFLD.
Losartan is an orally-administered angiotensin II receptor antagonist which is currently on the market to treat high blood pressure. The renin-angiotensin-aldosterone (RAA) system has been shown to be important in many disease states including renal disease, cardiovascular disease, and NAFLD. Angiotensin antagonists are a class of medications that has been proposed as a novel treatment of NAFLD in part because they would treat both the factors increasing cardiovascular (CVD) risks as well as potentially improve steatosis, fibrosis and hepatic inflammation.
This study is a randomized, double-blinded, placebo-controlled pilot study to evaluate whether 8 weeks of Losartan will decrease inflammatory markers among children ages 12-19 with a current diagnosis of NAFLD. Efficacy will be assessed by improvement in alanine aminotransferase (ALT) from baseline. Secondary endpoints will include aspartate aminotransferase (AST), cytokeratin 18 levels, and fasting triglyceride levels among others. Safety will be assessed by the recording of adverse events, clinical laboratory parameters, vital signs and physical examinations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 11 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body Mass Index (BMI) > 85th% for age and gender
- •History of definite or borderline nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy using NASH Clinical Research Network (CRN) criteria
- •At least 2 months of attempted lifestyle changes after liver biopsy
- •Current ALT ≥ 3 times normal (69 U/L for girls, 78 U/L for boys) at enrollment
- •Glomerular filtration rate (GRF) > 90
- •Weight ≥ 62.5 kg
排除标准
- •Other chronic illness requiring daily medication (except medications for mild mental illness, acid reflux, allergies, stable attention deficit hyperactivity disorder (ADHD), or asthma)
- •Supplement or anti-oxidant therapy within past 2 weeks
- •Renal insufficiency
- •Cirrhosis and liver synthetic dysfunction (International Normalized Ratio ≥ 1.5)
- •History of hypotension
- •Diabetes (or fasting glucose > 125 mg/dL)
- •Acute illness within past 2 weeks prior to enrollment (fever > 100.4ºF)
- •Pregnancy
研究组 & 干预措施
Losartan then Placebo
0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks then placebo pill for 8 weeks
干预措施: Losartan (Drug)
Sugar pill
placebo pill taken for 8 weeks then 0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks
干预措施: Losartan (Drug)
结局指标
主要结局
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
时间窗: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)
The principal objective of this blinded, placebo controlled, crossover pilot study is to evaluate whether 8 weeks of losartan in children with nonalcoholic steatohepatitis (NASH) will decrease inflammation as measured by ALT.
次要结局
- Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment)(Baseline (Week 0 and 14), End of treatment (Week 8 and 22))
- Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment)(Baseline (Week 0 and 14), End of Treatment (Week 8 and 22))
- Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)(Baseline (Week 0 and 14), End of treatment (Week 8 and 22))
- Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment(Baseline, Week 8, Week 14, Week 22)
- Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment)(Baseline (Week 0 and 14), End of Treatment (Week 8 and 22))
研究者
Miriam Vos, MD
Assistant Professor of Pediatrics
Emory University