A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.
A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.
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DOI：
10.1186/s40814-018-0306-4
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发表时间：
2018-01-01
影响因子：
1.7
通讯作者：
Welsh, Jean
中科院分区：
文献类型：
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作者：
Vos, Miriam B;Jin, Ran;Welsh, Jean
背景：非酒精性脂肪性肝病（NAFLD）是儿童最常见的肝病，目前尚无FDA批准的治疗方法。纤溶酶原激活物抑制剂-1（派-1）在NAFLD儿童中升高，并与疾病严重程度增加相关。氯沙坦钾（氯沙坦）是一种血管紧张素II受体阻滞剂（ARB），可减少派-1的产生并改善胰岛素敏感性，已被提议作为儿童NAFLD的治疗方法，但以前尚未进行过测试。这是一项为期8周的随机、双盲、安慰剂对照、2a期，交叉研究在12名血压正常、经活检证实患有非酒精性脂肪性肝炎（NASH）的儿童中，每天口服50 mg氯沙坦的安全性和初步疗效（条件之间有6周的洗脱期）。12名儿童参加了研究，9名儿童完成了所有访视。研究期间未发生血压变化或严重不良事件。与安慰剂时间段相比，氯沙坦治疗组观察到丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和稳态模型评估胰岛素抵抗（HOMA-IR）的改善趋势。与安慰剂组相比，氯沙坦组有更多的受试者ALT下降（89% [89] vs. 56% [5/9]）。结论：该数据提供了初步证据，表明氯沙坦治疗NAFLD儿童8周以上是安全的，并支持考虑进行更大规模的研究来测试其疗效。试验注册：URL和试验识别号：https：//clinicaltrials.gov/show/NCT01913470，NCT 01913470。注册日期：2013年8月1日。
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously been tested.METHODS: This was an 8-week randomized, double-blind, placebo-controlled, phase 2a, crossover study (with a 6-week washout between conditions) for safety and preliminary efficacy of losartan 50mg a day taken orally in 12 normotensive children with biopsy proven nonalcoholic steatohepatitis (NASH).RESULTS: Twelve children enrolled in the study, and nine completed all visits. No changes in blood pressure or serious adverse events occurred during the study. Trends in improvement in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and homeostatic model assessment insulin resistance (HOMA-IR) were seen with losartan treatment compared to the placebo time-period. More participants decreased ALT on losartan as compared to placebo (89% [8 out 9] vs. 56% [5 out of 9], respectively).CONCLUSIONS: This data provides preliminary evidence that losartan treatment is safe over 8weeks in children with NAFLD and supports consideration of larger studies to test its efficacy.TRIAL REGISTRATION: URL and trial identification number: https://clinicaltrials.gov/show/NCT01913470, NCT01913470.Date registered: August 1, 2013.