Amino Acids and Pediatric Hepatic Steatosis

氨基酸和小儿脂肪肝

• 批准号: 10747273
• 负责人: ROBERT R WOLFE
• 金额: $ 88.3万
• 依托单位: AMINO COMPANY LLC, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10747273
• 关键词: 17 year old; 18 year old; Adherence; Adolescent; Adolescent obesity; Adverse event; Age; Aging; Alanine Transaminase; Amino Acids; Base Composition; Behavior Therapy; Benefits and Risks; Biopsy; Blinded; Body Composition; Body Weight decreased; Caloric Restriction; Cardiovascular Diseases; Child; Childhood; Chronic; Cirrhosis; Clinical Trials; Consumption; Creatinine; Cross-Over Studies; Documentation; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Essential Amino Acids; Exercise; Experimental Designs; Fatty Liver; Fatty acid glycerol esters; Female; Female Adolescents; Food; Formulation; Glutathione; Individual; Inflammation; Intervention; Liver; Liver diseases; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Marketing; Measures; Medical; Medical Societies; Metabolic; New Drug Approvals; Non-Insulin-Dependent Diabetes Mellitus; North America; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Plasma; Polycystic Ovary Syndrome; Positioning Attribute; Premature Mortality; Protocols documentation; Protons; Puberty; Public Health; Publishing; Recommendation; Safety; Subgroup; Triglycerides; Vitamin E; Youth; alcohol use disorder; cardiovascular health; clinical diagnosis; density; dietary supplements; dosage; emerging adult; exercise program; improved; inclusion criteria; insulin sensitivity; liver stiffness; male; non-alcoholic; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; nutrition; obesity in children; primary endpoint; randomized, clinical trials; secondary endpoint; sex; success; treatment effect; treatment guidelines; very low density lipoprotein triglyceride; weight loss program

7. Project Summary/Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in North America (1). Hepatic steatosis (HS) is the hallmark of NAFLD (2). NAFLD may transition in sub-groups to chronic inflammation (non- alcoholic steatohepatitis, NASH), and ultimately to cirrhosis. HS is prevalent in all stages of NAFLD. 3-10% of all children in the US and 40-70% of obese children have HS (3). There are approximately 15 million obese children in the US (4), meaning that as many as 10 million youths have HS. Pediatric HS is associated with premature mortality due to type 2 diabetes (T2D), cardiovascular disease (CVD) and progressive liver disease in early adulthood (5,6). Successful treatment of pediatric HS is therefore central to long-term metabolic and cardiovascular health. Recommended options are largely limited to behavioral modifications (i.e., weight loss and exercise) and nutritional supplement with Vitamin E (3,5-7). There is no FDA-approved drug for the treatment of NAFLD in individuals of any age. We propose to perform a randomized clinical trial (RCT) in youths with HS. We will expand our previous study in which treatment with our essential amino acid (EAA)-based composition called AMS2392 reduced liver fat in adolescent females with polycystic ovary syndrome (PCOS). Specific Aim 1. We will investigate the hypothesis that 8 weeks of treatment with AMS2392 will reduce liver fat in youths with HS. We will perform a double-blind RCT in 48 male and female youths 13 to 18 years of age (Tanner stage 4 or 5) with biopsy-documented HS. Liver fat content will be measured by magnetic resonance imaging (MRI) at the outset and after the eight-week intervention. Specific Aim 2. We propose that secondary end points of liver stiffness, body composition, insulin sensitivity, and plasma concentrations of very-low density triglycerides (VLDL-TG), alanine transaminase (ALT), ApoB100, creatinine and insulin sensitivity will be improved in the group receiving AMS2392 as compared to placebo. Specific Aim 3. Adherence to protocol will be greater than 90% and there will be no adverse events in those consuming AMS2392, including no change in plasma glutathione concentration. Completion of this RCT will provide information regarding efficacy, effect size, safety and tolerance that will position us to successfully market AMS2392 as a medical nutrition product.

7.项目总结/摘要 非酒精性脂肪肝（NAFLD）是北美最常见的肝病（1）。肝 脂肪变性（HS）是NAFLD的标志（2）。NAFLD可能在亚组中转变为慢性炎症（非炎症）。 酒精性脂肪性肝炎，NASH），并最终发展为肝硬化。HS在NAFLD的所有阶段都普遍存在。3-10% 美国所有儿童和40-70%的肥胖儿童患有HS（3）。大约有1500万肥胖者 美国的儿童（4），这意味着多达1000万青少年患有HS。儿科HS与 2型糖尿病（T2 D）、心血管疾病（CVD）和进行性肝病导致的过早死亡 在成年早期（5，6）。因此，儿童HS的成功治疗对于长期代谢和 心血管健康推荐的选择主要限于行为改变（即，减肥 和运动）和维生素E营养补充剂（3，5 -7）。没有FDA批准的药物用于 在任何年龄的个体中治疗NAFLD。 我们建议在青年HS患者中进行随机临床试验（RCT）。我们将扩大我们以前的 在一项研究中，用我们的基于必需氨基酸（EAA）的组合物（称为AMS 2392）治疗， 多囊卵巢综合征（PCOS）的发病机制 具体目标1。我们将研究用AMS 2392治疗8周将减少肝脏脂肪的假设 年轻人与HS我们将在48名13至18岁的男女青年中进行双盲RCT （坦纳4或5期），活检证实为HS。肝脏脂肪含量将通过磁共振测量 在开始时和8周干预后进行MRI检查。 具体目标2。我们提出，次要终点肝硬度，身体成分，胰岛素敏感性， 以及极低密度甘油三酯（VLDL-TG）、丙氨酸转氨酶（ALT）、ApoB 100 与安慰剂相比，在接受AMS 2392的组中肌酸酐和胰岛素敏感性将得到改善。 具体目标3。方案依从性将大于90%，并且在这些患者中不会发生不良事件 消耗AMS 2392，包括血浆谷胱甘肽浓度无变化。 完成本RCT将提供关于疗效、效应量、安全性和耐受性的信息， 将使我们能够成功地将AMS 2392作为医疗营养产品推向市场。