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。项目摘要/摘要 非酒精性脂肪肝病（NAFLD）是北美最常见的肝病（1）。肝 脂肪变性（HS）是NAFLD（2）的标志。 NAFLD可能会在亚组中过渡到慢性炎症（非 - 酒精性脂肪性肝炎，NASH），最终用于肝硬化。 HS在NAFLD的所有阶段都普遍存在。 3-10％ 美国的所有儿童和40-70％的肥胖儿童均患有HS（3）。大约有1500万肥胖 美国的儿童（4），这意味着多达1000万年轻人患有HS。小儿HS与 由于2型糖尿病（T2D），心血管疾病（CVD）和进行性肝病的过早死亡 在成年初（5,6）。因此，成功治疗小儿HS是长期代谢和 心血管健康。建议的选项在很大程度上仅限于行为修改（即减肥 和运动）和维生素E（3,5-7）的营养补充剂。没有FDA批准的药物 在任何年龄的个体中对NAFLD的治疗。 我们建议在HS年轻人中进行随机临床试验（RCT）。我们将扩大以前的 研究我们的基本氨基酸（EAA）组成的研究称为AMS2392降低肝脏 青春期女性的脂肪患有多囊卵巢综合征（PCOS）。 具体目的1。我们将调查以下假设：用AMS2392进行8周的治疗将减少肝脏脂肪 在HS的年轻人中。我们将在13至18岁的48名男女青年中进行双盲RCT （坦纳阶段4或5）具有活检记录的HS。肝脂肪含量将通过磁共振测量 成像（MRI）在一开始和八周的干预之后。 具体目标2。我们建议肝刚度的次要终点，身体成分，胰岛素敏感性， 非常低密度甘油三酸酯（VLDL-TG），丙氨酸转氨酶（ALT），APOB100，APOB100， 与安慰剂相比，接收AMS2392的组将提高肌酐和胰岛素敏感性。 特定目的3。遵守协议将大于90％，并且在这些方面不会有不良事件 消耗AMS2392，包括血浆谷胱甘肽浓度没有变化。 此RCT的完成将提供有关功效，效果大小，安全性和容忍度的信息 将我们将成功销售AMS2392作为医疗营养产品。