Amino Acids and Pediatric Hepatic Steatosis

氨基酸和小儿脂肪肝

基本信息

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
项目类别：
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

项目摘要

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病 (NAFLD) 是北美最常见的肝脏疾病 (1)。肝的脂肪变性 (HS) 是 NAFLD 的标志 (2)。 NAFLD 可能在亚组中转变为慢性炎症（非非酒精性脂肪肝）酒精性脂肪性肝炎（NASH），最终发展为肝硬化。 HS 在 NAFLD 的各个阶段都很常见。 3-10%的美国所有儿童和 40-70% 的肥胖儿童都患有 HS (3)。大约有1500万肥胖者美国儿童 (4)，这意味着多达 1000 万青少年患有 HS。儿科 HS 与 2 型糖尿病 (T2D)、心血管疾病 (CVD) 和进行性肝病导致的过早死亡成年早期 (5,6)。因此，儿科 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（即减肥和锻炼）和维生素 E (3,5-7) 营养补充剂。目前还没有 FDA 批准的药物任何年龄个体的 NAFLD 治疗。我们建议对患有 HS 的青少年进行随机临床试验 (RCT)。我们将扩大我们之前的在一项研究中，使用我们基于必需氨基酸 (EAA) 的组合物（称为 AMS2392）进行治疗可减少肝脏损伤患有多囊卵巢综合症（PCOS）的青少年女性的脂肪。具体目标 1. 我们将研究 AMS2392 治疗 8 周会减少肝脏脂肪的假设患有 HS 的青少年。我们将对 48 名 13 至 18 岁的男女青少年进行双盲 RCT （Tanner 4 期或 5 期）具有活检记录的 HS。将通过磁共振测量肝脏脂肪含量在干预开始时和干预八周后进行成像（MRI）。具体目标 2. 我们建议次要终点是肝脏硬度、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)、ApoB100、与安慰剂相比，接受 AMS2392 组的肌酐和胰岛素敏感性将得到改善。具体目标 3. 方案遵守率将超过 90%，并且不会出现不良事件消耗 AMS2392，血浆谷胱甘肽浓度没有变化。完成该随机对照试验将提供有关功效、效应大小、安全性和耐受性的信息，将使我们能够成功地将 AMS2392 作为医疗营养产品进行营销。