Omega-3 Fish Oil for Nonalcoholic Steatohepatitis

Omega-3 鱼油治疗非酒精性脂肪性肝炎

基本信息

批准号：
7493771
负责人：
STEPHEN H CALDWELL
金额：
$ 17.03万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7493771
关键词：
2,4-thiazolidinedione Acids Adopted Adult Aftercare Agreement American Heart Association Animal Model Arachidonic Acids Behavior Therapy Betaine Blood flow Body Weight decreased Cell membrane Cirrhosis Communities Condition Coronary Coronary heart disease Cytokine Activation Data Diet Dietary Fatty Acid Drug Formulations Eicosapentaenoic Acid End Point Erythrocytes European Evaluable Disease Exercise Exercise Tolerance Family Fasting Fatty Acids Fatty Liver Fatty acid glycerol esters Fibrosis Fish Oils Goals Greenland Health Hepatic Human Hyperlipidemia Hypertriglyceridemia Inflammation Inflammatory Inflammatory Bowel Diseases Ingestion Injury Insulin Insulin Resistance Intake Intervention Life Style Linoleic Acids Linolenic Acids Lipid Peroxidation Lipids Liver Liver diseases Magnetic Resonance Imaging Measurement Measures Mediator of activation protein Medical Membrane Lipids Metabolic syndrome Metformin Multicenter Trials Muscle National Center for Complementary and Alternative Medicine Obesity Omega-3 Fatty Acids Patients Peripheral Personal Satisfaction Pharmacological Treatment Pharmacotherapy Phospholipids Pilot Projects Placebos Plasma Polyunsaturated Fatty Acids Population Primary carcinoma of the liver cells Probiotics Qualifying Recommendation Reducing diet Relative (related person)Reporting Research Personnel Rheumatoid Arthritis Risk Reduction Score Skeletal Muscle Source Standards of Weights and Measures Thiazolidinediones United States Food and Drug Administration Ursodeoxycholic Acid Vitamin E Weight bariatric surgery base blood lipid cell injury conditioning day diet and exercise dietary supplements disorder risk fitness indexing insulin sensitivity lymphotoxin beta non-alcoholic fatty liver nonalcoholic steatohepatitis orlistat programs success waist circumference

项目摘要

DESCRIPTION (provided by applicant): Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well-defined. Other forms of therapy include insulin sensitizing agents but no intervention is proven or uniformly accepted. Furthermore, interpretation of pharmacological treatment results is confounded by commonly recommended life-style changes voluntarily adopted by the patient. Polyunsaturated fatty acids, especially formulations rich in omega-3 fatty, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega 3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that omega-3 fatty acid (3g/day) will produce improvement in NASH activity, liver fat content, and lipid profiles independent of weight loss or exercise conditioning compared to a placebo. Among commonly used supplements, omega-3 rich fish oils stand out as having won endorsement from the American Heart Association and FDA approval for a qualified health claim in coronary risk reduction. We have chosen a brand of omega-3 that exceeds purity marks set by European and Scandanavian Medicinal Standards and meets recently adopted criteria set by NCCAM. Our primary endpoint is to assess changes in a composite score of NASH-induced liver injury relative to changes in exercise tolerance and weight. Other secondary endpoints include changes in liver fat content by MRI, blood lipid profile, insulin sensitivity and markers of the metabolic syndrome after treatment. Statistical analysis will be performed to assess the impact of weight loss and changes in exercise tolerance on the primary endpoint relative to omega-3 use. This GCRC-based pilot study of 50 evaluable subjects will establish a workable platform for multicenter trials to measure the relative impact of voluntary life-style modification on potentially effective pharmacological therapy in treating NASH.

描述（由申请人提供）：非酒精性脂肪性肝炎 (NASH) 发生在 2-3% 的美国人口中，并有 15-20% 的机会进展为肝硬化。它与肥胖、高脂血症和胰岛素抵抗密切相关。治疗通常包括建议增加锻炼和开始减肥饮食，但这些目标的实现情况各不相同，并且它们与药物干预相结合的相对效果尚未明确。其他形式的治疗包括胰岛素增敏剂，但没有任何干预措施被证明或被一致接受。此外，药物治疗结果的解释受到患者自愿采取的通常推荐的生活方式改变的影响。多不饱和脂肪酸，尤其是富含 omega-3 脂肪的配方，因其对高脂血症和降低冠心病风险的有益作用而被医学界广泛接受和认可。最近的数据表明，omega 3 脂肪酸可通过降低肝脏脂肪含量来改善人类和 NASH 动物模型中的肝脏脂肪变性。我们假设，与安慰剂相比，omega-3 脂肪酸（3 克/天）将改善 NASH 活性、肝脏脂肪含量和血脂状况，与体重减轻或运动调节无关。在常用的补充剂中，富含 omega-3 的鱼油脱颖而出，获得了美国心脏协会的认可和 FDA 的批准，成为降低冠心病风险的合格健康声明。我们选择的 omega-3 品牌超过了欧洲和斯堪的纳维亚医学标准规定的纯度标记，并符合 NCCAM 最近采用的标准。我们的主要终点是评估 NASH 引起的肝损伤综合评分相对于运动耐量和体重变化的变化。其他次要终点包括 MRI 检测的肝脏脂肪含量变化、血脂谱、胰岛素敏感性和治疗后代谢综合征标志物。将进行统计分析，以评估体重减轻和运动耐量变化对主要终点相对于 omega-3 使用的影响。这项基于 GCRC 的试点研究涉及 50 名可评估受试者，将为多中心试验建立一个可行的平台，以衡量自愿生活方式改变对治疗 NASH 的潜在有效药物治疗的相对影响。