OMEGA-3 FISH OIL SUPPLEMENTS VERSUS PLACEBO IN NON-ALCOHOLIC STEATOHEPATITIS

OMEGA-3 鱼油补充剂与安慰剂治疗非酒精性脂肪性肝炎

• 批准号: 8167162
• 负责人: STEPHEN H CALDWELL
• 金额: $ 12.16万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167162
• 关键词: Adopted; Aftercare; American Heart Association; Animal Model; Behavior Therapy; Body Weight decreased; Cirrhosis; Communities; Computer Retrieval of Information on Scientific Projects Database; Coronary; Coronary heart disease; Data; Drug Formulations; European; Evaluable Disease; Exercise; Exercise Tolerance; Fatty Liver; Fatty acid glycerol esters; Fish Oils; Funding; Goals; Grant; Health; Hepatic; Human; Hyperlipidemia; Injury; Institution; Insulin; Insulin Resistance; Intervention; Life Style; Lipids; Liver; Magnetic Resonance Imaging; Measures; Medical; Metabolic syndrome; Multicenter Trials; National Center for Complementary and Alternative Medicine; Obesity; Omega-3 Fatty Acids; Patients; Pharmacological Treatment; Pilot Projects; Placebos; Polyunsaturated Fatty Acids; Population; Qualifying; Recommendation; Reducing diet; Relative (related person); Research; Research Personnel; Resources; Risk Reduction; Source; United States National Institutes of Health; Weight; base; blood lipid; conditioning; disorder risk; insulin sensitivity; meetings; nonalcoholic steatohepatitis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. The investiagors hypothesize that a one year course of 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. The investigators 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. Their 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. An additional secondary endpoint will involve a chi square analysis to evaluate the patients requiring initiation of anti-hyperlipidemic therapy in each of the two groups.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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。研究人员假设，与安慰剂相比，一年的 omega-3 脂肪酸（3 克/天）疗程将改善 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。研究人员选择了一个 omega-3 品牌，该品牌超过了欧洲和斯堪的纳维亚医学标准设定的纯度标记，并符合 NCCAM 最近采用的标准。他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。另一个次要终点将涉及卡方分析，以评估两组中每组中需要开始抗高血脂治疗的患者。