EPA & DHA IN CRITICALLY ILL PATIENTS WITH SEPSIS AND CONTROLS

美国环保局

基本信息

批准号：
7952130
负责人：
Renee D Stapleton
金额：
$ 4.01万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7952130
关键词：
18 year old Accounting Acids Acute Lung Injury Affect Animal Model Anti-Inflammatory Agents Anti-inflammatory Blood Blood specimen Caring Cells Clinical Research Communities Computer Retrieval of Information on Scientific Projects Database Critical Illness Development Dose Drug Kinetics Eicosapentaenoic Acid Enrollment Enteral Financial cost Fish Oils Foundations Funding Grant Human Immune Inflammation Inflammatory Response Institution Intensive Care Units Kinetics Knowledge Lead Liquid substance Measurement Mechanical Ventilators Morbidity - disease rate Omega-3 Fatty Acids Oral Patient Care Patients Pharmacology Property Protocols documentation Recruitment Activity Research Research Personnel Resources Risk Risk Factors Sepsis Societies Source Specific qualifier value Syndrome Time Treatment Protocols United States National Institutes of Health Work healthy volunteer improved mortality prevent

项目摘要

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. Acute lung injury (ALI) is a common and devastating syndrome seen in critically ill patients with over 200,000 cases per year in the US alone. It is associated with high mortality (40% of patients with ALI die) and morbidity, and the financial cost to society is tremendous. Sepsis is the most common risk factor for ALI, accounting for 79% of cases. Only one treatment, using low breath volumes on the mechanical ventilator, has ever been shown to modestly improve survival from ALI, and there are no available therapies known to prevent ALI. New therapies aimed at preventing the development of ALI in patients at risk for the syndrome are desperately needed. Eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), the two omega-3 fatty acids found in fish oil, have multiple anti-inflammatory properties and are a promising new treatment for patients with existing ALI that we and others are studying. There is also exciting plausible biologic rationale for EPA and DHA as a preventative treatment for ALI: 1) in healthy volunteers, EPA and DHA decrease the same types of inflammation that lead to ALI, and 2) EPA and DHA ameliorate the development of ALI in animal models. Work investigating EPA and DHA as a preventative therapy for ALI in humans has not been performed before and, if effective, would represent a monumental leap forward in the care of patients at risk for ALI. However, there are substantial gaps in knowledge of this agent that must be filled before we can proceed with large human trials. For instance, we currently do not know the pharmacokinetics of EPA and DHA in critically ill patients; thus it is unclear how to properly dose the agent. Furthermore, we only have limited understanding of how fish oil might affect the function of circulating immune cells in patients with sepsis who are at risk for, but have not yet developed, ALI. This study defines the pharmacokinetics of EPA and DHA in sepsis patients at risk for ALI compared to healthy controls and investigates the hypothesis that EPA and DHA likely have different kinetics in critically ill patients than in healthy patients. We will also investigate whether administration of EPA and DHA modulates the responses of inflammatory cells in the blood in both patients with sepsis at risk for ALI and in healthy volunteers. All critically ill patients in this study have sepsis but have not yet developed ALI. They are 18 years old and cared for in an intensive care unit. Once patients are enrolled, they will undergo baseline blood sampling. They receive enteral liquid fish oil in a specified dosing regimen for 7 days, during which time they undergo serial blood draws for pharmacokinetic measurements. They then undergo a 7-day period of "washout" during which no fish oil is given but pharmacokinetic measurement continue. Healthy controls are also 18 years old and are recruited from the community. They receive the same oral fish oil dosing regimen (except in capsular form) as the critically ill patients and will have their blood draws according to the same protocol. This research is the first to investigate fish oil as a therapy to prevent acute lung injury in patients at risk and sets the foundation for larger studies. It rigorously defines the pharmacology of EPA and DHA in critically ill patients while investigating the mechanism of action using obtained blood samples.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。仅在美国，急性肺损伤（ALI）是一种常见且破坏性的综合症，仅在美国，每年超过20万例。它与高死亡率（40％的Ali死亡患者）和发病率有关，社会的财务成本巨大。败血症是ALI的最常见危险因素，占病例的79％。仅在机械呼吸机上使用低呼吸量的一种治疗方法已被证明可以适度改善Ali的生存，并且尚无可用的疗法可预防ALI。迫切需要旨在防止有综合症风险患者的ALI发展的新疗法。 Eicosapentaenoic酸（EPA）和二十二烷酰己酸（DHA）是鱼油中发现的两个omega-3脂肪酸，具有多种抗炎特性，对于我们和其他人正在研究的现有ALI患者来说，是一种有希望的新治疗方法。 EPA和DHA作为ALI的预防疗法也有令人兴奋的合理生物原理：1）在健康的志愿者中，EPA和DHA降低了导致ALI的相同类型的炎症，以及2）EPA和DHA在动物模型中的ALI的发展。研究EPA和DHA作为对人类ALI的预防疗法的工作尚未在之前进行，如果有效，将代表着有ALI风险的患者的巨大飞跃。但是，在我们可以进行大型人类试验之前，必须填补这一代理的知识差距。例如，我们目前不知道重症患者的EPA和DHA的药代动力学；因此，目前尚不清楚如何正确剂量剂量。此外，我们只了解鱼油如何影响败血症患者有可能但尚未发育的败血症患者的循环免疫细胞功能。这项研究定义了与健康对照组相比，败血症患者的EPA和DHA的药代动力学，并调查了EPA和DHA在重症患者中可能具有与健康患者不同的动力学的假设。我们还将调查EPA和DHA的给药是否调节两名患有ALI和健康志愿者风险的败血症患者的血液中炎症细胞的反应。这项研究中的所有重症患者均患有败血症，但尚未出现ALI。他们今年18岁，在重症监护室受到照顾。一旦入学，他们将接受基线血液采样。他们在特定的给药方案中接受肠道液体鱼油7天，在此期间，他们进行了连续的血液进行药代动力学测量。然后，他们经历了为期7天的“洗涤”期，在此期间没有给出鱼油，但药代动力学测量仍在继续。健康控制也有18岁，并从社区招募。他们接受与重症患者相同的口服鱼油剂量方案（囊状形式除外），并且会根据相同的方案获得血液。这项研究是第一个研究鱼油作为预防危险患者急性肺损伤的疗法，并为大型研究奠定了基础。它严格地定义了重症患者的EPA和DHA的药理学，同时使用获得的血液样本研究了作用机理。