Attenuating Inflammation via Protein-Calorie Restriction

通过限制蛋白质热量减轻炎症

• 批准号: 7294344
• 负责人: TODD W RICE
• 金额: $ 15.11万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294344
• 关键词: Abdomen; Academic Medical Centers; Acute respiratory failure; Address; Adherence; Advanced Development; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Arginine; Aspiration Pneumonia; Atrophic; Attenuated; Bacteremia; Bacteria; Bacterial Translocation; Benefits and Risks; Biochemical; Biometry; Blood flow; Bolus Infusion; Burn Trauma; C-reactive protein; Caloric Restriction; Clinical; Clinical Research; Clinical Trials; Closed head injuries; Collaborations; Communities; Complication; Conduct Clinical Trials; Conflict (Psychology); Coupled; Critical Care; Critical Illness; Data; Development; Disruption; Doctor of Medicine; Enrollment; Enteral; Enteral Feeding; Enteral Nutrition; Enterobacteriaceae; Epidemiology; Epithelial; Epithelial Cells; Equilibrium; Feeds; Foundations; Functional disorder; Future; Gastrointestinal Motility; Glutamine; Growth; Homeostasis; Hyperglycemia; IL8 gene; Immune; Immunoglobulin A; Immunosuppression; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Inflammatory Response Pathway; Intensive Care; Intensive Care Units; Interleukin-1; Interleukin-10; Interleukin-4; Interleukin-6; Intestinal Mucosa; Intestines; Invasive; Ischemic Bowel Disease; Laboratories; Length of Stay; Leukotrienes; Measures; Mechanical ventilation; Mediator of activation protein; Medical; Mentors; Messenger RNA; Nausea and Vomiting; Nosocomial Infections; Nosocomial pneumonia; Numbers; Nutritional Support; Omega-3 Fatty Acids; Operative Surgical Procedures; Organ; Organ failure; Outcome; Parenteral Nutrition; Patient Recruitments; Patients; Physicians; Physiology; Population; Population Heterogeneity; Procedures; Production; Prostaglandins; Proteins; Purpose; Randomized; Randomized Controlled Trials; Rate; Reporting; Research; Research Personnel; Residual state; Residual volume; Resolution; Resources; Rice; Risk; Safety; Serum; Stimulus; Stomach; Structure; Systemic infection; Techniques; Therapeutic immunosuppression; Tight Junctions; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Upper arm; Ventilator; Weaning; aging population; bile salts; career; cellular microvillus; concept; cost; cytokine; day; design; feeding; gastrointestinal; gastrointestinal microvillus; human TNF protein; improved; in vivo; lipid metabolism; nutrition; outcome forecast; prevent; prognostic; prospective; response; skills; trial comparing

DESCRIPTION (provided by applicant): The purpose of this proposal is to cultivate the scientific development and advance the skills of Dr. Todd W. Rice in the design and conduct of clinical trials, so that he may become an independent investigator in conducting clinical research. Vanderbilt University Medical Center, through its several intensive care units, will provide Dr. Rice with the necessary patient population to conduct a prospective, randomized clinical trial comparing the effects of trophic nutrition versus advancement to full-calorie rates in mechanically ventilated, critically ill patients. Laboratory resources are available to investigate changes in biochemical responses, including pro- and anti-inflammatory cytokine responses. Differences in clinical outcomes, including weaning patients from the ventilator, will be assessed. Through collaboration with his clinical mentor, Dr. Arthur P. Wheeler, Dr. Rice will become adept at trial design, biostatistics, epidemiology, patient recruitment, and reporting of results to the scientific community. These skills will provide the foundation for Dr. Rice to pursue an independent academic career in critical care research. Many mechanically ventilated patients, unable to nourish themselves, are provided with nutrition, either enterally or parenterally. Enteral nutrition has been shown to reduce inflammation and improve clinical outcomes by preserving the intestinal mucosa, decreasing bacterial translocation, and reducing systemic infections. Although these improvements have been observed with full enteral feedings, very low rates of enteral feedings show similar protection in animals. We hypothesize that these low-level feedings also preserve the intestinal mucosa in ventilated patients, while reducing the pro- and anti-inflammatory cytokine responses seen in these patients along with the gastrointestinal complications, resulting in improved clinical outcomes compared to full-calorie feeds. The specific aims of this proposal are to demonstrate that low-level as compared to full-calorie enteral feedings will: 1) decrease the early pro-inflammatory and compensatory anti-inflammatory cytokine responses; 2) decrease the incidence of feeding complications, and thus, 3) improve clinical outcomes, such as ventilator-free days and other organ-failure free days. The aging population, increasing immunosuppression, and rising use of invasive procedures will result in the continued growth of critical care. Many mechanically ventilated, critically ill patients are supported with enteral nutrition. Despite widespread use, data on optimal delivery of enteral nutrition to such patients is lacking. This proposal will help weigh the benefits and risks, establish a cost-efficient means of reducing feeding complications, and provide the foundation for future studies of enteral feeds in patients with acute respiratory failure requiring mechanical ventilation.

描述（由申请人提供）： 本提案的目的是培养托德W博士的科学发展和提高技能。赖斯在设计和进行临床试验，使他可能成为一个独立的研究人员在进行临床研究。范德比尔特大学医学中心将通过其几个重症监护病房为Rice博士提供必要的患者人群，以进行前瞻性随机临床试验，比较营养营养与机械通气危重患者的全热量率的效果。实验室资源可用于研究生化反应的变化，包括促炎和抗炎细胞因子反应。将评估临床结局的差异，包括患者脱离呼吸机。通过与他的临床导师亚瑟P.惠勒博士的合作，赖斯博士将擅长试验设计、生物统计学、流行病学、患者招募和向科学界报告结果。这些技能将为Rice博士在重症监护研究中追求独立的学术生涯奠定基础。许多机械通气的病人，不能营养自己，提供营养，肠内或胃肠外。肠内营养已被证明可以通过保护肠粘膜、减少细菌移位和减少全身感染来减轻炎症并改善临床结局。虽然这些改善已被观察到与充分的肠内喂养，非常低的速率肠内喂养显示出类似的保护动物。我们假设，这些低水平喂养也保护了通气患者的肠粘膜，同时减少了这些患者沿着胃肠道并发症的促炎和抗炎细胞因子反应，与全热量喂养相比，改善了临床结局。该提案的具体目的是证明与全热量肠内喂养相比，低水平肠内喂养将：1）降低早期促炎和代偿性抗炎细胞因子反应; 2）降低喂养并发症的发生率，因此，3） 改善临床结果，如无呼吸机天数和无其他器官衰竭天数。老龄化 人口的增加、免疫抑制的增加和侵入性操作的使用的增加将导致重症监护的持续增长。许多机械通气的重症患者接受肠内营养支持。尽管广泛使用，但缺乏关于向此类患者提供最佳肠内营养的数据。这一建议将有助于权衡利益和风险，建立一个具有成本效益的方法，减少喂养并发症，并为未来的研究提供基础，急性呼吸衰竭患者需要机械通气的肠内喂养。