RESULT Trial-REflux SUrgery in Lung Transplantation

结果 肺移植中的反流手术试验

• 批准号: 8144359
• 负责人: R Duane Davis
• 金额: $ 68.35万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-16 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144359
• 关键词: Acids; Acute; Allografting; Animal Model; Animals; Aspirate substance; Bile fluid; Breathing; Bronchiolitis Obliterans; Cessation of life; Chronic; Clinical Research; Clinical Trials; Data; Data Quality; Denervation; Development; Diagnostic tests; Environmental Exposure; Exclusion Criteria; Exposure to; Failure; Frequencies; Fundoplication; Future; Gastric Acid; Gastrins; Gastroesophageal reflux disease; Goals; Grant; High Prevalence; Immune response; Incidence; Inflammatory; Injury; Lead; Life; Lung; Lung Transplantation; Lung diseases; Medical; Methods; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Organ; Organ Donor; Organ Transplantation; Outcome; Patients; Pepsin A; Phase I Clinical Trials; Phase II Clinical Trials; Predisposition; Prevalence; Prevention; Procedures; Production; Proton Pump Inhibitors; Quality of life; Randomized; Randomized Clinical Trials; Reflux; Research; Research Institute; Risk; Rodent; Role; Sample Size; Sampling; Severities; Site; Solid; Staging; Stomach; Syndrome; Testing; Training; Transplant Recipients; Transplantation; United States National Institutes of Health; Work; abstracting; clinical practice; early onset; electric impedance; improved; lung allograft; lung injury; mortality; novel; phase 1 study; prevent; prospective; public health relevance; randomized trial

DESCRIPTION (provided by applicant): The long-term goal of these studies is to understand the role that repetitive environmental exposures have in causing lung allograft injury and to substantially improve patient survival and quality of life by preventing these exposures. We propose to develop a novel interventional study that will be a multicenter, randomized clinical trial of lung transplant recipients with gastroesophageal reflux disease (GERD) who will be randomized to either receive medical management focusing on preventing gastric acid production or to undergo surgical fundoplication focusing on preventing GERD related aspiration environmental exposure to improve lung allograft function. Extensive preliminary research in animal models and lung transplant recipeints have demonstrated that GERD induced aspiration is associated with acute and chronic rejection, loss of allograft function and increased survival. In early phase I trials, the strategy of preventing aspiration by performing a fundoplication appears to lessen rejection and improve allograft function and patient survival. This proposal, we have one broad aim, Develop a randomized study, RESULT (Reflux Surgery in Lung Transplantation ) to determine if prevention of GERD related aspiration by surgical fundoplication improves lung allograft function. We intend to develop and submit to the NIH at a future date a prospective, randomized, multi- center, phase II clinical trial managed by the Duke Clinical Research Institute in which lung transplant recipients demonstrated to have GERD as assessed by pH/impedance probe study will be randomized to either receive medical management with proton pump inhibitors for maximal acid suppression or undergo surgical fundoplication as barrier to prevent reflux of any gastric contents. The primary endpoint of the study will be development of BOS-1 or death. We will accomplish the above specific aim by: 1.) Further developing our current consortium of lung transplant investigative sites by creating standard procedures and training methods to decrease the start-up period and improve data quality. 2.) Acquiring both retrospective data (prospectively collected) and prospectively collecting BAL samples from our site consortium to explore the relationship between reflux (esophageal pH/impdeance testing), aspiration (BAL markers e.g. bile, gastrin, pepsin) and patient outcomes (e.g. BOS and survival) to optimize sample size determination and inclusion/exclusion criteria for the trial. (End of Abstract) PUBLIC HEALTH RELEVANCE: Lung transplant recipients suffer more rejection and worse survival than other solid organ recipients. It is highly likely that the lung's repetitive environmental exposures explain a substantial component of this difference. Strategies that reduce these environmental exposures such as fundoplication, are likely to substantially prolong both life and quality of life. Results from this planning grant will develop a future clinical trial that will substantially change practice and may have broad implications to many lung diseases.

描述（由申请人提供）：这些研究的长期目标是了解重复环境暴露在导致肺同种异体移植物损伤中的作用，并通过预防这些暴露来显著改善患者生存率和生活质量。我们建议开发一项新的干预性研究，这将是一项多中心、随机临床试验，在患有胃食管反流病（GERD）的肺移植受者中进行，这些受者将随机接受以预防胃酸产生为重点的药物治疗或接受以预防GERD相关吸入性环境暴露为重点的手术胃底折叠术，以改善肺移植物功能。在动物模型和肺移植方案中的广泛的初步研究表明，GERD诱导的误吸与急性和慢性排斥反应、同种异体移植物功能丧失和存活率增加有关。在早期I期试验中，通过胃底折叠术防止误吸的策略似乎可以减少排斥反应，改善同种异体移植物功能和患者生存率。我们的这项提议有一个广泛的目标，即开展一项随机研究，结果（肺移植中的反流手术），以确定通过手术胃底折叠术预防GERD相关误吸是否能改善肺移植功能。我们打算在未来的某个日期开发并提交给NIH一个前瞻性、随机、多中心，由杜克临床研究所管理的II期临床试验，其中肺移植受者经pH/阻抗探针研究将随机分为接受质子泵抑制剂药物治疗以达到最大抑酸效果或接受胃底折叠术作为屏障以防止胃底反流任何胃内容物本研究的主要终点将是BOS-1的发生或死亡。我们将通过以下方式实现上述具体目标：（1）通过创建标准程序和培训方法，进一步发展我们目前的肺移植研究中心联盟，以缩短启动期并提高数据质量。 2.）的情况。采集回顾性数据（前瞻性收集）并从我们的研究中心联盟前瞻性收集BAL样本，以探索反流（食管pH值/阻抗检测）、抽吸（BAL标志物，例如胆汁、胃泌素、胃蛋白酶）和患者结局（例如BOS和生存期）之间的关系，以优化试验的样本量确定和入选/排除标准。(End摘要） 公共卫生相关性：肺移植受者比其他实体器官受者遭受更多的排斥反应和更差的生存率。肺的重复环境暴露很可能解释了这种差异的重要组成部分。减少这些环境暴露的策略，如胃底折叠术，可能会大大延长生命和生活质量。这项计划拨款的结果将开发一项未来的临床试验，该试验将大大改变实践，并可能对许多肺部疾病产生广泛的影响。

项目成果

Is prevention the best treatment? CMV after lung transplantation.

预防是最好的治疗吗？

• DOI: 10.1111/j.1600-6143.2011.03837.x
• 发表时间: 2012
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Patel,N;Snyder,LD;Finlen-Copeland,A;Palmer,SM
• 通讯作者: Palmer,SM

Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid.

• DOI: 10.3109/01902148.2016.1139213
• 发表时间: 2016
• 期刊: Experimental lung research
• 影响因子: 1.7
• 作者: Leung JH;Chang JC;Foltz E;Bell SM;Pi C;Azad S;Everett ML;Holzknecht ZE;Sanders NL;Parker W;Davis RD;Keshavjee S;Lin SS
• 通讯作者: Lin SS

An assessment of human gastric fluid composition as a function of PPI usage.

• DOI: 10.14814/phy2.12269
• 发表时间: 2015-01-01
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Foltz E;Azad S;Everett ML;Holzknecht ZE;Sanders NL;Thompson JW;Dubois LG;Parker W;Keshavjee S;Palmer SM;Davis RD;Lin SS
• 通讯作者: Lin SS