Development and Validation of test for Gastro-esophageal Reflux with Aspiration

胃食管反流抽吸测试的开发和验证

• 批准号: 8591417
• 负责人: Homer A Boushey
• 金额: $ 33.98万
• 依托单位: ARADIGM CORPORATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-05 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591417
• 关键词: Adverse effects; Alcohol or Other Drugs use; Biological Assay; Clinical Research; Collection; Cromoglicic Acid; Cromolyn Sodium; Cystic Fibrosis; Detection; Development; Diagnostic Procedure; Diagnostic tests; Doctor of Philosophy; Dose; Esophageal; Evaluation; Fluorescein; Future; Gastroesophageal reflux disease; Government; Hamman-Rich syndrome; Hospitals; Hour; Human; Ingestion; Intervention; Intestines; Laboratories; Legal patent; Liquid substance; Literature; Lung; Lung Transplantation; Lung diseases; Manometry; Measures; Methods; Monitor; Oral; Oral Administration; Oropharyngeal; Patients; Persons; Pharmaceutical Preparations; Phase; Pilot Projects; Preparation; Process; Quality Control; Radioactive; Radionuclide Imaging; Recovery; Recurrence; Reflex action; Reflux; Reporting; Research; Respiratory System; Respiratory tract structure; Saliva; Sampling; Secondary to; Sedimentation process; Simulate; Sleep; Solutions; Sphincter; Sputum; Stomach; Suspension substance; Suspensions; Testing; Urine; Validation; Waxes; analytical tool; aqueous; base; chemical stability; clinical practice; commercial application; particle; phase 2 study; public health relevance; tool; trend; young adult

DESCRIPTION (provided by applicant): Although recurrent microaspiration of refluxed gastric fluid ("GER with microaspiration") is suspected in the onset and course of many diseases of the lungs and airways, the lack of a non-invasive, direct test for its occurrence has hampered research on its importance. Complicating assessment is its nocturnal occurrence, when sleep interferes with protective reflexes. The tests currently available, esophageal manometry and 24h pH monitoring, or scintigraphy, are expensive, technically difficult and indirect, or involve radioactive material. We have identified two compounds poorly absorbed systemically after ingestion; both are approved for human use and have few side effects. One is well absorbed from the lungs and airways and excreted in urine. The other is not absorbed from the lungs and airways, but can be prepared in monodisperse insoluble particles. We accordingly propose to examine whether overnight oral administration of the first drug results in greater quantities being detected in urine from 10 patients thought to have recurrent GER with microaspiration than from 5 healthy controls. We also propose to examine in the same subjects whether administration of the second substance as a suspension of particles results in different quantities being detected in sputum collected overnight and induced the following morning. We will examine the concordance of the findings when the drugs are given together - the particles of the second substance suspended in a solution of the first. If this pilot study is promising, we will propose Phase II studies to refine the methods and examine them in larger numbers of subjects.

描述（由申请人提供）：尽管回流胃液（“带有微型诱惑的GER”）的复发微观激素是在许多肺和气道的许多疾病的发作和过程中，但缺乏对其发生的非侵入性，直接测试的缺乏，对其重要性进行了研究。当睡眠干扰保护性反射时，评估复杂性是其夜间发生的情况。当前可用的测试，食管测量和24H pH监测或闪烁显像是昂贵，技术困难且间接或涉及放射性材料。摄入后，我们已经确定了两种完全吸收的化合物。两者都被批准用于人类使用，几乎没有副作用。一个人从肺和气道中充分吸收，并在尿液中排出。另一个不是从肺和气道中吸收的，但可以在单分散的不溶性颗粒中制备。因此，我们建议检查一夜之间的口服药物是否会导致更多数量 在10例患者中检测到的尿液中，被认为具有微观诱饵的复发性GER比5个健康对照组中检测到。我们还建议在同一受试者中检查第二种物质作为颗粒悬浮液是否导致在一夜之间收集的痰液中检测到不同数量的悬浮液，并于第二天早晨诱导。我们将研究当药物一起给出的发现的一致性 - 第二种物质的颗粒悬浮在第一个溶液中。如果这项试验研究很有希望，我们将提出II期研究以完善这些方法并在大量受试者中进行检查。