Mechanism Guided Therapy for Laryngopharyngeal Reflux

机制引导治疗咽喉反流

基本信息

批准号：
10212755
负责人：
Rena Hiren Yadlapati
金额：
$ 19.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-07 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10212755
关键词：
Accounting Address Adult Bioinformatics Biological Markers California Caring Chronic Clinical Clinical Data Clinical Management Clinical Trials Communities Controlled Clinical Trials Data Deglutition Disorders Devices Diagnosis Diagnostic Diagnostic Procedure Digestive System Disorders Disease Double-Blind Method Dysphonia Ensure Environment Esophageal Diseases Esophagus Expenditure Fluoroscopy Future Gastroesophageal reflux disease Generations Goals Grant Health Health Care Costs Healthcare Inferior esophageal sphincter structure Inflammation Infrastructure International Knowledge Larynx Light Manometry Measures Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Metagenomics Methods Modernization National Institute of Diabetes and Digestive and Kidney Diseases Observational Study Operative Surgical Procedures Oral Oral Characters Outcome Outcomes Research Pathway interactions Patient Care Patient-Focused Outcomes Patients Pepsin A Phenotype Physicians Physiological Physiology Proton Pump Inhibitors Randomized Randomized Controlled Trials Reflux Research Research Design Research Institute Research Personnel Research Training Resources Salivary Scientist Screening procedure Self-Help Devices Seminal Shotgun Sequencing Signs and Symptoms Source Symptoms Syndrome Techniques Testing Therapeutic Training Translational Research Treatment outcome United States National Institutes of Health Universities Upper Esophageal Sphincter Visit Voice Disorders Work arm authority base care burden career career development colorectal cancer screening constriction cost design diagnostic biomarker electric impedance experience gut microbiome health care service utilization improved indexing innovation laryngopharyngeal reflux microbial microbiome microbiome research microbiome sequencing multidisciplinary novel novel diagnostics novel therapeutics oral microbial community oral microbiome primary outcome ranpirnase recruit research facility response secondary outcome skills supportive environment targeted biomarker tool treatment strategy trial design validation studies

项目摘要

PROJECT SUMMARY/ABSTRACT Generalized approaches for laryngopharyngeal reflux (LPR), a prevalent and heterogeneous syndrome in which laryngeal symptoms are attributed to gastroesophageal reflux, have led to poor health outcomes, inappropriate resource utilization, and tremendous healthcare costs. As a physician scientist with advanced training in esophageal physiology and health outcomes research, my long-term career goal is to discover phenotype guided care paradigms for esophageal conditions, such as LPR, focused on distinct disease mechanism. My preliminary findings from single-arm clinical trials, observational studies, and initial translational research in LPR have generated the central hypothesis that novel diagnostic biomarkers can identify clinical-physiologic phenotypes of LPR and guide a mechanism focused treatment strategy. Thus, the research goals of this proposal are to (1) measure the efficacy of the novel therapeutic upper esophageal sphincter assist device in a rigorous biomarker targeted randomized sham-controlled trial of 78 subjects with salivary pepsin positive LPR, (2) identify phenotypes of LPR using latent class analysis of comprehensive physiologic and clinical data, and (3) compare oral microbiome between subjects with and without pepsin positive LPR. The research aims are aligned with my training goals to (1) develop expertise in advanced clinical trial methods, (2) acquire skills in phenotype design and latent class analysis, and (3) obtain experience with translational microbiome research. My outstanding and diverse mentorship team is overseen by primary mentor Dr. Samir Gupta, an expert clinical trialist that has contributed seminal discoveries in colorectal cancer screening. Co-mentors include Dr. John Pandolfino, a leading international authority and clinical researcher in esophageal physiology, and Dr. Bernd Schnabl, a physician scientist that has pioneered work in host effects on the intestinal microbiome. The exceptionally supportive and conducive institutional environment at University of California San Diego (UCSD) is a key strength of this application. UCSD’s NIH supported Clinical Translational Research Institute will provide cutting-edge clinical trial infrastructure. UCSD’s Center for Esophageal Diseases and Center for Voice & Swallowing Disorders will ensure successful subject recruitment and access to state-of-the-art diagnostic techniques. UCSD’s P30 supported Digestive Diseases Research Center directed by Dr. Bernd Schnabl, will provide leading resources in microbiomics and bioinformatics. Immediate anticipated impacts of this proposal are to inform the clinical management of LPR and shed light on a novel mechanistic pathway of inflammation in LPR, as well as enhance my career by providing unique skills in clinical trial methods and microbiome research. Ultimately, this career development proposal will launch my career as an impactful leader in multi-disciplinary clinical-translational research in the field of aero- digestive esophageal diseases.

项目概要/摘要喉咽反流 (LPR) 的通用方法，这是一种常见的异质综合征哪些喉部症状归因于胃食管反流，导致健康结果不佳，作为一名拥有先进技术的医师科学家，资源利用不当，以及巨大的医疗费用。食管生理学和健康结果研究方面的培训，我的长期职业目标是发现表型引导的食管疾病护理范例，例如 LPR，专注于不同的疾病我的初步发现来自单臂临床试验、观察性研究和初步研究。 LPR 的转化研究产生了一个中心假设：新的诊断生物标志物可以识别 LPR 的临床生理表型并指导以机制为重点的治疗策略。该提案的研究目标是（1）测量新型治疗上食管的疗效括约肌辅助装置在一项针对 78 名受试者的严格生物标志物随机假对照试验中唾液胃蛋白酶阳性 LPR，(2) 使用综合潜类别分析识别 LPR 的表型生理和临床数据，以及（3）比较使用和不使用胃蛋白酶的受试者之间的口腔微生物组积极的 LPR 研究目标与我的培训目标一致：(1) 发展高级专业知识。临床试验方法，(2) 获得表型设计和潜在类别分析的技能，(3) 获得经验我的优秀且多元化的导师团队由主要负责人监督。导师 Samir Gupta 博士是一位临床试验专家，在结直肠癌方面做出了开创性的发现共同导师包括 John Pandolfino 博士，他是该领域的国际领先权威和临床研究员。食管生理学和 Bernd Schnabl 博士是一位医学科学家，他在宿主效应研究方面处于领先地位大学的肠道微生物群异常支持和有利的制度环境。加州圣地亚哥分校 (UCSD) 是 UCSD 的 NIH 支持的临床应用的关键优势。转化研究所将为加州大学圣地亚哥分校的中心提供尖端的临床试验基础设施。食管疾病和声音与吞咽障碍中心将确保受试者招募成功并获得最先进的诊断技术 UCSD 的 P30 支持消化系统疾病研究。该中心由 Bernd Schnabl 博士领导，将提供微生物组学和生物信息学方面的领先资源。该提案的直接预期影响是为 LPR 的临床管理提供信息并阐明研究 LPR 炎症的新机制途径，并通过提供独特的方法来增强我的职业生涯最终，该职业发展建议将培养临床试验方法和微生物组研究方面的技能。作为航空领域多学科临床转化研究的有影响力的领导者，开启我的职业生涯消化道食道疾病。