Mechanism Guided Therapy for Laryngopharyngeal Reflux

机制引导治疗咽喉反流

基本信息

批准号：
10402877
负责人：
Rena Hiren Yadlapati
金额：
$ 19.23万
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/10402877
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.

项目摘要/摘要喉咽反射X（LPR）的广义方法，这是一种流行和异质综合征哪些喉符号归因于胃食管反射，导致健康状况不佳，不当的资源利用和巨大的医疗费用。作为先进的物理科学家在食管生理学和健康成果研究中培训，我的长期职业目标是发现诸如LPR之类的食管疾病的表型指导护理范例，重点是不同的疾病机制。我的初步发现来自单臂临床试验，观察性研究和初始发现 LPR的转化研究产生了一个中心假设，即新型诊断生物标志物可以确定LPR的临床生理表型，并指导以机制为中心的治疗策略。那，该提案的研究目标是（1）测量新型治疗上食管的效率严格的生物标志物针对78名受试者的随机假手术对照试验中的括约肌辅助装置唾液胃蛋白酶阳性LPR，（2）使用全面的潜在类别分析来识别LPR的表型物理和临床数据，（3）比较有和没有胃蛋白酶的受试者之间的口服微生物组正LPR。研究目标与我的培训目标保持一致（1）在高级方面发展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）获得经验通过翻译微生物组研究。我杰出而潜水的心态团队由小学负责导师Samir Gupta博士，专家临床试验员，在结直肠癌中贡献了第二个发现筛选。副官员包括约翰·潘多尔诺博士食管生理学和伯恩德·施纳布（Bernd Schnabl）肠道微生物组。大学的特殊支持和导电机构环境加利福尼亚州圣地亚哥（UCSD）是该申请的关键优势。 UCSD的NIH支持临床转化研究所将提供最先进的临床试验基础设施。 UCSD的中心食管疾病和语音和吞咽障碍中心将确保成功招募受试者并获得最新的诊断技术。 UCSD的P30支持消化疾病研究由Bernd Schnabl博士指导的中心将提供微生物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和Shed Light的临床管理提供信息在LPR中炎症的新型机械途径上，并通过提供独特的方式来增强我的职业生涯临床试验方法和微生物组研究的技能。最终，这个职业发展建议将启动我作为Aero-ofer-Aero-oper-Aero-dogipary临床翻译研究领域有影响力的领导者的职业消化性食管疾病。