Consortium of Eosinophilic Gastrointestinal Disease Researchers

项目总结(总体) 这一更新的应用旨在继续研究罕见的嗜酸性胃肠道疾病，重点是 嗜酸性食管炎(EoE)、嗜酸性胃炎(EG)、嗜酸性胃肠炎(EGE)和嗜酸性粒细胞 结肠炎(EC)通过嗜酸性胃肠道疾病研究人员联盟(CEGIR)进行。CEGIR将 促进高度协作、多站点、以患者为中心、转化性和临床研究，目的是 解决未得到满足的临床试验准备需求。CEGIR由俄亥俄州的临床中心(协调中心)组成， 科罗拉多州、阿肯色州、加利福尼亚州、伊利诺伊州、马里兰州、马萨诸塞州、明尼苏达州、纽约州、北卡罗来纳州 宾夕法尼亚州、田纳西州、德克萨斯州和犹他州。CEGIR的选址是根据他们的 在CEGIR第一个周期之前和期间彼此合作和成功的先前记录； 相关临床专业的丰富专业知识，包括胃肠病学、过敏、免疫学、营养学和 病理学；将儿科和成人患者整合到一个共同的联合体中的能力；良好的记录 在涉及这些患者群体的临床和翻译研究方面表现出色；以及出色的指导 影响早期受训人员职业发展的经验和能力。CEGIR网站拥有经过验证的访问权限 足够数量的EoE、EG、EGE和EC患者，从完成几个 涉及这些患者的对照临床试验。主动性患者权益倡导团体(PAG)，包括 美国嗜酸性粒细胞疾病伙伴关系和促进嗜酸性疾病研究的运动， 在CEGIR的背景下协同合作伙伴。虽然仍处于相对早期的阶段，但CEGIR正在展示 通过调查人员之间的协作互动取得成功(在职业发展的所有阶段，包括 代表下一代思想领袖的新成立的有前途的教员)，高度敬业 PAG和合作机构，并已成为专注于稀有EoE、EG、 EGE和EC.目前和拟议的CEGIR计划正在为这套罕见的 疾病，如建立准备参与的表型和基因分型较深的患者 在量化临床状态、内窥镜异常、组织病理学和 病人的幸福。在这个更新申请中，研究人员计划研究一个已经开发的观测项目 这为纵向分析提供了宝贵的机会。从这个队列中产生的数据有 已经证实了2型过敏性免疫(如IL-13)与EG的发病机制有关， 对这里描述的一项建议，即检查一种有希望的新型抗2型免疫的影响 治疗性(杜匹单抗、抗IL-4ra)。CEGIR包括变革性试点-可行性和职业提升 基于RDCRN内外协作的核心，将共同测试小说 假设，特别侧重于加强临床试验准备和吸引早期研究人员 从事罕见疾病研究的职业。

Project Summary (Overall) This renewal application aims to continue research on rare eosinophilic gastrointestinal diseases with a focus on eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). CEGIR will promote highly collaborative, multi-site, patient-centric, translational, and clinical research with the intent of addressing unmet clinical trial readiness needs. CEGIR comprises clinical centers in Ohio (coordinating center), Colorado, Arkansas, California, Illinois, Maryland, Massachusetts, Minnesota, New York, North Carolina, Pennsylvania, Tennessee, Texas, and Utah. The CEGIR sites have been carefully chosen on the basis of their pre-existing record of collaboration and success with each other before and during the first cycle of CEGIR; diverse expertise in relevant clinical specialties including Gastroenterology, Allergy, Immunology, Nutrition, and Pathology; the ability to integrate pediatric and adult patients into a common consortium; well-established record of excellence in clinical and translational research involving this patient population; and excellent mentorship experience and capacity to impact early stage trainees’ career development. CEGIR sites have proven access to an adequate number of patients with EoE, EG, EGE, and EC, as evidenced from completion of several controlled clinical trials involving these patients. Proactive patient advocacy groups (PAGs), including the American Partnership for Eosinophilic Disorders and the Campaign Urging Research for Eosinophilic Disease, partner synergistically in the context of CEGIR. Though still in a relatively early stage, CEGIR is demonstrating success via its collaborative interactions between investigators (at all stages of career development including newly established promising faculty who represent the next generation of thought leaders), highly engaged PAGs, and partnering institutions and has emerged into the leading research group focused on rare EoE, EG, EGE, and EC. Current and proposed CEGIR initiatives are developing clinical trial readiness for this set of rare diseases, such as the establishment of deeply phenotyped and genotyped patients who are ready to participate in research and emerging tools that quantify clinical states, endoscopic abnormalities, tissue pathology, and patient well-being. In this renewal application, investigators plan to study an already developed observational cohort of patients, providing a valuable opportunity for longitudinal analyses. Data emerging from this cohort has already substantiated the association of type 2 allergic immunity (e.g. IL-13) in the pathogenesis of EG, leading to a proposal, described herein, to examine the impact of a promising new anti-type 2 immunity therapeutic (dupilumab, anti-IL-4Ra). CEGIR includes transformative Pilot-Feasibility and Career Enhancement Cores based on collaboration across and outside of the RDCRN and which will collectively test novel hypotheses, particularly focused on enhancing clinical trial readiness and attracting early stage investigators for careers in rare disease research.