Clinical Trail 1

临床试验1

• 批准号: 10242129
• 负责人: GLENN T FURUTA
• 金额: $ 43.36万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242129
• 关键词: Adult; Age; Biological Markers; Biopsy; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Consensus; Data; Development; Diagnosis; Diagnostic; Disease; Endoscopy; Enrollment; Eosinophilic Colitis; Eosinophilic Esophagitis; Eosinophilic Gastritis; FDA approved; Foundations; Future; Gastrointestinal Diseases; Gene Expression Profile; Government Agencies; Guidelines; Histologic; Histology; Industry; Knowledge; Longitudinal cohort; Measures; Medical Research; Messenger RNA; Molecular; Molecular Disease; Molecular Medicine; Molecular Profiling; Natural History; Network Infrastructure; Outcome; Outcome Measure; Parents; Pathogenesis; Patient Outcomes Assessments; Patient Selection; Patients; Phenotype; Population; Prediction of Response to Therapy; Process; Publishing; Quality of life; Rare Diseases; Readiness; Research Personnel; Research Project Grants; Severities; Societies; Subgroup; Symptoms; Testing; Therapeutic Intervention; Therapeutic Trials; Time; Tissues; Transcript; Treatment outcome; clinical care; clinical outcome measures; clinical phenotype; clinical trial enrollment; clinical trial readiness; clinically significant; cohort; eosinophilic gastroenteritis; gastrointestinal; genome-wide; molecular marker; molecular phenotype; multidisciplinary; novel therapeutics; patient advocacy group; patient population; patient subsets; predictive marker; predictive panel; primary outcome; prospective; standard of care; systematic review; transcriptome; transcriptome sequencing; treatment response

Project Summary (Clinical Research Project: OMEGA2) Eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) are four distinct and rare diseases that have no FDA-approved treatments. These diseases are often collectively referred as eosinophilic gastrointestinal diseases (EGIDs). Our understanding of the pathogenesis of EGIDs has many gaps that include identification of predictors and biomarkers of longitudinal disease trajectory, understanding the molecular mechanisms and pathogenesis of these diseases, and defining relationships between transcriptional profiles and clinical phenotypes. The current standard of care (SOC) is repeated endoscopy with biopsy, and it is unclear whether biomarkers and patient-reported outcomes (PROs) can accurately function as surrogates for tissue histology. In the first cycle of the Consortium Eosinophilic Gastrointesinal Disease Researchers (CEGIR1), the longitudinal trial Outcome Measures for EGIDs across Ages (OMEGA1) filled important gaps in our knowledge. We identified relationships between PROs in children and their parents and the association of clinical outcome measures (COMs), including symptoms, endoscopy score, and quality of life (QOL) metrics, with histologic and molecular disease activity, focused on EoE. CEGIR elucidated distinct EoE endotypes and histologic and molecular commonalities and differences of EGIDs. In this second CEGIR cycle (CEGIR2), OMEGA2 proposes the overarching hypothesis that COMs and molecular biomarkers will associate with histologic features to allow accurate longitudinal phenotypic and clinical profiling of EGID patient populations. OMEGA2 will assess key issues for clinical trial readiness in EGIDs. Specifically, we aim to understand the COMs and transcriptome profiles that best reflect histologic disease courses to define and refine diagnostic criteria and outcome metrics for clinical trials. In Aim 1, we will determine the association between COMs and longitudinal disease courses. Using the existing and growing population of prospectively enrolled EGID patients, we will test the hypothesis that COMs, including PROs and endoscopic severity metrics, longitudinally correlate with histologic findings. We will determine whether COMs change over time and treatments and whether they correlate with EGID histology. In Aim 2, we will determine the association of EGID molecular profiles with phenotypes and outcomes. We will test the hypothesis that gastrointestinal mRNA transcript signatures longitudinally associate with clinical and histologic phenotypes, COMs, and treatment outcomes. We will determine whether diagnostic EG, EGE, and EC transcript panels predict treatment response and/or change with treatment. In Aim 3, we will establish diagnostic criteria and guidelines for EG, EGE, and EC using the COMs, endoscopic, histologic, and molecular data generated in OMEGA2 to conduct a formal consensus and guideline process. Collectively, we are proposing to further develop a longitudinal cohort of EGID patients that will answer fundamental questions concerning the natural history, disease definitions, and outcomes of these rare understudied diseases.

项目摘要（临床研究项目：omega2） 嗜酸性食管炎（EOE），嗜酸性胃炎（例如），嗜酸性粒细胞性胃肠炎（EGE）和嗜酸性粒细胞 结肠炎（EC）是未经FDA批准的四种独特且罕见的疾病。这些疾病通常是 统称为嗜酸性胃肠道疾病（EGID）。我们对发病机理的理解 Egids有许多差距，包括识别纵向疾病的预测因子和生物标志物 轨迹，了解这些疾病的分子机制和发病机理，并定义 转录曲线和临床表型之间的关系。当前的护理标准（SOC）是 重复进行活检的内窥镜检查，目前尚不清楚生物标志物和患者报告的结果（PROS）是否 可以准确地充当组织组织学的替代物。在财团的第一个周期中 胃疾病研究人员（CEGIR1），跨年龄段的EGID的纵向试验结果指标 （Omega1）填补了我们所知的重要空白。我们确定了儿童优缺点的关系， 他们的父母和临床结局指标的关联（COM），包括症状，内窥镜评分， 和组织学和分子疾病活性的生活质量（QOL）指标集中在EOE上。塞吉尔 阐明了不同的EOE内型，组织学和分子共同点以及EGID的差异。在这个 第二个Cegir循环（CEGIR2），Omega2提出了一个总体假设，即COMS和Molecular 生物标志物将与组织学特征相关联，以允许准确的纵向表型和临床分析 EGID患者人群。 Omega2将评估EGID临床试验准备就绪的关键问题。具体来说， 我们旨在了解最能反映组织学疾病课程的COM和转录组轮廓 并完善临床试验的诊断标准和结果指标。在AIM 1中，我们将确定协会 在COM和纵向疾病课程之间。前瞻性地使用现有和不断增长的人口 招募了EGID患者，我们将检验以下假设，即COM，包括专业和内窥镜严重程度指标， 纵向与组织学发现相关。我们将确定coms是否会随着时间的流逝而变化，并且 治疗以及它们是否与EGID组织学相关。在AIM 2中，我们将确定EGID的关联 具有表型和结果的分子谱。我们将测试胃肠道mRNA的假设 转录标志纵向与临床和组织学表型，COM和治疗相关联 结果。我们将确定诊断，例如EG，EGE和EC成绩单是否可以预测治疗反应 和/或治疗变化。在AIM 3中，我们将建立EG，EGE和EC的诊断标准和指南 使用COM，内窥镜，组织学和omega2产生的分子数据进行正式 共识和指南过程。总的来说，我们提议进一步发展纵向的EGID 将回答有关自然史，疾病定义和结果的基本问题的患者 在这些罕见的研究疾病中。