Study B- cNEPTUNE

研究 B-c海王星

基本信息

批准号：
10251207
负责人：
DEBBIE S GIPSON
金额：
$ 53.63万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-08 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251207
关键词：
Adult Ancillary Study Behavior Biological Biological Markers Characteristics Child Child Health Childhood Chronic Kidney Failure Classification Clinical Clinical Research Clinical Trials Clinical Trials Design Communities Data Development Diagnosis Disease Disease Outcome Disease Progression End stage renal failure Enrollment Ensure Excretory function Exhibits Fostering Foundations Future Gene Expression Genetic Genetic Markers Genetic Variation Genomics Genotype Glomerular Filtration Rate Goals Home Immune Immunologics Investigation Kidney Knowledge Laboratories Laboratory Finding Link Longevity Longitudinal cohort Measurement Medical Genetics Methods Molecular Molecular Profiling Monitor Morbidity - disease rate Nephrotic Syndrome Organoids Outcome Participant Pathway interactions Patient Outcomes Assessments Patient-Focused Outcomes Patients Pediatric cohort Pharmacotherapy Phenotype Precision medicine trial Procedures Prognostic Marker Proteins Proteinuria Rare Diseases Renal function Renal glomerular disease Research Personnel Sampling Subgroup System Systems Biology Taxonomy Testing Time Translational Research Urine Validation base biomarker signature candidate identification clinical biomarkers clinical predictors clinical trial readiness cohort design disorder subtype genetic approach improved kidney biopsy mobile computing molecular marker novel optimal treatments patient stratification pediatric patients phenomics precision medicine precision medicine clinical trials prospective response risk variant standard of care therapeutic candidate therapeutic target tool trial design urinary

项目摘要

ABSTRACT Current approaches to childhood nephrotic syndrome (NS) are based on routine clinical and laboratory findings that are unable to accurately define the underlying biologic mechanisms, predict clinical course, or select optimal therapy. Treatment of childhood NS lacks a rational mechanistic basis and is associated with significant morbidity and is responsible for 12% of the pediatric end stage kidney disease in the USA. A precision medicine approach is warranted to identify mechanistically discrete disease subgroups, refine biomarkers to assist with molecular classification, identify relevant treatment targets, and improve trial design for pediatric NS. The children's nephrotic syndrome cohort in the Nephrotic Syndrome Study Network (Cohort B) is inclusive of 16 enrolling pediatric centers and associated investigators. In this project, Cohort B will expand to 200 children with incident NS, prospectively followed to define the longitudinal disease course, collect biospecimens to enable comprehensive molecular profiling (phenotype, genotype, immune profiling) for treatment target identification. cNEPTUNE will develop and improve clinical trial methods, endpoints, and systems to enable the conduct of precision medicine trials inclusive of children with nephrotic syndrome. In this renewal proposal, we propose to (a) define genotype-phenotype subgroups of children with incident NS; (b) define non-invasive biomarkers, inclusive of immunological profiles, in functionally defined subgroups of NS; (c) identify candidate therapeutic targets based on the mechanistically defined NS; and (d) develop validated endpoints, trial designs, and systems to foster efficient and effective precision medicine clinical trials for patients with NS.

抽象的目前治疗儿童肾病综合征 (NS) 的方法基于常规临床和实验室检查结果无法准确定义潜在的生物学机制、预测临床过程或选择最佳的治疗。儿童 NS 的治疗缺乏合理的机制基础，并且与显着的发病率相关美国 12% 的儿童终末期肾病是由该疾病引起的。精准医疗方法有必要识别机械上离散的疾病亚组，完善生物标志物以协助分子分类、确定相关治疗目标并改进儿科 NS 的试验设计。孩子们的肾病综合征研究网络中的肾病综合征队列（队列 B）包含 16 名入组者儿科中心和相关研究人员。在此项目中，B 组将扩大到 200 名发生事件的儿童 NS，前瞻性地跟踪以确定纵向病程，收集生物样本以启用用于识别治疗目标的综合分子分析（表型、基因型、免疫分析）。 cNEPTUNE 将开发和改进临床试验方法、终点和系统，以便能够进行包括肾病综合征儿童在内的精准医学试验。在本次更新提案中，我们建议 (a) 定义患有 NS 的儿童的基因型-表型亚组； (b) 定义非侵入性生物标志物，包括功能定义的 NS 亚组中的免疫学特征； (c) 确定候选治疗方法基于机械定义的 NS 的目标； (d) 开发经过验证的终点、试验设计和系统促进针对 NS 患者的高效精准医学临床试验。