Prospective tReatment EffiCacy in IPF uSlng genOtype for Nac Selection (PRECISIONS) trial and Molecular Endophenotyping in Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases study

IPF 使用基因型进行 Nac 选择 (PRECISIONS) 试验和特发性肺纤维化和间质性肺疾病分子内表型研究的前瞻性治疗效果

• 批准号: 10021690
• 负责人: KEVIN R FLAHERTY
• 金额: $ 187.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10021690
• 关键词: Acetylcysteine; Achievement; Adherence; Adverse event; Archives; Biological; Biological Specimen Banks; Biometry; Budgets; Case Report Form; Characteristics; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Collection; Communication; Consent; Custom; Data; Data Collection; Data Coordinating Center; Data Set; Databases; Diagnosis; Diagnostic; Documentation; Ensure; Esapent; Faculty; Fostering; Foundations; Genotype; Goals; Information Dissemination; Infrastructure; Institutes; Interstitial Lung Diseases; Lead; Leadership; Lung; Methodology; Michigan; Molecular; Molecular Analysis; Molecular Genetics; Monitor; National Heart, Lung, and Blood Institute; Online Systems; Outcome; Pathogenesis; Patients; Pharmacogenomics; Phenotype; Play; Procedures; Process; Productivity; Prognosis; Proteomics; Protocols documentation; Provider; Pulmonary Fibrosis; Recording of previous events; Registries; Reporting; Reproducibility; Reproducibility of Results; Research; Research Design; Research Personnel; Risk; Role; Sample Size; Sampling; Science; Secure; Services; Site; Slide; Statistical Data Interpretation; Statistical Methods; System; TOLLIP gene; Teleconferences; Telephone Interviews; Testing; Time; TimeLine; Training; Treatment Efficacy; United States National Institutes of Health; Universities; Visit; antifibrotic treatment; base; biobank; clinical care; clinical research site; data management; database design; design; disease heterogeneity; endophenotype; experience; genetic variant; genome sequencing; idiopathic pulmonary fibrosis; meetings; multimodal data; novel; operation; patient registry; personalized approach; precision medicine; programs; prospective; recruit; safety study; success; tool; transcriptome sequencing; web site; webinar; whole genome

Despite being the most frequent and deadly of the interstitial lung diseases (ILD), Idiopathic Pulmonary Fibrosis (IPF) remains challenging to diagnose and treat. The diagnostic process for IPF relies on subjective interpretations of clinical data while current antifibrotic therapies employ a “one size fits all” paradigm. Our clinical collaborators have been at the forefront of developing `omics approaches to diagnose and define prognosis in ILDs. Importantly, they identified the first pharmacogenomic interaction suggesting that IPF patients with rs3750920 TOLLIP T/T genotype strongly benefited from use of N-Acetylcysteine (NAC). Our project leverages existing partnerships with the Pulmonary Fibrosis Foundation (PFF) Patient Registry and Biorepository studies. This group has recruited ILD patients who have provided extensive baseline phenotypic and longitudinal outcome data, biological samples and have consented to be re-contacted for future research. Our overall objectives are to 1) efficiently conduct a novel precision genotype-based IPF trial using PFF Clinical Care Network sites; and 2) molecularly characterize a broad range of ILDs and identify genetic variants associated with IPF risk. An experienced Data Coordinating Center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan Statistical Analysis of Biomedical and Educational Research (SABER) unit in a top-ranked Department of Biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, research design, project management, study monitoring, database design and data management, and research administration. SABER has a strong track record of collaborations with the participating pulmonary investigators in the Clinical Coordinating Center (CCC) and clinical sites. The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims: (1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze and disseminate research findings; (2) Ensure the collection of timely, accurate and reproducible data, and maximize adherence to the study protocol; and (3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders. Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on “precision medicine era” IPF diagnosis, and benefits of a “precision” approach with a genotype-driven clinical trial.

尽管特发性肺病是最常见和致命的间质性肺病（ILD），但特发性肺病 纤维化（IPF）的诊断和治疗仍然具有挑战性。 临床数据的解释，而目前的抗纤维化治疗采用"一种尺寸适合所有"的范例。我们 临床合作者一直站在发展"组学"方法的最前沿， ILD的预后。重要的是，他们确定了第一个药物基因组学相互作用，表明IPF 具有rs3750920 TOLLIP T/T基因型的患者从N-乙酰半胱氨酸（NAC）的使用中强烈受益。我们 该项目利用了与肺纤维化基金会（PFF）患者登记处的现有合作伙伴关系， 生物储藏研究。该组招募的ILD患者提供了广泛的基线表型， 和纵向结果数据，生物样本，并同意为未来的研究重新联系。 我们的总体目标是：1）使用PFF有效地进行一项新的基于精确基因型的IPF试验 临床护理网络网站;和2）对广泛的ILD进行分子表征并识别遗传变异 与IPF风险相关。一个经验丰富的数据协调中心（DCC），具有强大的统计领导能力， 专业知识是设计和分析的关键，特别是在进行过程中出现意外问题时， 临床试验。密歇根大学生物医学和教育研究统计分析 （SABER）单位在生物统计学的顶级部门将担任DCC，汇集了经验丰富的 一组生物统计学，研究设计，项目管理，研究监测，数据库的教职员工 设计和数据管理以及研究管理。SABER拥有强大的合作记录 与临床协调中心（CCC）和临床研究中心的参与肺部研究者一起。的 UM DCC的总体目标是与研究者、CCC和NHLBI合作， 按时并在预算范围内成功完成研究。我们将通过以下方式实现这些目标： 三个具体目标：（1）通过提供统计和临床试验方法来提高科学严谨性 设计、分析和传播研究成果的专业知识;（2）确保及时、准确地收集 和可重复的数据，并最大限度地遵守研究方案;和（3）提供既定的 研究管理和操作以及研究间沟通的基础设施和服务 持份者我们的领导力、经验和专业知识将促进合作，鼓励科学研究， 生产力，并促进及时传播"精准医学时代" IPF诊断结果，以及 基因型驱动的临床试验的"精确"方法的好处。