Redox Trapping for Biospecimen Preservation and Innovation in Sepsis Care

用于生物样本保存的氧化还原捕获和脓毒症护理创新

• 批准号: 10541870
• 负责人: Daniel Clark Files
• 金额: $ 22.74万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541870
• 关键词: Address; Affect; Age; Biochemistry; Bioinformatics; Biological Markers; Biology; Blood; Blood Preservation; Blood Specimen Collection; Blood specimen; Caring; Cell Membrane Permeability; Cells; Cessation of life; Chemicals; Clinical; Clinical Data; Clinical Trials; Collection; Critical Care; Critical Illness; Cryopreservation; Cysteine; Data; Data Analytics; Data Set; Dependence; Development; Disease; Disease Progression; Electrons; Enrollment; Ethnic Origin; Formulation; Freezing; Future; Gender; Human; Individual; Injury; Institution; Laboratories; Legal patent; Link; Mass Spectrum Analysis; Measurement; Mediator; Medicine; Metabolism; Methods; Modeling; Modification; Molecular; Multiomic Data; Organ failure; Outcome; Oxidation-Reduction; Patients; Performance; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Physiological; Pilot Projects; Plasma; Predisposition; Prevention; Procedures; Process; Proteins; Race; Reaction; Reactive Oxygen Species; Reagent; Recovery; Research; Research Personnel; Sampling; Sepsis; Site; Specimen; Staging; Technology; Testing; Time; Work; acute care; blood fractionation; clinical care; clinical diagnosis; clinical phenotype; cohort; data warehouse; design; effective therapy; forest; improved; innovation; interest; molecular marker; new therapeutic target; oxidation; preservation; prevent; prospective; response; sample collection; scale up; septic patients; sex; single cell technology; single-cell RNA sequencing; small molecule; standard of care; therapeutic development; tool; trial design

ABSTRACT We aim to advance sepsis research and clinical diagnosis by introducing a new redox trapping formulation for preservation of blood specimens. The new formulation is anticipated: 1) to prevent artifactual oxidation and loss of specimen integrity during storage, 2) to enable studies of redox metabolism which underlines the dysregulated immunometabolic response in sepsis, and 3) to improve analysis of differentiating redox molecular markers associated with demographic features (age, gender and racial ethnicity). Our combined expertise of redox biochemistry and innovation in patented redox chemical reagents, sepsis mechanisms, trial design and clinical expertise will be applied first to validate the new redox trapping formulation (R21 Phase) and then to scale-up by deploying this for collection of blood specimens at sites participating in the EMbedded Precision in Acute Care Trials (EMPACT) Network (R33 Phase). This is a newly formed network of premier critical care clinical trials sites designed to conduct precision clinical trials and discovery research in sepsis. Successful accomplishment of our aims will improve staging of septic patients and clinical precision research for discovery of new therapeutic targets for treatment of sepsis. More specifically, during the R21 Phase we will investigate the compatibility of the new redox formulation with high-end mass spectrometry and single cell technologies to evaluate its performance for measurement of redox and other biomarkers. The new formulation will be compared with current standard of care procedures for blood collection for clinical and research purposes (gold standard). To further validate this formula in sepsis patients, we will then evaluate its effects on standard clinical lab tests in a pilot study using prospectively collected paired single timepoint samples from critically ill patients with sepsis. We will further determine the advantage of redox trapping formulation by linking the measurements to physiologic and outcome data collected passively through the Wake Forest Critical Care Data Analytic Platform. Upon accomplishment of key metrics at the completion of R21 Phase, we will work with the EMPACT Network in the R33 Phase to collect blood specimens from 150 patients at 3 timepoints across the continuum of their disease progression using the standard methods and the new redox formulation. Analysis using high-end omics technologies will produce information-rich and redox-specific datasets, which will be integrated using bioinformatics approaches and linked to clinical data captured passively via the EMPACT data warehouse to generate new hypotheses for sepsis research. Lastly, we include a plan to share cryopreserved specimens, clinical and molecular data with investigators at the institution to support discovery or hypothesis-driven research through pilot mechanisms under the Center for Redox Biology and Medicine and Critical Illness, Injury and Research Recovery Research Center directed by MPIs Furdui and Files, respectively, and with outside investigators via EMPACT.

抽象的 我们的目标是通过引入一种新的氧化还原捕获制剂来推进脓毒症研究和临床诊断 血液标本的保存。新配方预计：1）防止人为氧化和损失 储存期间样本的完整性，2) 能够研究强调失调的氧化还原代谢 脓毒症中的免疫代谢反应，3) 改进氧化还原分子标志物的区分分析 与人口特征（年龄、性别和种族）相关。我们综合的氧化还原专业知识 生物化学和专利氧化还原化学试剂创新、败血症机制、试验设计和临床 首先将应用专业知识来验证新的氧化还原捕获配方（R21 相），然后进行扩大规模 通过部署该系统在参与急性护理中的 EMbedded Precision 的地点采集血液样本 试验 (EMPACT) 网络（R33 阶段）。这是一个新成立的主要重症监护临床试验中心网络 旨在针对脓毒症进行精准的临床试验和发现研究。我们的成功实现 目标将改善脓毒症患者的分期和临床精确研究，以发现新的治疗方法 败血症治疗的目标。更具体地说，在 R21 阶段，我们将研究以下兼容性： 新的氧化还原配方采用高端质谱和单细胞技术来评估其 测量氧化还原和其他生物标志物的性能。新配方将与现行配方进行比较 用于临床和研究目的的血液采集护理程序标准（金标准）。为了进一步 在败血症患者中验证该公式，然后我们将在试点中评估其对标准临床实验室测试的影响 研究使用前瞻性收集的脓毒症危重患者的配对单一时间点样本。我们将 通过将测量结果与生理和生理联系起来，进一步确定氧化还原捕获配方的优势 通过维克森林重症监护数据分析平台被动收集的结果数据。之上 在 R21 阶段完成后，我们将与 EMPACT 网络合作 R33 阶段，在 150 名患者整个疾病过程中的 3 个时间点采集血液样本 使用标准方法和新的氧化还原配方进行进展。使用高端组学进行分析 技术将产生信息丰富且特定于氧化还原的数据集，这些数据集将使用 生物信息学方法并与通过 EMPACT 数据仓库被动捕获的临床数据相关联 为脓毒症研究提出新的假设。最后，我们制定了共享冷冻标本的计划， 与机构研究人员一起提供临床和分子数据，以支持发现或假设驱动的研究 通过氧化还原生物学和医学以及危重疾病、伤害和疾病中心下的试点机制 研究恢复研究中心分别由 MPI Furdui 和 Files 指导，并与外部合作 调查员通过 EMPACT。