Obtaining Samples from Human Subjects to Facilitate Basic, Translational and Clinical Research

从人类受试者身上获取样本以促进基础、转化和临床研究

• 批准号: 10928016
• 负责人: Michael Solomon
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10928016
• 关键词: Adult; American; American Heart Association; Antiphospholipid Antibodies; Arteriosclerosis; Ascorbic Acid; B-Lymphocytes; Basic Science; Biological Assay; Biology; Blood; Blood Vessels; Blood specimen; COVID-19; COVID-19 patient; Cardiology; Cell Line; Cell Separation; Clinical Research; Coagulation Process; Collaborations; Collection; Communicable Diseases; Critical Care; DNA; Development; Ebola virus; Enrollment; Evaluation; Fibrinolysis; Flow Cytometry; Generations; Genes; Genetic; Glycoproteins; Guidelines; Heart; Human; Immunophenotyping; In Vitro; Inflammation; Institution; Institutional Review Boards; Journals; Kinetics; Laboratories; Life; Lipopolysaccharides; Lung; Lymphocyte; Maintenance; Medicine; Molecular; Paper; Patients; Peripheral Blood Mononuclear Cell; Plasma; Plasma Cells; Protocols documentation; Publishing; Pulmonary Heart Disease; RNA; Relapsing polychondritis; Renal Replacement Therapy; Reporting; Research; Research Personnel; Research Subjects; Role; SYK gene; Sampling; Sepsis; Severity of illness; Therapeutic; Thrombelastography; Thrombosis; Translational Research; Ultrafiltration; United States National Institutes of Health; Urine; Vascular Diseases; Virus Shedding; Whole Blood; assay development; cell free DNA; clinical center; college; convalescent plasma; density; endothelial dysfunction; extracellular; granulocyte; healthy volunteer; human subject; induced pluripotent stem cell; inflammatory marker; member; neutrophil; new therapeutic target; novel marker; operation; pulmonary arterial hypertension; research study; response; symposium

This protocol defines in general terms the purposes for which blood, urine and ultrafiltrate will be collected from adult research subjects and healthy volunteers by members of the NIH Clinical Center's Critical Care Medicine Department and collaborating institutions and establishes general conditions under which sampling will be performed. Blood drawing will be consistent with NIH Clinical Center guidelines. The Critical Care Medicine Department and our associated investigators are involved in the development of new translational research protocols and maintenance of existing IRB approved research protocols. This protocol will support the establishment of new translational research protocols through assay development and provide information to guide the effective implementation of new protocols as well as maintain efficiency in operations of existing protocols. The protocol was approved by the National Heart, Lung, and Blood Institutional Review Board (recently changed to General Medicine 1 IRB) in August 2017. Over the course of the protocol, research subjects have provided blood samples for inflammatory marker studies, to characterize low density granulocytes as a novel therapeutic target for patients with sepsis, DNA gene sequencing for Pulmonary Arterial Hypertension (PAH), immunophenotyping for relapsing polychondritis, isolation of B cells for flow cytometry, cell free DNA isolation for PAH, thrombelastography (TEG) and other blood markers of coagulation and fibrinolysis, RNA isolation for sequencing, vitamin C levels, PBMCs isolated from whole blood for reprogramming and generation of induced pluripotent stem cell (iPSC) lines, and to isolate cells and plasma to either 1) serve as a comparator for COVID-19 patients or 2) perform in-vitro stimulations to study several COVID-19 molecular mechanisms. During the current reporting period 12 subjects were newly enrolled (9 healthy volunteers and 3 patients). Over the life of the protocol (as of September 2023) a total of 114 subjects have enrolled (65 healthy volunteers and 49 patients). Over the current reporting period 189 blood samples were provided to investigators and over the life of the protocol 677 samples have been provided to investigators. The following abstract have been presented using samples obtained from this protocol. Brusca SB, Elinoff JM, Jang MK, Demirkale CY, Valantine HA, Solomon MA, and Agbor-Enoh ST. Plasma Cell-free DNA as a Novel Marker of Disease Severity in Pulmonary Arterial Hypertension. American College of Cardiology 68thAnnual Scientific Session, J Am Coll Cardiol, 73(9, S1): S1897, 2019. Lu M, Blaine K, Cullinane A, Hall C, Dulau-Florea ,A, Sun J, Chenwi H, Graninger G, Harper B, Elinoff JM, and Solomon MA. Pulmonary Arterial Hypertension Patients Display Normal Kinetics of Clot Formation. American Heart Association Scientific Sessions, 140: A10714, 2019 Becicka W, Garrad E, Berreby G, Wang J, Nghiem K, Ramos-Benitez M, Cowling B, Moitra J, Huffstutler R, Carney K, Ferrante E, Cudrici C, Brofferio A, Tourdot B, Jacobson K, Knight J, Kanthi Y, and Boehm M. Genetic Deficiency of the Ectoenzyme CD73 Increases Neutrophil Extracellular Trap Formation in Patients with ACDC. Arteriosclerosis, Thrombosis, and Vascular Biology: Vascular Discovery Conference 2022 Becicka W, Berreby G, Wang J, Moitra J, Panicker S, Tourdot BE, Norris P, Kelly K, Zuo Y, Dumont L, Solomon MA, Knight JS and Kanthi Y. Antiphospholipid antibodies in COVID-19 Convalescent Plasma. Arteriosclerosis, Thrombosis, and Vascular Biology: AHA Vascular Discovery Conference 2022 Strich J, Chertow D, Ramos-Benitez, Marcos, and Warner S. SYK Inhibition Abrogates Neutrophil Hyperactivation in Response to Lipopolysaccharides. Critical Care Medicine, 51(1): 562, 2023. The following papers have been published using samples obtained from this protocol. Lu M, Blaine KP, Cuillinane A, Hall C, Dulau-Florea A, Sun J, Graninger GM, Harper BJ, Brusca SB, Elinoff JM, and Solomon MA. Pulmonary Arterial Hypertension Patients Display Normal Kinetics of Clot Formation. Pulm Circ, 11(3): 1-9, 2021 Strich RJ, Ramos-Benitez MJ, Randazzo D, Stein SR, Babyak A, Davey RT, Suffredini AF, Childs RW, Chertow DS. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic. The Journal of Infectious Diseases, 223 (6): 981984, 2021. Perez-Valencia LJ, Vannella KM, Ramos-Benitez MJ, Sun J, Abu-Asab M, Dorward DW, Awad KS, Platt A, Jacobson E, Kindrachuk J, Chertow DS (2023). Ebola virus shed glycoprotein is toxic to human T, B, and natural killer lymphocytes. iScience 26, 107323. https://doi.org/10.1016/j.isci.2023.107323

该协议一般术语定义了NIH临床中心重症监护医学部门的成员以及合作机构的成人研究对象和健康志愿者的血液，尿液和超滤的目的，并确定将在其中进行采样的一般条件。抽血将与NIH临床中心指南一致。 重症监护医学部和我们的研究人员参与了新的翻译研究方案的制定以及现有IRB批准的研究方案的维护。 该协议将通过测定开发来支持建立新的翻译研究协议，并提供信息，以指导有效实施新协议，并保持现有协议运营的效率。 The protocol was approved by the National Heart, Lung, and Blood Institutional Review Board (recently changed to General Medicine 1 IRB) in August 2017. Over the course of the protocol, research subjects have provided blood samples for inflammatory marker studies, to characterize low density granulocytes as a novel therapeutic target for patients with sepsis, DNA gene sequencing for Pulmonary Arterial Hypertension (PAH), immunophenotyping for relapsing polychondritis, isolation of B cells for flow cytometry, cell free DNA isolation for PAH, thrombelastography (TEG) and other blood markers of coagulation and fibrinolysis, RNA isolation for sequencing, vitamin C levels, PBMCs isolated from whole blood for reprogramming and generation of induced pluripotent stem cell (iPSC) lines, and to isolate cells and plasma to either 1) serve作为COVID-19患者的比较器或2）进行体外刺激以研究多种Covid-19分子机制。 在当前报告期间，有12名受试者是新招收的（9名健康志愿者和3名患者）。在该方案的寿命中（截至2023年9月），总共有114名受试者（65名健康志愿者和49名患者）。在当前的报告期间，向研究人员提供了189个血液样本，并在协议的寿命上向研究人员提供了677个样本。 已使用从该协议获得的样本提出以下摘要。 Brusca SB，Elinoff JM，Jang MK，Demirkale CY，Valantine HA，Solomon MA和Agbor-Enoh ST。肺动脉高压中疾病严重程度的新标志物等血浆细胞DNA。美国心脏病学院68年3月科学会议，J Am Coll Cardiol，73（9，S1）：S1897，2019。 Lu M，Blaine K，Cullinane A，C Hall C，Dulau-Florea，A，Sun J，Chenwi H，Graninger G，Harper B，Elinoff JM和Solomon MA。肺动脉高压患者表现出凝块形成的正常动力学。美国心脏协会科学会议，140：A10714，2019 Becicka W，Garrad E，Berreby G，Wang J，Nghiem K，Ramos-Benitez M，Cowling B，Moitra J，Moitra J，Huffstutler R，Carney K，Ferrante E，Cudrici C，Brofferio A，Brofferio A，Tourdot B，Tourdot B，Jacobson K，Jacobson K，Jacobson K，Knight J，Kanight J，Kanthi J，Kanthi Y，CD7 cd7 33 ACDC患者的中性粒细胞外陷阱形成。动脉硬化，血栓形成和血管生物学：血管发现会议2022 Becicka W，Berreby G，Wang J，Moitra J，Panicker S，Tourdot BE，Norris P，Kelly K，Kelly K，Zuo Y，Dumont L，Solomon L，Solomon MA，Knight JS和Kanthi Y.Antiphosphospholipid抗体在Covid-19 ColdeScentClescent Clasma中。动脉硬化，血栓形成和血管生物学：AHA血管发现会议2022 Strich J，Chertow D，Ramos-Benitez，Marcos和Warner S. Syk抑制作用废除了对脂多糖的响应中性粒细胞过度激活。重症监护医学，51（1）：562，2023。 使用从该协议获得的样本发表了以下论文。 Lu M，Blaine KP，Cuillinane A，C Hall C，Dulau-Florea A，Sun J，Graninger GM，Harper BJ，Brusca SB，Elinoff JM和Solomon MA。肺动脉高压患者表现出凝块形成的正常动力学。 Pulm Circ，11（3）：1-9，2021 Strich RJ，Ramos-Benitez MJ，Randazzo D，Stein SR，Babyak A，Davey RT，Suffredini AF，Childs RW，Chertow DS。 fostamatinib抑制Covid-19患者血浆诱导的细胞外陷阱：一种潜在的治疗性。 《传染病杂志》，223（6）：981984，2021。 Perez-Valencia LJ，Vannella KM，Ramos-Benitez MJ，Sun J，Abu-Asab M，Dorward DW，Awad KS，Platt A，Jacobson E，Jacobson E，Kindrachuk J，Chertow DS，Chertow DS（2023）。埃博拉病毒脱落的糖蛋白对人T，B和天然杀伤型淋巴细胞有毒。 Iscience 26，107323。https：//doi.org/10.1016/j.isci.2023.107323