District of Columbia Childhood Asthma in Urban Settings - Clinical Research Center

哥伦比亚特区城市环境中的儿童哮喘 - 临床研究中心

• 批准号: 10588214
• 负责人: William James Sheehan
• 金额: $ 43.18万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588214
• 关键词: Allergens; Allergic; Asthma; Bacteria; Basic Science; Bioinformatics; Biometry; Blood; Caring; Child; Childhood Asthma; Clinical; Clinical Data; Clinical Research; Computational Biology; Data; Disadvantaged; Disease; District of Columbia; Dose; Ecosystem; Epidemic; Event; Fostering; Future; Hour; Hypersensitivity; Immune response; Immunology; Infection; Inflammatory Response; Infrastructure; Institution; Institutional Review Boards; Interferon alpha; Intervention; Investigational Drugs; Laboratories; Leadership; Microbe; Modeling; Molecular; Moraxella; Morbidity - disease rate; Nose; Obesity; Observational Study; Oral; Outcome; Participant; Patients; Pharmacy facility; Placebos; Production; Protocols documentation; Randomized; Research; Research Personnel; Research Project Grants; Respiratory Tract Infections; Rhinovirus; Risk; Role; Sampling; Schools; Seasons; Secure; Serum; Severities; Site; Streptococcus; Subcutaneous Injections; System; Time; Up-Regulation; Upper Respiratory Infections; Urban Community; Urban Population; Viral; Virus; Virus Diseases; Wheezing; Work; Youth; aged; allergic response; anti-IgE; asthma exacerbation; asthma prevention; atopy; base; cost; cytokine; data management; experience; falls; healthy volunteer; high risk; improved; inner city; innovation; metatranscriptome; microbiome; minority children; multidisciplinary; multiple omics; nasal microbiome; next generation; omalizumab; participant retention; prevent; randomized, clinical trials; recruit; research study; respiratory microbiome; response; success; transcriptome; transcriptome sequencing; transcriptomics; urban children; urban setting

Leveraging our institution’s diverse and experienced investigator base, our success in leading collaborative and single-site randomized clinical trials (RCTs) and mechanistic and observational studies, and our access to a large population of urban, disadvantaged, and largely minority youth with asthma, we propose the District of Columbia’s Childhood Asthma in Urban Settings Clinical Research Center (DC CAUSE-CRC). It will implement network-wide research projects with a multi-disciplinary team of senior and junior investigators bringing diverse backgrounds in pediatric asthma, allergy and immunology, airway multi-omics, and computational biology. The proposed clinical leadership has repeatedly succeeded as top enrollers in multi-site asthma research collaboratives, and our institution houses the required infrastructure to facilitate CAUSE’s collaborative studies. For our site-specific project, we will build on the prior work of the Inner City Asthma Consortium (ICAC) and explore the mechanistic and clinical aspects of the paradigm-shifting use of a single dose of omalizumab in the fall season to prevent exacerbations. Specifically, while providing pilot clinical data for a possible future RCT, we will examine the interaction of the nasal microbiome and the nasal inflammatory responses during viral upper respiratory infections (URIs) with and without a single dose of anti-IgE. Working synergistically in exacerbation-prone urban youth, allergic sensitization, allergen exposure, and rhinovirus (and other viral) URIs trigger a strong Th2 response and asthma exacerbations that occur most frequently after school begins (the “September epidemic”). The ICAC has demonstrated that when administered across the entire fall season, omalizumab reduces the odds of exacerbations by >50%. Given the cost and complexity of this approach, however, and noting that serum levels of omalizumab rise following subcutaneous injection within a time frame sufficient to prevent a virally induced exacerbation (7-8 days), we propose an entirely new strategy: Omalizumab Before Onset of Exacerbations (OBOE). It is a pilot, non-therapeutic, mechanistic RCT of omalizumab or placebo administered within 72 hours of onset of an URI. Over three fall seasons, OBOE will randomize at least 100 youth aged 6-17 years with persistent asthma, high atopy, and a recent exacerbation. We will “capture” their URIs for 90 days after school starts, sampling their nasal airways twice (within 72 hours of URI onset and again in a window between 7-10 days after URI onset). Our specific aims are: (1) to be leaders in the collaborative studies of the CAUSE network while fostering the next generation of local institutional leadership for DC CAUSE-CRC; (2) to determine the relationship among the nasal airway microbiome, host transcriptome, and Th2 responses in children treated with single dose omalizumab or placebo at the onset of viral URIs; (3) to determine the relationship between host nasal airway antiviral interferon-α response with and without omalizumab given at the onset of a viral URI; and (4-exploratory): to determine the differences in clinical outcomes between intervention and control participants.

利用我们机构的多元化和经验丰富的研究人员基础，我们在领导合作方面的成功 和单中心随机临床试验（RCT）以及机制和观察性研究，以及我们获得 大量的城市人口，弱势群体，主要是患有哮喘的少数民族青年，我们建议 哥伦比亚城市儿童哮喘临床研究中心（DC CAUSE-CRC）。将实施 网络范围的研究项目，由高级和初级研究人员组成的多学科团队， 儿科哮喘、过敏和免疫学、气道多组学和计算生物学背景。的 在多中心哮喘研究中， 我们的机构拥有所需的基础设施，以促进CAUSE的合作研究。 对于我们的特定地点项目，我们将在内城哮喘联盟（ICAC）之前的工作基础上， 探索单剂量奥马珠单抗在糖尿病患者中使用的范式转变的机制和临床方面， 秋季，以防止病情加重。具体而言，在为未来可能的RCT提供试点临床数据的同时， 我们将研究病毒感染过程中鼻腔微生物组和鼻腔炎症反应的相互作用。 上呼吸道感染（URI），有和没有单剂量的抗IgE。协同工作， 易加重的城市青年、过敏性致敏、过敏原暴露和鼻病毒（和其他病毒）URI 引发强烈的Th 2反应和哮喘急性发作，最常发生在开学后（ “九月疫”）。廉政公署已证明，在整个秋季进行管理时， 奥马珠单抗将恶化的几率降低> 50%。考虑到这种方法的成本和复杂性， 然而，注意到皮下注射后奥马珠单抗的血清水平在一定时间范围内升高， 为了足以预防病毒引起的急性加重（7-8天），我们提出了一种全新的策略： 急性发作前的奥马珠单抗（OBOE）。这是一项先导性、非治疗性、机制性随机对照试验， 在URI发作的72小时内给予奥马珠单抗或安慰剂。在三个秋季，OBOE将 随机选择至少100名6-17岁的持续性哮喘、高度特应性和近期急性发作的青少年。 我们将在开学后90天内“捕获”他们的URI，并对他们的鼻气道进行两次采样（72小时内 在URI发作后7-10天的时间窗内再次进行）。我们的具体目标是：（1） 领导者在合作研究的原因网络，同时培养下一代的地方 DC CAUSE-CRC的机构领导;（2）确定鼻气道之间的关系 单剂量奥马珠单抗治疗儿童的微生物组、宿主转录组和Th 2应答， （3）确定宿主鼻气道抗病毒药物与抗病毒药物之间的关系 在病毒性URI发作时给予和不给予奥马珠单抗的干扰素-α应答;以及（4-探索性）： 确定干预和对照参与者之间临床结果的差异。