权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
10393005
负责人：
STEPHEN John TEACH
金额：
$ 42.44万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
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/10393005
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 Observational Study Oral Outcome Participant Patients Pharmacy facility Placebos Production Protocols documentation Randomized Randomized Clinical Trials 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 Wheezing Work Youth aged allergic response anti-IgE asthma exacerbation asthma prevention atopy base cost cytokine data management experience falls healthy volunteer high risk host microbiome improved inner city innovation metatranscriptome microbiome minority children multidisciplinary multiple omics nasal microbiome next generation obesity-associated asthma omalizumab prevent recruit research study respiratory microbiome response success transcriptome transcriptome sequencing transcriptomics urban children urban setting

项目摘要

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.

利用我们机构多样化和经验丰富的研究人员基础，我们成功地领导了合作