Asthma Clinical Research Network (ACRN)

哮喘临床研究网络 (ACRN)

• 批准号: 7110369
• 负责人: Stephen P Peters
• 金额: $ 66.97万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110369
• 关键词: antiinflammatory agents; asthma; beta adrenergic agent; bronchodilators; bronchoscopy; clinical research; clinical trials; cooperative study; corticosteroid receptors; corticosteroids; dosage; eicosanoid receptor; gene expression; genetic susceptibility; glucocorticoids; human subject; human therapy evaluation; immunoglobulin E; inhalation drug administration; leukotrienes; patient care management; patient oriented research; pharmacogenetics; respiratory airflow measurement; respiratory disorder chemotherapy; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): This application, submitted in response to NHLBI RFA HL-02-029, the Asthma Clinical Research Network (ACRN), proposes to use the unique combination of clinical, genomic, epidemiological, and basic scientific resources located at Wake Forest University (WFU), in the Division of Pulmonary and Critical Care Medicine, the Cloverdale Pulmonary Clinical Research Center, the Center for Human Genomics, and the Department of Public Health Sciences, in support of a Clinical Site for the Asthma Clinical Research Network. We propose two general sets of Specific Aims, the first of which describes two specific protocols for consideration by the ACRN for implementation, and the second which strives to add additional resources and value as the ACRN evolves during its second decade. Protocols: 1) The PAST Protocol (Patient-Directed versus Standard Therapy with an Inhaled Corticosteroid/Long-Acting Beta-Agonist Combination in Persistent Asthma) will test the hypothesis that patient-directed therapy using patient adjusted doses of an inhaled corticosteroid/long acting beta-agonist combination (budesonide 160 mu g/formoterol 4.5 mu g) will provide improved asthma control at less cost with increased patient satisfaction than standard, fixed-dose combination therapy (2 puffs twice a day of budesonide 160 mu g /formoterol 4.5 mu g with albuterol used as the rescue medication). 2) The SAFE Protocol (Treatment of Severe Asthma with Anti-TNF, Anti-IgE, and a Leukotriene Modifier) will test the hypothesis that treatment of patients with severe asthma, defined as those symptomatic on fluticasone 500 mu g/salmeterol 50 mu g (Advair(R) 500/50) bid, with anti-IgE (omalizumab) and/or an anti-TNF (soluble TNF receptor, etanercept) will provide better asthma control than treatment with a leukotriene receptor antagonist (LTRA, montelukast), and permit Advair(R) dose reduction to fluticasone 100 mu g/salmeterol 50 mu g in more patients in the anti-IgE and/or anti-TNF groups, than in the leuktriene receptor antagonist group. We further offer WFU resources and expertise: 1) in the Center for Human Genomics for the determination of patient genotypes and haplotypes for genetic epidemiological analysis and pharmacogenetic studies, for DNA isolation and storage, for sequencing, genotyping and haplotyping candidate genes, and determination of levels of gene expression in bronchoscopy samples; 2) identified in the Department of Public Health Sciences (PHS) to a) assist in the analysis of data collected in main ACRN protocols to answer "ancillary" questions which could be posed with the available data sets, and b) in the PHS Division of Social Science and Public Health Policy to investigate issues of health economics and patient-centered outcomes, particularly satisfaction and trust; and 3) contained within our basic science laboratories to develop and validate improved non-invasive bio-markers of airway inflammation for use in multi-center clinical trials.

描述（由申请人提供）：本申请是响应NHLBI RFA HL-02-029，哮喘临床研究网络（ACRN）提出的，建议利用维克森林大学（WFU）的临床、基因组学、流行病学和基础科学资源的独特组合，包括肺和重症医学部、Cloverdale肺临床研究中心、人类基因组学中心和公共卫生科学系。以支持哮喘临床研究网络的临床站点。我们提出了两组一般的具体目标，第一组描述了ACRN考虑实施的两个具体协议，第二组努力在第二个十年中随着ACRN的发展增加额外的资源和价值。协议:1)过去方案（患者指导与标准治疗中吸入皮质类固醇/长效β激动剂联合治疗持续性哮喘）将检验患者指导治疗的假设，即使用患者调整剂量的吸入皮质类固醇/长效β激动剂联合治疗（布地奈德160 μ g/福莫特罗4.5 μ g）将以更低的成本改善哮喘控制，并提高患者满意度。固定剂量联合治疗（布地奈德160 μ g /福莫特罗4.5 μ g，每日2次，以沙丁胺醇为抢救用药）。2) SAFE方案（使用抗TNF、抗ige和白三烯调节剂治疗严重哮喘）将验证这样的假设，即使用抗ige （omalizumab）和/或抗TNF（可溶性TNF受体，依那西普）治疗严重哮喘患者，即使用氟替卡松500 μ g/沙美特罗50 μ g (Advair 500/50) bid，比使用白三烯受体拮抗剂（LTRA，孟鲁司特）治疗更好地控制哮喘。与白三烯受体拮抗剂组相比，抗ige和/或抗tnf组中更多的患者允许将Advair(R)剂量减少到氟替卡松100 μ g/沙美特罗50 μ g。我们进一步提供WFU的资源和专业知识：1)在人类基因组学中心确定患者基因型和单倍型，用于遗传流行病学分析和药物遗传学研究，用于DNA分离和存储，用于测序，基因分型和单倍型候选基因，以及测定支气管镜检查样本中的基因表达水平；2)在公共卫生科学部（PHS）确定a)协助分析主要收集的数据