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）：本申请是为了响应 NHLBI RFA HL-02-029（哮喘临床研究网络 (ACRN)）而提交的，建议使用位于以下位置的临床、基因组、流行病学和基础科学资源的独特组合：维克森林大学 (WFU) 的肺科和重症监护医学部、克洛弗代尔肺临床研究中心、人类基因组学中心和公共卫生科学系，支持哮喘临床研究网络的临床站点。 我们提出了两套通用的具体目标，第一套描述了供 ACRN 考虑实施的两个具体协议，第二套致力于随着 ACRN 在第二个十年的发展而增加额外的资源和价值。 方案： 1) PAST 方案（针对持续性哮喘的吸入皮质类固醇/长效 β 受体激动剂组合的患者导向与标准治疗）将检验以下假设：使用患者调整剂量的吸入皮质类固醇/长效 β 受体激动剂进行患者导向治疗β-激动剂组合（布地奈德 160 微克/福莫特罗 4.5 微克）将以更低的成本提供改善的哮喘控制与标准的固定剂量联合治疗（每天两次喷吸布地奈德 160 微克/福莫特罗 4.5 微克，沙丁胺醇用作救援药物）相比，提高了患者满意度。 2) SAFE 方案（用抗 TNF、抗 IgE 和白三烯调节剂治疗严重哮喘）将检验以下假设：治疗严重哮喘患者（定义为使用氟替卡松 500 微克/沙美特罗 50 微克出现症状的患者） (Advair(R) 500/50) bid，与抗 IgE（奥马珠单抗）和/或抗 TNF（可溶性 TNF与白三烯受体拮抗剂（LTRA，孟鲁司特）治疗相比，Advair® 受体（依那西普）将提供更好的哮喘控制，并允许更多患者在抗 IgE 和/或抗TNF组，比白三烯受体拮抗剂组。我们还提供 WFU 资源和专业知识：1) 在人类基因组学中心，用于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、基因分型和单倍型分析候选基因，以及确定支气管镜检查样本中的基因表达水平； 2) 公共卫生科学部 (PHS) 确定的 a) 协助分析主要收集的数据 ACRN 协议回答可用数据集可能提出的“辅助”问题，b) 在 PHS 社会科学和公共卫生政策部门调查卫生经济学和以患者为中心的结果问题，特别是满意度和信任度； 3) 包含在我们的基础科学实验室内，用于开发和验证改进的气道炎症非侵入性生物标志物，用于多中心临床试验。