Asthma Clinical Research Network (ACRN)

哮喘临床研究网络 (ACRN)

• 批准号: 6677070
• 负责人: Stephen P Peters
• 金额: $ 80.05万
• 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/6677070
• 关键词: antiinflammatory agents; asthma; beta adrenergic agent; bronchodilators; bronchoscopy; clinical research; clinical trials; cooperative study; corticosteroid receptors; corticosteroids; dosage; 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)：本申请是应NHLBI RFA HL-02-029，哮喘临床研究网络(ACRN)提交的，建议使用位于维克森林大学(WFU)的独特的临床、基因组、流行病学和基础科学资源的组合，在肺和重症护理医学部，克洛弗代尔肺临床研究中心，人类基因组中心，和公共卫生科学部，支持哮喘临床研究网络的临床站点。我们提出了两套一般的具体目标，第一套描述了供ACRN考虑实施的两项具体议定书，第二套旨在随着ACRN在第二个十年的发展而努力增加额外的资源和价值。方案：1)过去的方案(吸入性皮质类固醇/长效β-激动剂联合治疗持续性哮喘的患者导向疗法与标准疗法的对比)将检验这样一种假设，即患者导向疗法使用患者调整剂量的吸入皮质类固醇/长效β-激动剂组合(布地奈德160微克/福莫特罗4.5微克)将以更低的成本改善哮喘控制，并提高患者满意度，与标准的固定剂量联合疗法(每天两次吸入布地奈德160微克/福莫特罗4.5微克，沙丁特罗作为抢救药物)。2)SAFE方案(用抗肿瘤坏死因子、抗IgE和白三烯调节剂治疗重度哮喘)将检验这样一种假设：与白三烯受体拮抗剂(LTRA，孟鲁司特)相比，用抗IgE(奥马珠单抗)和/或抗肿瘤坏死因子(可溶性肿瘤坏死因子受体，依那西普)治疗重症哮喘患者，定义为那些有症状的患者，用氟替卡松500微克/沙美特罗50微克(Advair(R)500/50)bid，将提供更好的哮喘控制，与白三烯受体拮抗剂组相比，在抗IgE和/或抗肿瘤坏死因子治疗组中，更多的患者可以使用Advair(R)减少氟替卡松100微克/沙美特罗50微克的剂量。我们还提供WFU资源和专业知识：1)在人类基因组学中心，用于确定患者的基因类型和单倍型，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，用于对候选基因进行测序，对候选基因进行基因分型和单倍型分析，以及确定支气管镜样本中的基因表达水平；2)在公共卫生科学部(PHS)进行鉴定，以a)协助分析在主要 ACRN协议用于回答可利用现有数据集提出的“辅助”问题，以及b)在PHS社会科学和公共卫生政策部门，以调查医疗经济学问题和以患者为中心的结果，尤其是满意度和信任度；以及3)在我们的基础科学实验室内，开发和验证改进的非侵入性呼吸道炎症生物标志物，用于多中心临床试验。