Clinical Center-COPD Clinical Research Network

临床中心-COPD临床研究网络

基本信息

批准号：
7118268
负责人：
STEVEN M SCHARF
金额：
$ 67.53万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-15 至 2008-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease is a major problem worldwide with increasing prevalence and morbidity/mortality. Current therapy is based on smoking cessation, maximizing lung function, treating infection and rehabilitation. The increase in knowledge about basic disease mechanisms affords the opportunity to explore new methods for treating this disorder. We propose the development of a clinical center at the University of Maryland to participate in the NIH COPD Clinical Research Network. In addition to describing the patient population and recruitment strategies, we present 2 model proposals for consideration by the network. The first proposal relies on recent findings that there is a strong inflammatory component in patients with end-stage COPD which may lead to weight loss, muscle wasting and increased mortality. A key inflammatory cytokine is tumor necrosis factor alpha (TNFalpha). We propose evaluating the effects of anti-TNFalpha therapy (inflixamab) in moderate to severe COPD patients in a 3-arm randomized blinded trial. Patients will receive 26 weeks of infliximab, 24 weeks inflixamab/12 weeks' placebo or 36 weeks of placebo treatment. Our primary outcome will be 6 minute walking distance, a measure of exercise tolerance. A number of secondary variables including proinflammatory cytokines in sputum and blood, pulmonary physiological and metabolic outcomes, body composition and quality of life (QOL) indices will be measured as well. The second proposal is on the use of inhaled steroids in COPD. Results from previous trials have in general been disappointing. However, there are likely to be subsets of patients who respond. We predict that patients with a prominent airway inflammatory component to their disease will be likely to respond to inhaled steroids and would be candidates for long-term treatment. We will determine if the sputum level of proinflamamtory cytokines is predictive of the response to steroid inhalers in COPD. We will determine if the presence of a single nucleotide substitution in the glucocorticoid receptor has a negative impact on the response. Outcomes from this randomized clinical trial will be gauged in terms of health related QOL. In addition to presenting these formal proposals, we have developed several concept proposals. We have also offered the development of a health cost utilization core for the COPD CRN.

描述（由申请人提供）：慢性阻塞性肺部疾病是全世界的一个主要问题，患病率和发病率/死亡率增加。当前的治疗是基于戒烟，最大化肺功能，治疗感染和康复。关于基本疾病机制的知识的增加为探索治疗这种疾病的新方法提供了机会。我们建议在马里兰州大学建立一个临床中心，以参加NIH COPD临床研究网络。除了描述患者人数和招聘策略外，我们还提出了2个模型建议，以供网络考虑。第一个提案依赖于最近的发现，即终阶段COPD患者的炎症成分很大，这可能导致体重减轻，肌肉浪费和死亡率增加。关键的炎症细胞因子是肿瘤坏死因子α（TNFalpha）。我们建议在一项三臂随机盲试验中评估抗TNFALPHA治疗（英夫利acmab）对中度至重度COPD患者的影响。患者将接受26周的英夫利昔单抗，24周英夫利昔单抗/12周的安慰剂或安慰剂治疗36周。我们的主要结果是步行距离6分钟，这是运动耐受性的度量。也将测量许多次要变量，包括痰液和血液中的促炎细胞因子，肺部生理和代谢结果，身体成分和生活质量（QOL）指数。第二个建议是在COPD中使用吸入类固醇。总体而言，先前试验的结果令人失望。但是，可能有反应的患者子集。我们预测，患有突出气道炎症成分的患者可能会对吸入类固醇反应，并且是长期治疗的候选者。我们将确定Proinflamamtory细胞因子的痰液水平是否可以预测COPD中对类固醇吸入剂的反应。我们将确定糖皮质激素受体中单个核苷酸取代是否对反应产生负面影响。这项随机临床试验的结果将根据与健康相关的QOL进行评估。除了提出这些正式建议外，我们还提出了几个概念建议。我们还为COPD CRN提供了健康成本利用核心的开发。