Clinical Center-COPD Clinical Research Network

临床中心-COPD临床研究网络

• 批准号: 6683761
• 负责人: STEVEN M SCHARF
• 金额: $ 79.16万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/6683761
• 关键词: Streptococcus pneumoniae vaccine; biomarker; biomedical facility; biotherapeutic agent; bronchodilators; chronic obstructive pulmonary disease; clinical research; clinical trials; comorbidity; cooperative study; corticosteroids; cytokine; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; immune tolerance /unresponsiveness; inflammation; inhalation drug administration; monoclonal antibody; patient oriented research; prednisolone; quality of life; respiratory disease /disorder therapy; respiratory disorder chemotherapy; respiratory pharmacology; training

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)： 慢性阻塞性肺疾病是一个世界性的重大问题，其发病率和发病率/死亡率都在不断上升。目前的治疗方法是戒烟、最大化肺功能、治疗感染和康复。对疾病基本机制的认识的增加为探索治疗这种疾病的新方法提供了机会。我们建议在马里兰大学建立一个临床中心，以参与NIH COPD临床研究网络。除了描述患者群体和招募策略外，我们还提出了两个模型建议供网络考虑。第一个建议基于最近的发现，即终末期COPD患者中存在强烈的炎症成分，可能导致体重减轻、肌肉萎缩和死亡率增加。一种关键的炎症细胞因子是肿瘤坏死因子α(TNFpha)。我们建议在三组随机双盲试验中评估抗肿瘤坏死因子α治疗(英夫利沙单抗)在中重度COPD患者中的效果。患者将接受26周的英夫利昔单抗、24周的英夫利沙单抗/12周的安慰剂或36周的安慰剂治疗。我们的主要结果将是6分钟步行距离，这是一种运动耐量的衡量标准。还将测量一些次要变量，包括痰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。第二项建议是关于在慢性阻塞性肺疾病中使用吸入性类固醇。以前的试验结果总体上令人失望。 然而，可能有一部分患者有反应。我们预测，具有明显呼吸道炎症成分的患者将可能对吸入类固醇产生反应，并将成为长期治疗的候选对象。我们将确定痰中促炎症细胞因子水平是否可以预测COPD患者对类固醇吸入剂的反应。我们将确定糖皮质激素受体中单核苷酸替代的存在是否对反应有负面影响。这项随机临床试验的结果将根据与健康相关的生活质量进行衡量。除了提出这些正式提案外，我们还制定了几个概念提案。我们还提供了COPD CRN健康成本利用核心的开发。