Effect of Losartan on Progression of Emphysema

氯沙坦对肺气肿进展的影响

• 批准号: 9328147
• 负责人: Janet T. Holbrook
• 金额: $ 36.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9328147
• 关键词: Alveolar; Angiotensin Receptor; Angiotensins; Anti-Inflammatory Agents; Antihypertensive Agents; Apoptosis; Biological; Bronchial Spasm; Bronchodilator Agents; Cause of Death; Chronic Bronchitis; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Clinical Trials; Communities; Consent; Controlled Clinical Trials; Data Collection; Data Quality; Databases; Development; Diagnostic radiologic examination; Disease; Disease Progression; Epithelial; Exhibits; Goals; Heterogeneity; High Resolution Computed Tomography; Hospitalization; Individual; Institutional Review Boards; Interest Group; Leadership; Losartan; Lung; Manuals; Measures; Mediating; Mediator of activation protein; Monitor; Morbidity - disease rate; Multi-Institutional Clinical Trial; Mus; Neptune; Patients; Peripheral; Pharmaceutical Preparations; Pharmacology; Phenotype; Pilot Projects; Placebo Control; Placebos; Prevention; Procedures; Protocols documentation; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Randomized; Receptor Activation; Reporting; Research; Respiratory Muscles; Respiratory physiology; Safety; Scanning; Signal Transduction; Skeletal Muscle; Spirometry; Standardization; Structure; Structure of parenchyma of lung; Subgroup; Suggestion; System; Testing; Training; Transforming Growth Factor beta; United States; United States National Institutes of Health; X-Ray Computed Tomography; airway inflammation; cardiovascular risk factor; cigarette smoking; design; disability; distributed data; fibrillin; irbesartan; lung volume; mortality; muscle strength; pragmatic trial; pre-clinical; prevent; public health relevance; receptor; reduce symptoms; secondary analysis; smoking cessation; symptom treatment; treatment effect; web site

 DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death and disability in the United States. Current treatments target bronchospasm and inflammation of airways with the goal to reduce symptoms and prevent exacerbations. However, other than smoking cessation, no treatment has been found that modifies the progression of this disease. Moreover, COPD is a heterogeneous disease involving remodeling of both lung parenchyma (emphysema) and airways (chronic bronchitis). Research in mice exposed to cigarette smoke implicates TGF-beta signaling as a mediator of apoptosis that leads to emphysema. The development of emphysema can be prevented by blockade of the angiotensin-1 (AT1) receptor with drugs such as losartan. A pilot study of losartan in patients with COPD showed no overall improvement, but patients who had the emphysema phenotype demonstrated no progression of emphysema at 1 year compared to placebo treated patients who increased the percent of lung occupied by emphysema. These results did not reach statistical significance (p = 0.06) but were strongly suggestive of a benefit in COPD patients with emphysema. The aim of this proposal is to conduct a definitive randomized, placebo-controlled, clinical trial to test whether administration of 100mg/day of losartan to patients with radiographic evidence of emphysema will slow progression of their disease compared to comparable individuals given placebo. Emphysema progression will be measured by high-resolution computed tomography using standardized procedures. The trial is designed to be a highly-focused pragmatic trial with sparse data collection that can be accomplished in community as well as academic settings.

 描述（由申请人提供）：慢性阻塞性肺病（COPD）是美国死亡和残疾的主要原因，目前的治疗目标是减轻症状和预防病情加重。此外，COPD 是一种涉及肺实质（肺气肿）和肺组织重塑的异质性疾病。对接触香烟烟雾的小鼠进行的研究表明，TGF-β 信号传导是导致肺气肿的细胞凋亡的介质。可以通过使用药物（例如，血管紧张素 1）阻断来预防肺气肿的发生。氯沙坦治疗 COPD 患者的一项初步研究表明，与安慰剂相比，具有肺气肿表型的患者在 1 年时肺气肿没有进展。这些结果并未达到显着的统计学意义（p = 0.06），但表明对患有肺气肿的慢性阻塞性肺病患者有益处。本提案的目的是进行明确的随机治疗安慰剂。 - 对照临床试验，测试与服用安慰剂的可比个体相比，对有肺气肿放射学证据的患者服用 100 毫克/天氯沙坦是否会减缓其疾病进展。使用标准化程序进行高分辨率计算机断层扫描。该试验旨在成为一项高度集中的实用试验，可以在社区和学术环境中完成稀疏数据收集。