AN ASSESSMENT OF INDUCED SPUTUM AS A TOOL TO EVALUATE ANTI-INFLAMMATORY AGENT

诱导痰的评估作为评估抗炎药的工具

• 批准号: 7377273
• 负责人: THOMAS W FERKOL
• 金额: $ 0.29万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377273
• 关键词: ASSESSMENT; INDUCED; SPUTUM; TOOL; EVALUATE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is a three-arm, multicenter, randomized, open-label, controlled, parallel-group trial comparing the effects of 28 days of ibuprofen, celecoxib, or no treatment on inflammatory markers in induced sputum obtained from subjects with mild to moderate CF lung disease. The study will measure changes in markers of lower airway inflammation in samples of induced sputum obtained before (Baseline Period), during (Treatment Period), and after (Recovery Period) treatment with ibuprofen or celecoxib in subjects with CF, and compare these changes with those observed in a control group of CF subjects who receive no anti-inflammatory treatment. The purpose for including the no treatment group is to define the variability of measurements performed on samples obtained by sputum induction (SI) and to serve as a control group for the ibuprofen and celecoxib treatment arms. Subjects in this ibuprofen arm will receive 20-30 mg/kg twice daily (maximum 3200 mg/day). Subjects in the celecoxib arm will receive 100 mg for weight 45 kg twice daily. The rationale for testing celecoxib in this study is based on its inhibition of COX-2, which occurs at fairly low plasma concentrations, and should be achievable with the upper limits of clinically acceptable doses chosen for this study. To confirm that adequate plasma concentrations of celecoxib were achieved in CF patients, pharmacokinetic studies of celecoxib are being obtained as part of this trial. In the vent that there is some unknown side effect of celecoxib at higher concentrations, the highest recommended dose in children was chosen for evaluation in this trial. Lower airway white cell count, PMN count, percentage of PMNs, active elastase, IL-8 and other cytokines (IL-6,TNF-., and IL-1.) will be measured in lower airway sputum samples. Subjects who are at least 10 years of age may be eligible for enrollment in the study. Induced sputum will be collected on 4 of 5 study visits. Two specimens will be collected prior to initiating therapy (Days 0 and 14), one specimen will be collected at the end of therapy (Day 42), and one specimen will be collected two weeks after therapy has stopped (Day 56). At each visit, the subject's vital signs, oximetry, and spirometry will be obtained before and after the SI procedure.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究是一项三组、多中心、随机、开放标签、对照、平行组试验，比较了28天布洛芬、塞来昔布或未治疗对轻度至中度CF肺病受试者诱导痰中炎症标志物的影响。本研究将测量CF受试者接受布洛芬或塞来昔布治疗前（基线期）、治疗期间（治疗期）和治疗后（恢复期）采集的诱导痰样本中下呼吸道炎症标志物的变化，并将这些变化与未接受抗炎治疗的CF受试者对照组中观察到的变化进行比较。纳入无治疗组的目的是定义对通过痰液诱导（SI）获得的样本进行测量的变异性，并作为布洛芬和塞来昔布治疗组的对照组。该布洛芬组的受试者将接受20-30 mg/kg每日两次（最大3200 mg/天）。塞来昔布组的受试者将接受100 mg，体重45 kg，每日两次。在本研究中测试塞来昔布的原理是基于其对考克斯-2的抑制作用，这种抑制作用在相当低的血浆浓度下发生，并且应该可以通过为本研究选择的临床可接受剂量的上限来实现。为了证实CF患者中达到了足够的塞来昔布血药浓度，本试验中进行了塞来昔布的药代动力学研究。由于塞来昔布在较高浓度下存在一些未知的副作用，因此本试验选择儿童最高推荐剂量进行评价。 下呼吸道白色细胞计数、PMN百分比、活性弹性蛋白酶、IL-8和其它细胞因子（IL-6、TNF-α、IL-10、IL-12、IL-14、IL-16、IL-18、IL-19和IL-1）。将在下呼吸道痰液样本中进行测量。年龄至少为10岁的受试者可能有资格入组本研究。将在5次研究访视中的4次访视时采集诱导痰。在开始治疗前（第0天和第14天）采集两份标本，在治疗结束时（第42天）采集一份标本，在治疗停止后两周（第56天）采集一份标本。每次访视时，将在SI手术前后获得受试者的生命体征、血氧测定和肺量测定。