Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- To determine the effect of doxycycline on inflammatory biomarkers
研究概览
简要总结
Doxycycline is known to exhibit immune modulatory activities beyond its antibacterial effects. In particular, doxycycline is a potent inhibitor of matrix metalloproteinase 9, which is a protease derived largely from neutrophils. Recent studies demonstrate a significant correlation between pulmonary disease severity and sputum concentrations of MMP-9 in patients with CF. In addition, sputum MMP-9 levels are associated with airway remodeling in CF.
The goal of this study is to determine the therapeutic potential of doxycycline in modulating host airway inflammation in patients with CF. Specifically, the study will characterize the PK /PD of doxycycline, evaluate the safety of short term therapy, and explore the concentration effect relationship between doxycycline exposure and sputum biomarker levels.
详细描述
This study will consist of a prospective, open-label, randomized, controlled trial conducted in 24 patients with cystic fibrosis. Twenty subjects will be stratified in a 1:2 ratio based on baseline FEV1 into mild (> 70%) or moderate (40-70%) pulmonary disease in order to control for disease severity within each dose level. The subjects will be randomized in blocks of four to receive no drug, 40mg, 100mg, or 200mg daily for 28 days.
Sputum samples will be obtained in all groups by induction with hypertonic saline at baseline, 8, 24, and 48 hours following the first dose and then weekly for 4 weeks. Sputum will also be collected at two follow up visits after the treatment period at weeks 5 and 6.
In the doxycycline group, serial blood samples (5 mL) for determination of doxycycline concentrations will be obtained before and at 0, 0.5, 1, 2, 4, 12, 24, and 48 hours following the 1-hr infusion of a single IV dose. Once daily dosing of doxycycline will resume immediately following the 48-hour blood sample and will continue until day 28. Additional levels will be obtained pre-dose, and 1, 2, and 3 hours after doses administered on days 14 and 28. A sample of blood will be obtained at baseline, and at days 28 for inflammatory marker analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 18 years
- •Clinically stable (FEV1 within 10% of baseline)
- •FEV1 > 40% predicted
排除标准
- •Use of clinically significant concomitant drug therapy such as long-term use of nonsteroidal anti-inflammatory drugs or corticosteroids
- •Known hypersensitivity to doxycycline
- •Pregnancy or attempting to conceive, breast feeding, initiation of or change in hormonal method of contraception within 4 weeks of baseline or during the study
- •Use of systemic antibiotics (except oral azithromycin) within 4 weeks of baseline
- •Use of doxycycline within 60 days of baseline
- •Known history of gastrointestinal bleeding or gastrointestinal ulceration.
研究组 & 干预措施
Control
No doxycycline
干预措施: No doxycycline (Other)
Doxycycline
干预措施: Doxycycline (Drug)
结局指标
主要结局
To determine the effect of doxycycline on inflammatory biomarkers
时间窗: Within 42 days
次要结局
- To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis(Within 42 days)
研究者
Paul Beringer
Associate Professor
University of Southern California