In Situ Analysis of Sputum-derived Cellular Targets After Xolair (Omalizumab).
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma
研究概览
简要总结
The primary purpose of this study is to identify additional mechanisms of action of omalizumab that will lead to improved stratification of patients for treatment. Understanding the response of specific innate immune effector cells in the lung can provide clues to these questions. Investigators will use non-invasive measures of a discrete cell population to examine the downstream effects of omalizumab treatment in the lung. Information derived from these studies will help clarify mechanisms of action of omalizumab and help identify potential tools for patient endotyping and stratification for therapeutic interventions.
详细描述
This is a randomized, placebo-controlled, double blind, 16-week intervention study to show feasibility and proof of concept. Analysis of whole induced sputum is under development for endotyping for asthma, allowing sampling of rare cells from conducting airways, repeated sampling, and cell-specific detailed genomic evaluation. Investigators have developed a novel technique to simultaneously enrich innate immune cells from sputum. This technique allows for in situ analyses of sputum-derived human bronchial epithelial cells (sHBEC). The non-invasive nature of the technique provides a unique tool for in vivo human studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Physician diagnosed asthma
- •Lung function (one or more of the following documented in the 5 years before enrollment or demonstration during screening)
- •Bronchial hyper responsiveness (BhR) confirmed by ≥ 12% improvement in FEV1 post bronchodilator within the previous 5 years, or
- •Methacholine PC20 < 16mg/dl within the previous 5 years
- •Severity Criteria: Moderate-persistent asthma defined by the American Thoracic Society (ATS)
- •Asthma Control: Partly or uncontrolled asthma according to GINA 2012 guidelines (at least three of the following features: daytime symptoms more than 2 times/week, limitation of activities, nocturnal symptoms, need for rescue inhaler > 2 times/week, FEV1 <80% predicted)
- •Stable use of moderate-high dose inhaled corticosteroids in previous 3 months (definition derived from GINA 2012 guidelines: e.g. fluticasone propionate >250 mcg/day, budesonide > 400mcg/day)
- •Ability to perform induced sputum maneuvers
- •Presence of elevated allergen IgE to any perennial aeroallergen
排除标准
- •Pulmonary function: FEV1 ≤ 70% predicted
- •Any major chronic illness including but not limited to Chronic Obstructive Pulmonary Disease (COPD), uncontrolled hypertension, coronary artery disease, bronchiectasis, congestive heart failure, stroke, cystic fibrosis, insulin-dependent diabetes mellitus, renal failure, liver disorders, immunodeficiency state, or other condition that would interfere with participation in the study
- •Current or > 10 pack a year pack-year tobacco use
- •Any investigational study within previous 1 month
- •Inability to perform baseline measurements
- •Inability to contact by telephone
- •Pregnancy at screening and failure to use double barrier pregnancy protection in woman of childbearing age
- •Hypersensitivity reaction to omalizumab in the past
- •Exceeds limits of dosing table (IgE <30 or 700 IU/ml) or body weight of <30 or > 150kg
- •Systemic corticosteroids within the previous month
- •Known malignant neoplasm
研究组 & 干预措施
Omalizumab
干预措施: Omalizumab (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma
时间窗: 16 Weeks of Treatment of omalizumab or placebo
Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
时间窗: 16 Weeks of Treatment of omalizumab or placebo
Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Two Group T-test in Moderate Persistent Asthma
时间窗: 16 Weeks of Treatment of omalizumab or placebo
Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
时间窗: 16 Weeks of Treatment of omalizumab or placebo
次要结局
- Change in Score on Asthma Control Test(16 Weeks of Treatment of omalizumab or placebo)
- Change in Lung Function Measure by Spirometry Test(16 Weeks of Treatment of omalizumab or placebo)
- The Effect of Omalizumab on Changes sHBEC Targets (Gene Expression Array) Compared Using Two-group T-test if Data(16 Weeks of Treatment of omalizumab or placebo)
- Change in Measures of Small Airway Dysfunction Using Impulse Oscillometry(16 Weeks of Treatment of omalizumab or placebo)