Effects of IL-4R-alpha Inhibition (Dupixent) Inhibition On The Respiratory Microbiome And Immunologic Correlates In Patients With Severe Asthma
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Changes in Alpha-diversity of Respiratory Microbiota
研究概览
简要总结
The overall goal of this study is to understand biological responses related to dupilumab treatment among severe asthma patients.
Not all asthma is the same, and characteristics of asthma vary from person to person. The study will investigate whether the study drug can help to improve the health of participants lungs, boost immune response, as well as improve quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Physician-diagnosed/managed severe asthma patients that are clinically eligible for dupilumab
- •Current treatment with a medium-to-high-dose inhaled glucocorticoid (fluticasone propionate at a total daily dose of greater or equal (≥) 440 μg or equipotent equivalent) plus up to at least one additional controller (e.g., a long-acting β2-agonist or leukotriene receptor antagonist)
- •Eosinophilic asthma phenotype (blood eosinophil level >300) or asthma requiring daily oral corticosteroids
- •Asthma that is uncontrolled, as defined by a score on the Asthma Control Test of 19 or lower, or a worsening of asthma in the past year that led to an asthma hospitalization, Emergency Department visit, or 3 days of oral corticosteroids
- •Severity of asthma that, in the opinion of the subject's asthma care specialist, requires dupilumab for control
- •For women of childbearing age: agree to use birth control or remain abstinent during the duration of the study.
排除标准
- •Patients with diagnosis of other chronic lung diseases (e.g. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, Churg-Strauss syndrome, Allergic bronchopulmonary aspergillosis, etc.)
- •Current smoker or reported smoking within 1 month of the screening visit (tobacco or any inhaled recreational product)
- •Greater than 10 total pack-year of cigarette smoking history
- •Treatment with oral corticosteroids for an asthma exacerbation 1 month prior to screening or during the screening period
- •Use of any biologic therapy for asthma within the past 3 months
- •Respiratory or Gastrointestinal illness within 1 month prior to screening or during the screening period
- •Treatment with antibiotics for acute infections within six weeks prior to screening or during the screening period.
- •Pregnancy at enrollment or during the study
- •Known hypersensitivity to dupilumab or its excipients
研究组 & 干预措施
Dupilumab
干预措施: Dupilumab (Drug)
结局指标
主要结局
Changes in Alpha-diversity of Respiratory Microbiota
时间窗: 1 month, 4 months
α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' calculated diversity and then finding the difference between time points. A higher Shannon Diversity Index value indicates higher diversity. A value of zero indicates the presence of only one kind of species of bacteria.
Change in Beta-diversity of Respiratory Microbiota
时间窗: 1 month, 4 months
Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' distance between time points. Bray-Curtis dissimilarity ranges from 0 to 1. A higher Bray-Curtis Distance indicates a greater difference in diversity between time points.
Change in Relative Abundances of Microbiota Members
时间窗: 1 month, 4 months
Relative abundance was calculated by finding the proportion of a classified species out of all bacterial classifications in an induced sputum sample. Relative abundance was calculated after 1 month and after 4 months on dupilumab. The change in relative abundance of each species across all available samples was calculated by taking the difference between time points.
Change in Respiratory Bacterial Burden
时间窗: 1 month, 4 months
Bacterial Burden was estimated by scaling the species relative abundance to a known cell count of I. Halotolerans that was spiked into an induced sputum sample before extraction for sequencing. Bacterial burden was calculated at after 1 month and after 4 months on dupilumab. The change in bacterial burden was calculated by aggregating all burden values per participant and taking the difference between time points.
Changes in Alpha-diversity of Stool Microbiota
时间窗: 1 month, 4 months
α-diversity was calculated using the Shannon Diversity Index at the species level from stool samples. Shannon's Diversity Index values were obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' calculated diversity and then finding the difference between time points. A higher Shannon Diversity Index value indicates higher diversity. A value of zero indicates the presence of only one kind of species of bacteria.
Change in Beta-diversity of Stool Microbiota
时间窗: 1 month, 4 months
Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool samples obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' distance between time points. Bray-Curtis dissimilarity ranges from 0 to 1. A higher Bray-Curtis Distance indicates a greater difference in diversity between time points.
次要结局
- Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio(Baseline, 1 month, 4 months)
- Forced Expiratory Volume (FEV1)(Baseline, 1 month, 4 months)
- Change in Fractional Exhaled Nitric Oxide (FeNO)(Baseline, 1 month, 4 months)
- Asthma Control Test (ACT)(Baseline, 1 month, 4 months)
- Mini Asthma Quality of Life Questionnaire Score (mAQLQ)(Baseline, 1 month, 4 months)
- Sino-nasal Outcome Test (SNOT-22)(Baseline, 1 month, 4 months)
- Change in Prescribed Maintenance Corticosteroid Use (Inhaled or Oral), Between Baseline and 4 Months.(Baseline, 4 months)
- Number of Asthma Exacerbations Requiring at Least 3 Days of Oral Corticosteroids(up to 4 months)
研究者
Yvonne J Huang
Associate Professor of Internal Medicine and Microbiology/Immunology
University of Michigan