Clinical trial NCT05036733: Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma
Official title: Effects of IL-4R-alpha Inhibition (Dupixent) Inhibition On The Respiratory Microbiome And Immunologic Correlates In Patients With Severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Inhaled corticosteroids
Dupilumab
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2021-09-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Changes in Alpha-diversity of Respiratory Microbiota
timeFrame: Baseline (before dupilumab), 1 month
measure: Changes in Alpha-diversity of Respiratory Microbiota
timeFrame: Baseline (before dupilumab), 4 month
measure: Changes in Alpha-diversity of Respiratory Microbiota
timeFrame: 1 month, 4 months
measure: Change in Beta-diversity of Respiratory Microbiota
timeFrame: Baseline (before dupilumab), 1 month
measure: Change in Beta-diversity of Respiratory Microbiota
timeFrame: Baseline (before dupilumab), 4 month
measure: Change in Beta-diversity of Respiratory Microbiota
timeFrame: 1 month, 4 months
measure: Change in Relative Abundances of Microbiota Members
timeFrame: Baseline (before dupilumab), 1 month
measure: Change in Relative Abundances of Microbiota Members
timeFrame: Baseline (before dupilumab), 4 month
measure: Change in Relative Abundances of Microbiota Members
timeFrame: 1 month, 4 months
measure: Change in Respiratory Bacterial Burden
timeFrame: Baseline (before dupilumab), 1 month
measure: Change in Respiratory Bacterial Burden
timeFrame: Baseline (before dupilumab), 4 month
measure: Change in Respiratory Bacterial Burden
timeFrame: 1 month, 4 months
measure: Changes in Alpha-diversity of Stool Microbiota
timeFrame: Baseline (before dupilumab), 1 month
measure: Changes in Alpha-diversity of Stool Microbiota
timeFrame: Baseline (before dupilumab), 4 month
measure: Changes in Alpha-diversity of Stool Microbiota
timeFrame: 1 month, 4 months
measure: Change in Beta-diversity of Stool Microbiota
timeFrame: Baseline (before dupilumab), 1 month
measure: Change in Beta-diversity of Stool Microbiota
timeFrame: Baseline (before dupilumab), 4 month
measure: Change in Beta-diversity of Stool Microbiota
timeFrame: 1 month, 4 months
Secondary outcomes:
measure: Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio
timeFrame: Baseline, 1 month, 4 months
measure: Forced Expiratory Volume (FEV1)
timeFrame: Baseline, 1 month, 4 months
measure: Change in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: Baseline, 1 month, 4 months
measure: Asthma Control Test (ACT)
timeFrame: Baseline, 1 month, 4 months
measure: Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
timeFrame: Baseline, 1 month, 4 months
measure: Sino-nasal Outcome Test (SNOT-22)
timeFrame: Baseline, 1 month, 4 months
measure: Change in Prescribed Maintenance Corticosteroid Use (Inhaled or Oral), Between Baseline and 4 Months.
timeFrame: Baseline, 4 months
measure: Number of Asthma Exacerbations Requiring at Least 3 Days of Oral Corticosteroids
timeFrame: up to 4 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Yvonne Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: