Skip to main content
OpenTrials
Completed

NCT Number: NCT05036733

Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dupilumab

Drug

Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.

Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.

Other names: Dupixent

Primary outcomes

  1. Changes in Alpha-diversity of Respiratory Microbiota

    Time frame: Baseline (before dupilumab), 1 month

    α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained at Baseline and after 1 month 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.

  2. Changes in Alpha-diversity of Respiratory Microbiota

    Time frame: Baseline (before dupilumab), 4 month

    α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained at baseline 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.

  3. Changes in Alpha-diversity of Respiratory Microbiota

    Time frame: 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.

  4. Change in Beta-diversity of Respiratory Microbiota

    Time frame: Baseline (before dupilumab), 1 month

    Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained at baseline and after 1 month 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, which is unitless, indicates a greater difference in diversity between the time points.

  5. Change in Beta-diversity of Respiratory Microbiota

    Time frame: Baseline (before dupilumab), 4 month

    Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained at baseline 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.

  6. Change in Beta-diversity of Respiratory Microbiota

    Time frame: 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.

  7. Change in Relative Abundances of Microbiota Members

    Time frame: Baseline (before dupilumab), 1 month

    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 at baseline and after 1 month on dupilumab. The change in relative abundance of each species across all available samples was calculated by taking the difference between time points.

  8. Change in Relative Abundances of Microbiota Members

    Time frame: Baseline (before dupilumab), 4 month

    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 at baseline 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.

  9. Change in Relative Abundances of Microbiota Members

    Time frame: 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.

  10. Change in Respiratory Bacterial Burden

    Time frame: Baseline (before dupilumab), 1 month

    Bacterial burden was estimated by scaling species relative abundances to a known cell count of Imtechella halotolerans (Zymo) that was spiked into an induced sputum sample before extraction for sequencing. Bacterial burden was calculated at baseline and after 1 month on dupilumab. The change in bacterial burden was calculated by aggregating all burden values per participant and taking the difference between time points.

  11. Change in Respiratory Bacterial Burden

    Time frame: Baseline (before dupilumab), 4 month

    Bacterial burden was estimated by scaling all species relative abundances to a known cell count of Imtechella halotolerans that was spiked into sputum samples before extraction for sequencing. Bacterial burden was calculated at baseline 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.

  12. Change in Respiratory Bacterial Burden

    Time frame: 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.

  13. Changes in Alpha-diversity of Stool Microbiota

    Time frame: Baseline (before dupilumab), 1 month

    α-diversity was calculated using the Shannon diversity index at the species level from stool samples obtained at baseline and after 1 month 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.

  14. Changes in Alpha-diversity of Stool Microbiota

    Time frame: Baseline (before dupilumab), 4 month

    α-diversity was calculated using the Shannon diversity Index at the species level from stool samples obtained at baseline 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.

  15. Changes in Alpha-diversity of Stool Microbiota

    Time frame: 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.

  16. Change in Beta-diversity of Stool Microbiota

    Time frame: Baseline (before dupilumab), 1 month

    Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool samples. Samples were obtained baseline and after 1 month on dupilumab and the Bray-Curtis Distance calculated. 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..

  17. Change in Beta-diversity of Stool Microbiota

    Time frame: Baseline (before dupilumab), 4 month

    Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool samples obtained at baseline 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.

  18. Change in Beta-diversity of Stool Microbiota

    Time frame: 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.

Secondary outcomes

  1. Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio

    Time frame: Baseline, 1 month, 4 months

    Ratio of the volume of air exhaled in 1 sec (FEV1) divided by the total volume exhaled (FVC). FEV1/FVC < 0.70 (or less than lower limit of age-predicted normal) is clinically diagnostic of obstructive lung disease.

  2. Forced Expiratory Volume (FEV1)

    Time frame: Baseline, 1 month, 4 months

    FEV1 measure reported as a percentage of predicted FEV1.

  3. Change in Fractional Exhaled Nitric Oxide (FeNO)

    Time frame: Baseline, 1 month, 4 months

    Fractional exhaled nitric oxide is a clinical biomarker for type 2 airway inflammation. FeNO >25 is considered indicative of type 2 airway inflammation.

  4. Asthma Control Test (ACT)

    Time frame: Baseline, 1 month, 4 months

    The Asthma Control Test is a clinically validated questionnaire that assesses level of asthma control based on a 4-week recall of symptoms and daily functioning captured in 5 items. Each item is scored on a 5-point scale, and the total score is the sum of the values for all 5 items (range 5-25). A score of 5 represents worst-controlled asthma and 25 represents best-controlled asthma. An ACT score >19 indicates well-controlled asthma; the minimal clinically important difference in score is 3.

  5. Mini Asthma Quality of Life Questionnaire Score (mAQLQ)

    Time frame: Baseline, 1 month, 4 months

    The mini-Asthma Quality of Life Questionnaire (mAQLQ) consists of 15 questions covering 4 domains: symptoms (5 questions), activity limitations (4 questions), emotional function (3 questions), and environmental stimuli (3 questions). The recall time for the mAQLQ is 2 weeks and each item is scored on a 7-point scale. Total scores per participant are the average of the 15 items and range from 1-7, with higher scores indicative of better quality of life. The minimum clinically important difference is 0.5.

  6. Sino-nasal Outcome Test (SNOT-22)

    Time frame: Baseline, 1 month, 4 months

    This is a 22 item questionnaire. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The score ranges between 0 and 110. A higher score means worse outcome.

  7. Change in Prescribed Maintenance Corticosteroid Use (Inhaled or Oral), Between Baseline and 4 Months.

    Time frame: Baseline, 4 months

    Count of participants whose maintenance corticosteroid prescription changed between baseline and 4 months.

  8. Number of Asthma Exacerbations Requiring at Least 3 Days of Oral Corticosteroids

    Time frame: up to 4 months

    Number of asthma exacerbations requiring at least 3 days of oral corticosteroids across the entire study population over the course of the study.

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

Effects of IL-4R-alpha Inhibition (Dupixent) Inhibition On The Respiratory Microbiome And Immunologic Correlates In Patients With Severe Asthma

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Sep 8, 2021
Registry last updated
Oct 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.