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

October 2, 2024 updated by: Yvonne J Huang, University of Michigan

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dupilumab
Drug: Dupilumab

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months
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.
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months
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.
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months
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.
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months
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.
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months
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..
Baseline (before dupilumab), 1 month
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.
Baseline (before dupilumab), 4 month
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.
1 month, 4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, 1 month, 4 months
Forced Expiratory Volume (FEV1)
Time Frame: Baseline, 1 month, 4 months
FEV1 measure reported as a percentage of predicted FEV1.
Baseline, 1 month, 4 months
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.
Baseline, 1 month, 4 months
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.
Baseline, 1 month, 4 months
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.
Baseline, 1 month, 4 months
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.
Baseline, 1 month, 4 months
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.
Baseline, 4 months
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.
up to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Regeneron Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yvonne Huang, MD, University of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 22, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 29, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HUM00196809

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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