Azithromycin Treatment for the Airway Microbiome in Asthma

Study Overview
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Brief Summary
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The purpose of this study to determine whether the bacteria inside the lungs of people with asthma can be modified (changed) if they are given an antibiotic and if this change is associated with an improvement in asthma symptoms.

Official Title
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The AZITRAMBA Trial: Azithromycin Treatment for the Airway Microbiome in Asthma

Conditions
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Asthma Chronic

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (All participants): Age 18 - 55 years Able to provide informed consent Smoking history < 10 pack-years Inclusion Criteria for subjects with poorly controlled asthma Methacholine PC20 < 16 mg/ml or PD 20 < 400 mcg/ml or albuterol response > 12% on FEV1 after 4 puffs of albuterol Currently prescribed ICS + LABA Meet definition for Th2-low asthma: peripheral blood eosinophil count < 300 and exhaled nitric oxide level < 30 ppb. Exclusion Criteria (All participants) History of allergy or intolerance to any medications used in this study Medication exclusions: Current use of medications that prolong QTc interval Current use of omalizumab or other ant-IgE therapies Current use of anti-IL 5 therapies Current use of anticoagulants Prednsione or other oral steroids within past 3 months Pregnancy or lactation, or plans to become pregnant Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema) Pre-existing liver disease by history Smoking within the last 6 months Exacerbation of asthma in past 3 months Affected by a hearing disorder Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator Corrected QT interval > 450 msec. Patients with known cardiac history or prolonged QT interval on a screening EKG are excluded given the small but real potential for macrolide-related side effects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>8 weeks of placebo capsule once daily by mouth | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Azithromycin<br>8 weeks of Azithromycin (250 mg) capsule once daily by mouth | Drug: Azithromycin<br>* 8 weeks of Azithromycin (250 mg) once daily by mouth<br>* Other names: Zithromax;|
| No Intervention: Non-asthmatic controls<br>Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks | Score ranging from 0 to 40 indicating the degree of asthma symptoms. Lower score indicating worse asthma symptoms. | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks | Volume of air exhaled in 1 second on a forced expiration, expressed as percent of predicted, indicating the degree of airflow obstruction in asthma | 8 weeks | 
| Sputum Eosinophils Change From Baseline Over 8 Weeks | Percentage of 'eosinophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation | Baseline and 8 weeks | 
| Sputum Neutrophils Change From Baseline Over 8 Weeks | Percentage of 'neutrophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation | Baseline and 8 weeks | 
| Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks | The outcome is derived from a weighted scoring system called CompEx that describes asthma symptoms recorded on a daily basis. Final result is a dichotomous outcome indicating whether the patient had a diary event based on changes in peak expiratory flow, reliever use, and asthma symptoms or a serious exacerbation (deterioration of asthma leading to oral corticosteroid use, emergency room admission, or hospital admission). | 8 weeks | 
| Microbiome Shannon Alpha-diversity Score Change From Baseline to 8 Weeks | A measure of the diversity of the bacteria in the sputum or oral sample; that is, how many different types of bacteria are present. This value decreases in severe asthma | 8 weeks | 
| Microbiome Beta-diversity Score Change From Baseline to 8 Weeks | A second measure of the diversity of the bacteria in the sputum or oral sample; that is, how many different types of bacteria are present. This value decreases in severe asthma | 8 weeks | 
| Microbiome Change in Relative Proportion of Top 10 Genera From Baseline to 8 Weeks | A measure of how many of the top types of bacteria are present in the sputum or oral sample. Value changes with asthma | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Azithromycin, Microbiome, Sputum