Asthma Chronic
Conditions
Keywords
Asthma, Azithromycin, Microbiome, Sputum
Brief summary
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.
Interventions
DRUGAzithromycin
8 weeks of Azithromycin (250 mg) once daily by mouth
DRUGPlacebo
Placebo
Sponsors
Northwestern University
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
(All participants): 1. Age 18 - 55 years 2. Able to provide informed consent 3. Smoking history \< 10 pack-years Inclusion Criteria for subjects with poorly controlled asthma 1. Methacholine PC20 \< 16 mg/ml or PD 20 \< 400 mcg/ml or albuterol response \> 12% on FEV1 after 4 puffs of albuterol 2. Currently prescribed ICS + LABA 3. Meet definition for Th2-low asthma: peripheral blood eosinophil count \< 300 and exhaled nitric oxide level \< 30 ppb.
Exclusion criteria
(All participants) 1. History of allergy or intolerance to any medications used in this study 2. Medication exclusions: 1. Current use of medications that prolong QTc interval 2. Current use of omalizumab or other ant-IgE therapies 3. Current use of anti-IL 5 therapies 4. Current use of anticoagulants 3. Prednsione or other oral steroids within past 3 months 4. Pregnancy or lactation, or plans to become pregnant 5. Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema) 6. Pre-existing liver disease by history 7. Smoking within the last 6 months 8. Exacerbation of asthma in past 3 months 9. Affected by a hearing disorder 10. Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator 11. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks | Baseline and 8 weeks | Score ranging from 0 to 40 indicating the degree of asthma symptoms. Lower score indicating worse asthma symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks | 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 |
| Sputum Eosinophils Change From Baseline Over 8 Weeks | Baseline and 8 weeks | Percentage of 'eosinophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation |
| Sputum Neutrophils Change From Baseline Over 8 Weeks | Baseline and 8 weeks | Percentage of 'neutrophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation |
| Microbiome Change in Relative Proportion of Top 10 Genera From Baseline to 8 Weeks | 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 |
| Microbiome Shannon Alpha-diversity Score Change From Baseline to 8 Weeks | 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 |
| Microbiome Beta-diversity Score Change From Baseline to 8 Weeks | 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 |
| Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 8 weeks of placebo capsule once daily by mouth
Placebo: Placebo | 3 |
| Azithromycin 8 weeks of Azithromycin (250 mg) capsule once daily by mouth
Azithromycin: 8 weeks of Azithromycin (250 mg) once daily by mouth | 2 |
| Non-asthmatic Controls Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given. | 12 |
| Total | 17 |
Baseline characteristics
| Characteristic | Placebo | Total | Non-asthmatic Controls | Azithromycin |
|---|---|---|---|---|
| Age, Continuous | 50.5 years | 39.5 years | 35.5 years | 47.4 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 4 Participants | 4 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 17 participants | 12 participants | 2 participants |
| Sex: Female, Male Female | 3 Participants | 14 Participants | 9 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
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.
Time frame: Baseline and 8 weeks
Population: Outcome variable is not applicable to non-asthmatic controls, as they were not assessed for asthma symptoms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks | 0.67 score on a scale | Standard Error 0.67 |
| Azithromycin | Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks | 0.00 score on a scale | Standard Error 2 |
Comparison: Study did not reach its accrual goal. Sample size is too small to draw any conclusions.p-value: 0.7295% CI: [-6.14, 4.81]t-test, 2 sided
Secondary
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
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks | 1.67 percentage of predicted | Standard Error 3.76 |
| Azithromycin | Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks | -4.00 percentage of predicted | Standard Error 11 |
| Non-asthmatic Controls | Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks | -2.92 percentage of predicted | Standard Error 1.37 |
p-value: 0.5995% CI: [-35.98, 24.65]t-test, 2 sided
Secondary
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
Time frame: 8 weeks
Population: Insufficient sample size for meaningful results in intervention arms. Microbiome assays were not performed.
Secondary
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
Time frame: 8 weeks
Population: Insufficient sample size for meaningful results in intervention arms. Microbiome assays were not performed.
Secondary
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
Time frame: 8 weeks
Population: Insufficient sample size for meaningful results in intervention arms due to low accrual. Microbiome assays were not performed.
Secondary
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).
Time frame: 8 weeks
Population: Outcome measure is not applicable to non-asthmatic controls, as they were not assessed for asthma severity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks | 1 Participants |
| Azithromycin | Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks | 0 Participants |
Comparison: Study did not reach its accrual goal. Sample size is too small to draw any conclusions.p-value: 1Fisher Exact
Secondary
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
Time frame: Baseline and 8 weeks
Population: Some patients had missing data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Sputum Eosinophils Change From Baseline Over 8 Weeks | 0.00 percentage of eosinophils |
| Azithromycin | Sputum Eosinophils Change From Baseline Over 8 Weeks | 0.00 percentage of eosinophils |
| Non-asthmatic Controls | Sputum Eosinophils Change From Baseline Over 8 Weeks | 0.06 percentage of eosinophils |
Secondary
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
Time frame: Baseline and 8 weeks
Population: Some patients had missing data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Sputum Neutrophils Change From Baseline Over 8 Weeks | -0.00 percentage of neutrophils |
| Azithromycin | Sputum Neutrophils Change From Baseline Over 8 Weeks | 1.59 percentage of neutrophils |
| Non-asthmatic Controls | Sputum Neutrophils Change From Baseline Over 8 Weeks | -10.03 percentage of neutrophils |