Azithromycin Treatment for the Airway Microbiome in Asthma

• Sponsor: University of Chicago (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03736629
• Collaborator: Northwestern University (Other)
• Enrollment: 16
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 40
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma Chronic	Drug: Azithromycin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The AZITRAMBA Trial: Azithromycin Treatment for the Airway Microbiome in Asthma
• Actual Study Start Date: Feb 1, 2019
• Actual Primary Completion Date: Mar 1, 2021
• Anticipated Study Completion Date: Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 8 weeks of placebo capsule once daily by mouth	Drug: Placebo; Placebo
Active Comparator: Azithromycin 8 weeks of Azithromycin (250 mg) capsule once daily by mouth	Drug: Azithromycin; 8 weeks of Azithromycin (250 mg) once daily by mouth; Other Names: Zithromax

Outcome Measures

Primary Outcome Measures

1. Asthma Control Test (ACT) score change from baseline over 8 weeks [8 weeks]

   Score ranging from 0 to 40 indicating the degree of asthma symptoms. Lower score indicating worse asthma symptoms.

Secondary Outcome Measures

1. Forced expiratory volume (FEV1) change from baseline over 8 weeks [8 weeks]

   Volume of air exhaled in 1 second on a forced expiration, indicating the degree of airflow obstruction in asthma

2. Sputum eosinophils change from baseline over 8 weeks [8 weeks]

   Proportion of 'eosinophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation

3. Sputum neutrophils change from baseline over 8 weeks [8 weeks]

   Proportion of 'neutrophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation

4. COMPEX score of asthma severity from baseline over 8 weeks [8 weeks]

   A weighted scoring system that describes asthma symptoms done on a daily basis

5. 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

6. 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

7. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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:

3. Current use of medications that prolong QTc interval

4. Current use of omalizumab or other ant-IgE therapies

5. Current use of anti-IL 5 therapies

6. Current use of anticoagulants

7. Prednsione or other oral steroids within past 3 months

8. Pregnancy or lactation, or plans to become pregnant

9. Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema)

10. Pre-existing liver disease by history

11. Smoking within the last 6 months

12. Exacerbation of asthma in past 3 months

13. Affected by a hearing disorder

14. Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator

15. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60201
2	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• Northwestern University

Investigators

• Principal Investigator: Steve White, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT03736629
• Other Study ID Numbers: IRB17-1287
• First Posted: Nov 9, 2018
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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.: Yes
• Keywords provided by University of Chicago: Asthma; Azithromycin; Microbiome; Sputum
• Additional relevant MeSH terms: Asthma; Azithromycin

Study Results

No Results Posted as of Nov 1, 2021