Azithromycin Treatment for the Airway Microbiome in Asthma

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 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 :	February 1, 2019
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	February 2020

Arms and Interventions

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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 Name: Zithromax

Outcome Measures

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Primary Outcome Measures :

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

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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
2. Albuterol response > 12% on FEV1 after 4 puffs of albuterol
3. Ability to use combination ICS + LABA
4. 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

5. Prednisone or other oral steroids within past 3 months 3. Pregnancy or lactation 4. Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema) 5. Pre-existing liver disease (AST or ALT >10% above the upper limit of normal) 6. Smoking within the last 6 months 7. Exacerbation of asthma in past 3 months 8. Affected by a hearing disorder 9. Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator 10. 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

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Contacts

Contact: Steve White, MD	773-702-2004	swhite@medicine.bsd.uchicago.edu
Contact: Spring Maleckar	773-834-4053	smalecka@medicine.bsd.uchicago.edu

Locations

United States, Illinois
Northwestern University	Active, not recruiting
Chicago, Illinois, United States, 60201
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: Steve White, MD

Sponsors and Collaborators

University of Chicago

Northwestern University

Investigators

Principal Investigator:	Steve White, MD	University of Chicago

More Information

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Responsible Party:	University of Chicago
ClinicalTrials.gov Identifier:	NCT03736629 History of Changes
Other Study ID Numbers:	IRB17-1287
First Posted:	November 9, 2018
Last Update Posted:	February 8, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	We will share individual participant data that is de-identified available to all qualified investigators
Supporting Materials:	Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)
Time Frame:	Upon publication of the major manuscript to be generated from this study. Data will be deposited in an appropriate major database (e.g., sequencing information will be deposited in a genetics bio-bank).
Access Criteria:	All qualified investigators who sign appropriate data use agreements and material transfer agreements with the University of Chicago and Northwestern University

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