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Azithromycin Treatment for the Airway Microbiome in Asthma

Primary Purpose

Asthma Chronic

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Azithromycin

Placebo

About this trial

This is an interventional treatment trial for Asthma Chronic focused on measuring Asthma, Azithromycin, Microbiome, Sputum

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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:
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
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

Sites / Locations

Northwestern University
University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

No Intervention

Arm Label

Placebo

Azithromycin

Non-asthmatic controls

Arm Description

8 weeks of placebo capsule once daily by mouth

8 weeks of Azithromycin (250 mg) capsule once daily by mouth

Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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

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).

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

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

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

Full Information

NCT ID

NCT03736629

First Posted

November 7, 2018

Last Updated

August 3, 2023

Sponsor

University of Chicago

Collaborators

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT03736629

Brief Title

Azithromycin Treatment for the Airway Microbiome in Asthma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Terminated

Why Stopped

Inability to accrue patients, particularly after COVID pandemic.

Study Start Date

February 1, 2019 (Actual)

Primary Completion Date

March 1, 2021 (Actual)

Study Completion Date

June 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

Collaborators

Northwestern University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma Chronic

Keywords

Asthma, Azithromycin, Microbiome, Sputum

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

8 weeks of placebo capsule once daily by mouth

Arm Title

Azithromycin

Arm Type

Active Comparator

Arm Description

8 weeks of Azithromycin (250 mg) capsule once daily by mouth

Arm Title

Non-asthmatic controls

Arm Type

No Intervention

Arm Description

Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given.

Intervention Type

Drug

Intervention Name(s)

Azithromycin

Other Intervention Name(s)

Zithromax

Intervention Description

8 weeks of Azithromycin (250 mg) once daily by mouth

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks

Description

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

Time Frame

Baseline and 8 weeks

Secondary Outcome Measure Information:

Title

Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks

Description

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

Title

Sputum Eosinophils Change From Baseline Over 8 Weeks

Description

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

Title

Sputum Neutrophils Change From Baseline Over 8 Weeks

Description

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

Title

Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks

Description

Time Frame

8 weeks

Title

Microbiome Shannon Alpha-diversity Score Change From Baseline to 8 Weeks

Description

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

Title

Microbiome Beta-diversity Score Change From Baseline to 8 Weeks

Description

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

Title

Microbiome Change in Relative Proportion of Top 10 Genera From Baseline to 8 Weeks

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steve White, MD

Organizational Affiliation

University of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60201

Country

United States

Facility Name

University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

We will share individual participant data that is de-identified available to all qualified investigators

IPD Sharing 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).

IPD Sharing Access Criteria

All qualified investigators who sign appropriate data use agreements and material transfer agreements with the University of Chicago and Northwestern University

Citations:

PubMed Identifier

33032168

Citation

Vogelmeier CF, Fuhlbrigge A, Jauhiainen A, Scheepers LEJM, Bengtsson T, Peterson S, Karlsson N, Sethi T, Locantore N, Tal-Singer R, Rennard S, Fageras M, Da Silva CA. COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development. Respir Med. 2020 Nov;173:106175. doi: 10.1016/j.rmed.2020.106175. Epub 2020 Sep 28.

Results Reference

result

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Azithromycin Treatment for the Airway Microbiome in Asthma

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