CompletedNCT01537133Updated Nov 30, 2016Results posted

Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment

An interventional study of fluticasone and Placebo in Asthma and Atopy, sponsored by Milton S. Hershey Medical Center. Completed at 9 sites in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-11-30.

Sponsored by Milton S. Hershey Medical Center · Not applicable and Interventional

Phase: Not applicable
Study type: Interventional
Enrollment: 84
Allocation: Randomized
Ages: 18 Years to 60 Years
Sex: All

Study summary

There are new, very sensitive methods for detecting bacteria. These methods show that hundreds of millions of microbes (organisms that can only be seen with microscopes), especially bacteria, live in healthy people. The collection of different microbes found in a site is called a "microbiome." The investigators know that microbiomes of the skin, sinuses, mouth, gastro-intestinal tract, etc. differ from each other. The make-up of the microbiome - which bacteria are found in a site - may be necessary for good health. For example, the microbiome of the mouth is different in people with inflammation of the gums (periodontitis), and the microbiome of the bowel is different in people with inflammation of the intestinal tract (inflammatory bowel disease).

The purpose of this research study is to find out if the microbiome in the lungs is different in healthy people without asthma compared to people with asthma. This study will also find out if the microbiome of the lungs changes when people with asthma take a daily "controller" medication called an inhaled corticosteroid.

Read the detailed description

Two broad specific aims of this study are: 1)To evaluate whether the microbiota of the bronchial airways in atopic asthmatics and atopic healthy controls differ in microbial diversity, richness, evenness, or composition of specific bacterial taxa. 2) To determine whether inhaled corticosteroid treatment alters bronchial microbial community composition in asthmatics.

Conditions studied

Asthma
Atopy

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Asthma 4,012

In context

Asthma

4,012 studies on the registry are indexed under Asthma; 514 are open to participants now.

This study's enrollment of 84 is close to the median of 83 across 2,814 interventional studies indexed under Asthma.

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Lead sponsor

Milton S. Hershey Medical Center is the lead sponsor of 491 studies on the registry; 59 are open to participants now.

Of its 58 completed or terminated interventional studies of FDA-regulated products, 44 (76%) have results posted.

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Who can participate

Ages eligible: 18 Years to 60 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Asthmatic:

History of physician-diagnosed asthma.
Methacholine PC20 \< 8mg/ml and/or FEV1 improvement ≥ 12% in response to 180 mcg albuterol.
FEV1 ≥ 70% of predicted after 180 mcg albuterol.
Stable asthma for ≥ 3 months prior to enrollment (no urgent care visits, no systemic corticosteroid treatment).
Asthma Control Questionnaire 6 Score \< 1.5.
Able to provide informed consent.
Able to perform spirometry as per ATS criteria.
Evidence by allergen skin test of sensitivity to an aeroallergen.
Willingness, if female and able to conceive, to utilize one medically-acceptable form of contraception.

Healthy Control:

Evidence by allergen skin test of sensitivity to an aeroallergen.
Able to provide informed consent.
Able to perform spirometry as per ATS criteria.

Exclusion criteria

Exclusion Criteria:

Asthmatic:

Presence of lung disease other than asthma.
Use of > 10 doses of nasal corticosteroids in the previous 3 months.
Presence of significant medical illness or other chronic diseases whose treatment could affect the clinical features measured, responses to the therapies to be given in this study, or risks of participating in the study.
History of atrial or ventricular tachyarrhythmia.
Changes suggestive of cardiac ischemia on ECG at baseline.
History of upper respiratory infection, sinusitis, bronchitis, or antibiotic use in the previous 3 months.
History of chronic sinus disease.
Smoking > 5 pack-years, or within the past year
History of long-term controller medication use for asthma (inhaled or oral corticosteroid, leukotriene pathway antagonist, cromolyn, or theophylline within the preceding 6 months.
History of bleeding disorder.
Reduced creatinine clearance.
Inability, in the opinion of the Study Investigator, to coordinate use of inhaler or otherwise comply with medication regimens.
Contraindication to bronchoscopy on history or examination.

Healthy Control:

History of chronic respiratory disease including asthma.
Presence of significant medical illness or other chronic diseases whose treatment could affect the clinical features measured, responses to the therapies to be given in this study, or risks of participating in the study.
History of atrial or ventricular tachyarrhythmia.
Changes suggestive of cardiac ischemia on ECG at baseline.
History of upper respiratory infection, sinusitis, bronchitis, or antibiotic use in the previous 3 months.
Methacholine PC20 \< 16 mg/ml or FEV1 improvement ≥ 12% in response to albuterol.
History of chronic sinus disease
Smoking > 5 pack-years, or within the past year
Use of > 10 doses of a nasal corticosteroid preparation in the previous 3 months
FEV1 or FVC \< 80% predicted.
History of bleeding disorder.
Reduced creatinine clearance.
Contraindication to bronchoscopy on history or examination.

Study design

Phase: Not applicable
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 84 participants (actual)

Study arms

Experimental
Inhaled corticosteroid
Fluticasone (250 mcg/puff, one puff, twice a day)
Drug: fluticasone
Placebo comparator
Placebo
Placebo fluticasone (one puff, twice a day)
Drug: Placebo
No intervention
Healthy Control
No intervention
Atopic Non-asthmatics

Interventions

Drugfluticasone
Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day
Also known as: Flovent 250
DrugPlacebo
Dry Powder Inhaler: Placebo

What researchers measure

Primary outcomes

Microbial Community Richness
Richness is the total number of different bacterial taxa detected in the sample.
Time frame: baseline and after 6 weeks of treatment
Microbial Community Diversity
The Shannon diversity index is a type of entropy measure and is a function of the distribution of the total number of organisms across all of the species. If S is the total number of species in the sample and p\_i is the number of organisms in the i-th species divided by the total number of organisms, then Diversity = -Σ p\_i log(p\_i).
Time frame: baseline and after 6 weeks of treatment
Microbial Community Evenness
Pielou's evenness index is a scaled measure of biodiversity and is equal to the observed Shannon diversity index divided by the maximum possible Shannon diversity index, which would occur if all of the species in the sample were equally abundant. Evenness = D/log(S), where D is the Shannon Diversity index and log(S) is the maximum diversity of the sample.
Time frame: baseline and after 6 weeks of treatment

Results

Posted Nov 30, 2016

Participant flow

Participant flow — Overall Study
Milestone	Inhaled Corticosteroid	Placebo	Healthy Control	Atopic Non-asthmatics
Started	28	14	21	21
Completed	25	14	21	21
Not completed	3	0	0	0
Withdrew: Withdrawal by subject	2	0	0	0
Withdrew: Lost to follow-up	1	0	0	0

Outcome measures

PrimaryMicrobial Community Richness

Richness is the total number of different bacterial taxa detected in the sample.

Time frame:: baseline and after 6 weeks of treatment
Reported as:: Median · number of bacterial taxa

Microbial Community Richness
number of bacterial taxa	Atopic Asthmatics Treated With Inhaled Corticosteroids	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control
baseline	449 (376 to 613)	543 (484 to 684)	483 (437 to 646)	444 (400 to 530)
after 6 weeks of treatment	456 (351 to 578)	405 (385 to 714)	NA (NA to NA)	NA (NA to NA)

PrimaryMicrobial Community Diversity

The Shannon diversity index is a type of entropy measure and is a function of the distribution of the total number of organisms across all of the species. If S is the total number of species in the sample and p\_i is the number of organisms in the i-th species divided by the total number of organisms, then Diversity = -Σ p\_i log(p\_i).

Time frame:: baseline and after 6 weeks of treatment
Reported as:: Median · Shannon Diversity Index

Microbial Community Diversity
Shannon Diversity Index	Atopic Asthmatics Treated With Inhaled Corticosteroids	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control
baseline	5.4 (4.9 to 5.6)	5.7 (5.0 to 6.0)	5.6 (5.2 to 6.0)	5.3 (5.2 to 5.5)
after 6 weeks of treatment	5.0 (4.6 to 5.7)	5.1 (4.8 to 5.7)	NA (NA to NA)	NA (NA to NA)

PrimaryMicrobial Community Evenness

Pielou's evenness index is a scaled measure of biodiversity and is equal to the observed Shannon diversity index divided by the maximum possible Shannon diversity index, which would occur if all of the species in the sample were equally abundant. Evenness = D/log(S), where D is the Shannon Diversity index and log(S) is the maximum diversity of the sample.

Time frame:: baseline and after 6 weeks of treatment
Reported as:: Median · Pielou's evenness index

Microbial Community Evenness
Pielou's evenness index	Atopic Asthmatics Treated With Inhaled Corticosteroids	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control
baseline	0.88 (0.81 to 0.90)	0.88 (0.79 to 0.91)	0.90 (0.83 to 0.94)	0.86 (0.83 to 0.91)
after 6 weeks of treatment	0.85 (0.76 to 0.90)	0.86 (0.81 to 0.88)	NA (NA to NA)	NA (NA to NA)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Inhaled Corticosteroid	—	0/28 (0%)	2/28 (7.1%)
Placebo	—	0/14 (0%)	2/14 (14.3%)

Most frequent other events

Most frequent other events
Event	Inhaled Corticosteroid	Placebo
Acute nasopharyngitisRespiratory, thoracic and mediastinal disorders	2/28	2/14

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
Median	30 (26 to 40)	37 (25 to 40)	28 (25 to 42)	28 (24 to 45)	30 (25 to 42)

Gender
Gender(Participants)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
Female	16	7	11	12	46
Male	12	7	10	9	38

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
White	16	9	11	15	51
Black	7	3	6	3	19
Hispanic or Latio	3	0	0	2	5
Other	2	2	4	1	9

Forced Expiratory Volume in 1 second
Forced Expiratory Volume in 1 second(percent of predicted)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
Median	94 (76 to 99)	84 (77 to 89)	98 (89 to 108)	100 (94 to 107)	96 (86 to 105)

Blood Eosinophils
Blood Eosinophils(percent of cells in blood sample)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
Median	3.3 (1.3 to 5.7)	3.6 (2 to 4.8)	2.0 (1.4 to 2.9)	1.4 (1.0 to 3.0)	2.0 (1.2 to 4.0)

Sputum eosinophils
Sputum eosinophils(percent of cells in sputum sample)	Atopic Asthmatics Treated With Inhaled Corticosteroid	Atopic Asthmatics Treated With Placebo	Atopic Non-asthmatics	Healthy Control	Total
Median	0.3 (0.0 to 0.8)	0.7 (0 to 1.5)	0 (0 to 0.45)	0 (0 to 0.4)	0.2 (0.0 to 0.6)

Study locations

9 sites

University of California, San Francisco, Adult
San Francisco, California 94143-0130, United States
National Jewish Health
Denver, Colorado 80206, United States
Northwestern Memorial Hospital
Chicago, Illinois 60611, United States
Brigham & Women's Hospital
Boston, Massachusetts 02115, United States
Washington University
St Louis, Missouri 63110, United States
Duke University School of Medicine
Durham, North Carolina 27110, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157, United States
University of Pittsburgh, Adult
Pittsburgh, Pennsylvania 15213, United States
University of Wisconsin
Madison, Wisconsin 53972, United States

References and documents

Publications

Durack J, Christian LS, Nariya S, Gonzalez J, Bhakta NR, Ansel KM, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Peters SP, Rosenberg SR, Sorkness CA, Wechsler ME, Wenzel SE, White SR, Lynch SV, Boushey HA, Huang YJ; National Heart, Lung, and Blood Institute's "AsthmaNet". Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma. J Allergy Clin Immunol. 2020 Nov;146(5):1016-1026. doi: 10.1016/j.jaci.2020.03.028. Epub 2020 Apr 13. PubMed 32298699 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 30, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01537133
Lead sponsor: Milton S. Hershey Medical Center
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Responsible party: dave mauger (Professor of Public Health Sciences, Milton S. Hershey Medical Center) — Principal investigator
First posted: Feb 23, 2012
Start date: Oct 2012
Primary completion: Jul 2014
Completion: Jul 2014
Results posted: Nov 30, 2016
Last update: Nov 30, 2016

Study contacts

Elliot Israel, MD

principal investigator · Brigham and Women's Hospital

Lewis Smith, MD

principal investigator · Northwestern Memorial Hospital

Richard Martin, MD

principal investigator · National Jewish Health

Mario Castro, MD

principal investigator · Washington University School of Medicine

Monica Kraft, MD

principal investigator · Duke University

Stephen Peters, MD

principal investigator · Wake Forest University Health Sciences

Homer Boushey, MD

principal investigator · University of California, San Francisco

Sally Wenzel, MD

principal investigator · University of Pittsburgh Medical Center

Christine Sorkness, MD

principal investigator · University of Wisconsin, Madison

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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