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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
dave mauger, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01537133
First received: February 9, 2012
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Asthma
Atopy
Drug: fluticasone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • microbial community composition [ Time Frame: after 6 weeks of treatment ] [ Designated as safety issue: No ]

    Descriptors of microbial community composition at baseline, and before and after ICS treatment intervention:

    • Richness (number of different bacterial taxa identified)
    • Evenness (distribution of the relative abundance of the taxa identified)
    • Diversity (a function of richness and evenness)
    • Presence and relative abundance of specific bacterial taxa


Enrollment: 84
Study Start Date: October 2012
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inhaled corticosteroid
Fluticasone (250 mcg/puff, one puff, twice a day)
Drug: fluticasone
Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day
Other Name: Flovent 250
Placebo Comparator: Placebo
Placebo fluticasone (one puff, twice a day)
Drug: Placebo
Dry Powder Inhaler: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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:

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01537133

Locations
United States, California
University of California, San Francisco, Adult
San Francisco, California, United States, 94143-0130
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, North Carolina
Duke University School of Medicine
Durham, North Carolina, United States, 27110
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
University of Pittsburgh, Adult
Pittsburgh, Pennsylvania, United States, 15213
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53972
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital
Principal Investigator: Lewis Smith, MD Northwestern Memorial Hospital
Principal Investigator: Richard Martin, MD National Jewish Health
Principal Investigator: Mario Castro, MD Washington University School of Medicine
Principal Investigator: Monica Kraft, MD Duke University
Principal Investigator: Stephen Peters, MD Wake Forest School of Medicine
Principal Investigator: Homer Boushey, MD University of California, San Francisco
Principal Investigator: Sally Wenzel, MD University of Pittsburgh
Principal Investigator: Christine Sorkness, MD University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: dave mauger, Professor of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01537133     History of Changes
Other Study ID Numbers: AsthmaNet 003, U10HL098115
Study First Received: February 9, 2012
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 28, 2014