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

NCT01537133 | Completed Results DMC

• 2 other identifiers: AsthmaNet 003U10HL098115
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Asthma; Atopy

Outcome Measures

Primary Outcomes (3)

• Microbial Community Richness

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

  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).

  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.

  baseline and after 6 weeks of treatment

Study Arms (4)

Inhaled corticosteroid

EXPERIMENTAL

Fluticasone (250 mcg/puff, one puff, twice a day)

Drug: fluticasone

Placebo

PLACEBO COMPARATOR

Placebo fluticasone (one puff, twice a day)

Drug: Placebo

Healthy Control

NO INTERVENTION

Atopic Non-asthmatics

NO INTERVENTION

Interventions

fluticasone DRUG

Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day

Also known as: Flovent 250

Inhaled corticosteroid

Placebo DRUG

Dry Powder Inhaler: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (9)

University of California, San Francisco, Adult

San Francisco, California, 94143-0130, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27110, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Pittsburgh, Adult

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Wisconsin

Madison, Wisconsin, 53972, United States

Location

Related Publications (1)

• 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.

  PMID: 32298699 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: David Mauger
• Organization: Penn State University

dtm5@psu.edu

717-531-7178

Study Officials

• 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 University Health Sciences

  PRINCIPAL INVESTIGATOR

• Homer Boushey, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Sally Wenzel, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Christine Sorkness, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Public Health Sciences

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 23, 2012
• Study Start: October 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 30, 2016
• Results First Posted: November 30, 2016

Record last verified: 2016-11

Locations

US (9)