Inflammatory Processes in the Airway of Asthmatics With Persistent Bronchial Hyperreactivity

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mario Castro, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00217854
First received: September 19, 2005
Last updated: June 27, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to examine inflammatory processes in the airway of moderate to severe persistent asthmatics who have persistent bronchial hyperreactivity despite chronic administration of inhaled glucocorticoids.


Condition Intervention
Asthma
Procedure: Bronchoscopic

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Mechanisms of Airway Inflammation: Natural Exacerbation of Asthma Induced by Glucocorticoid Withdrawal

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • change in CD3 positive T cells in the airway submucosa [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • inflammatory cell markers in the airway (CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
  • RANTES expression in airway [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
  • FEV1, peak expiratory flows [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
  • methacholine PC20 [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
  • asthma symptom score [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2001
Study Completion Date: February 2011
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Bronchoscopic
    Bronchoscopic procedure
Detailed Description:

BACKGROUND:

The Inhaled Glucocorticoid Withdrawal Protocol will investigate abnormalities in the asthmatic airway that occur in the setting of a "natural" endogenous exacerbation. It is known that chronic treatment with inhaled glucocorticoids causes a nearly complete disappearance of inflammatory cells from the airway and improvement in bronchial hyperreactivity, yet such patients have persistent bronchial hyperreactivity. Withdrawal of inhaled glucocorticoids causes a worsening of bronchial hyperreactivity. These observations suggest that a chronic derangement in the asthmatic airway might exist, which is unmasked by withdrawal of inhaled glucocorticoids and which reinitiates the inflammatory process. These "persistent" abnormalities in the asthmatic airway may be seen during quiescent stages of chronic asthma even when airway inflammatory changes are not evident. The abnormalities may be seen during the period of treatment with inhaled glucocorticoids or they may appear as one of the first signs after the withdrawal of inhaled glucocorticoids, thereby initiating the recurrence of asthma and promoting inflammation.

DESIGN NARRATIVE:

The purpose of this study is to examine inflammatory processes in the airway of moderate to severe persistent asthmatics who have persistent bronchial hyperreactivity despite chronic administration of inhaled glucocorticoids. Each participant will undergo bronchoscopic procedures and have assessment of bronchial hyperreactivity at the following two time points: 1) during treatment with inhaled fluticasone; and 2) after acute withdrawal of inhaled fluticasone.

The primary outcome of this study is the change in CD3 positive T cells in the airway submucosa.

The key secondary outcomes are as follows: 1) other inflammatory cell markers in the airway (e.g., CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase); 2) RANTES (regulated on activation, normal T expressed and secreted) expression in airway; 3) FEV1 peak expiratory flows; 4) methacholine PC20; and 5) asthma symptom score.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptoms of asthma as defined by the American Thoracic Society (ATS) definition. This includes the following:

    1. history of episodic shortness of breath (with or without associated wheezing) in association with reversible obstructive airways disease with at least a 20% decrement in FEV1 and FVC (from predicted values) that is documented at some time point by pulmonary function tests
    2. an improvement in expiratory flow rates of at least 15% of predicted values after inhalation of a beta-2 selective bronchodilator medication or other previous treatment (e.g. corticosteroids)
  • The diagnosis may also be confirmed by an abnormal bronchospastic response to methacholine or exercise as described by Cherniak
  • FEV1 greater than or equal to 70% of predicted value at time of study entry
  • Regular use of inhaled corticosteroids at time of study entry (at least 400 mcg of Beclomethasone or equivalent)

Exclusion Criteria:

  • Used inhaled cromolyn (Intal) or nedocromil (Tilade) in the month prior to study entry
  • History of severe asthma requiring intubation
  • Any cardiopulmonary or neurologic abnormality with which the risk of performing the procedure would outweigh the potential benefits (other than asthma)
  • Upper respiratory tract infection or clinical evidence of a sinus infection during the month preceding the test
  • History of cigarette smoking within the 5 years prior to study entry or greater than 10 pack-years total
  • Pregnant or refuses to undergo urine pregnancy testing if female of child-bearing age (women of childbearing potential will not be challenged [methacholine challenge] unless they have had a menstrual period in the last 10 days or a negative pregnancy test within 2 weeks or are practicing adequate contraception)
  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: NCT00217854

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Study Chair: Mario Castro Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Mario Castro, Professor of Medicine and Pediatrics, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00217854     History of Changes
Other Study ID Numbers: 291, P50HL056419, P50 HL056419
Study First Received: September 19, 2005
Last Updated: June 27, 2012
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Asthma
Bronchial Hyperreactivity
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014