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

September 19, 2005
June 27, 2012
September 2001
February 2009   (final data collection date for primary outcome measure)
change in CD3 positive T cells in the airway submucosa [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00217854 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Inflammatory Processes in the Airway of Asthmatics With Persistent Bronchial Hyperreactivity
Mechanisms of Airway Inflammation: Natural Exacerbation of Asthma Induced by Glucocorticoid Withdrawal

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.

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.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Asthma
Procedure: Bronchoscopic
Bronchoscopic procedure
Not Provided
Castro M, Bloch SR, Jenkerson MV, DeMartino S, Hamilos DL, Cochran RB, Zhang XE, Wang H, Bradley JP, Schechtman KB, Holtzman MJ. Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway. Am J Respir Crit Care Med. 2004 Apr 1;169(7):842-9. Epub 2004 Jan 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
February 2011
February 2009   (final data collection date for primary outcome measure)

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)
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00217854
291, P50HL056419, P50 HL056419
Not Provided
Mario Castro, Washington University School of Medicine
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Study Chair: Mario Castro Washington University School of Medicine
Washington University School of Medicine
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP