AsthmaNCT00217854
Inflammatory Processes in the Airway of Asthmatics With Persistent Bronchial Hyperreactivity
A study testing Bronchoscopic in people with Asthma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Asthma
- What is being tested?
- Bronchoscopic
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2001to Feb 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Symptoms of asthma as defined by the American Thoracic Society (ATS) definition. This includes the following:
- 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
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: 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.
Read the 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.
- Conditions
- Asthma
- Being tested
- Bronchoscopic
- Keywords
- asthma, corticosteroids
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BronchoscopicProcedure or surgery
Bronchoscopic procedure
| Study group | Role | What they receive |
|---|---|---|
| Open label inhaled fluticasone | Other | Patients are treated with open label high dose fluticasone for 30 days then discontinued. Comparisons are pre- and post- treatment single arm. Receives: Procedure: Bronchoscopic |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in CD3 positive T cells in the airway submucosa
Measured: Measured at Week 4
Secondary outcomes (5)
inflammatory cell markers in the airway (CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase)
Measured: Measured at Week 4
RANTES expression in airway
Measured: Measured at Week 4
FEV1, peak expiratory flows
Measured: Measured at Week 4
methacholine PC20
Measured: Measured at Week 4
asthma symptom score
Measured: Measured at Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startSep 2001
- Primary completionFeb 2009
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Mario Castro, Washington University School of Medicine
- Investigators
- Mario Castro, Study chair, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00217854
- Sponsor's protocol ID
- 291
- Other IDs
- P50HL056419
- Status last verified
- Jun 2017
- First submitted
- 19 Sep 2005
- Last updated
- 26 Jun 2017
- Results posted
- No
Publications
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. doi: 10.1164/rccm.200208-960OC. Epub 2004 Jan 15.
PubMed 14726420
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Airway Inflammation: Natural Exacerbation of Asthma Induced by Glucocorticoid Withdrawal
- ClinicalTrials.gov ID
- NCT00217854
- Acronym / sponsor ID
- 291
- Conditions
- Asthma
- Keywords
- asthma, corticosteroids
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2001
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label inhaled fluticasone | Other | Procedure: BronchoscopicPatients are treated with open label high dose fluticasone for 30 days then discontinued. Comparisons are pre- and post- treatment single arm. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Symptoms of asthma as defined by the American Thoracic Society (ATS) definition. This includes the following:
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BronchoscopicBronchoscopic procedure | Procedure or surgery | Open label inhaled fluticasone |
Primary outcome
change in CD3 positive T cells in the airway submucosa
Time frame: Measured at Week 4
5 secondary outcomes
inflammatory cell markers in the airway (CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase)
Time frame: Measured at Week 4
RANTES expression in airway
Time frame: Measured at Week 4
FEV1, peak expiratory flows
Time frame: Measured at Week 4
methacholine PC20
Time frame: Measured at Week 4
asthma symptom score
Time frame: Measured at Week 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
- Background: PubMed 14726420Castro 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. doi: 10.1164/rccm.200208-960OC. Epub 2004 Jan 15.
- Click here for the Pulmonary and Critical Care Medicine WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Castro study chair
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchoscopic in people with Asthma, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in CD3 positive T cells in the airway submucosa (time frame: Measured at Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00217854, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2017; AzTrials last refreshed its copy on 7 Nov 2026.