AsthmaNCT00186693
How Airway Remodeling and Hyperresponsiveness Contribute to Airflow Obstruction in Asthma
An observational study of Asthma, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
Trial summary
Airway hyperresponsiveness is a characteristic feature of the asthma. It is known that there is an association between airway hyperresponsiveness and eosinophilic airway inflammation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2006to Jun 2009
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: adults with asthma
Who may be able to join
- adults age 18 - 65 years
- stable asthma, defined as no need for new medical intervention in previous 4 weeks
- pre FEV1 > or = to 70% and able to have a methacholine challenge
- hyper-responsiveness as measured by methacholine challenge PC20 < or = 16 mg/ml
- steroid naive or stable inhaled corticosteroid medication in previous 8 weeks
- symptomatic treatment with bronchodilators permitted
Show all 10Show fewer
- able to give written informed consent
- no other active/unstable medical conditions as judged by investigator
- subjects must be suitable for bronchoscopy in opinion of the investigator
- female subjects must no be pregnant, nursing or unwilling to use appropriate contraception
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Airway hyperresponsiveness is a characteristic feature of the asthma. It is known that there is an association between airway hyperresponsiveness and eosinophilic airway inflammation. However, even though inflammation can be reduced with appropriate asthma therapy, it is typical that airway hyperresponsiveness improves only modestly with treatment. The determinants of airway hyperresponsiveness are unclear.
It is also not clear as to the site of airway narrowing in asthma. It is hypothesized that airways beyond the 4th order have the greatest resistance.
We hope to determine the relationships between the airway inflammation, remodeling of the airway and airway hyperresponsiveness. Through local instillation of methacholine at bronchoscopy we will be able to study proximal and distal airways and the extent to which they constrict in vivo
Read the detailed description
Airway hyperresponsiveness (AHR) is a characteristic feature of the asthmatic condition in humans. There is an association between AHR and eosinophilic airway inflammation. However, even though eosinophilic inflammation can be abolished with appropriate therapy, it is typical that AHR improves only modestly with treatment. The determinants of AHR are poorly understood. Recent data implicate mediators such as the cytokine Interleukin-13 (IL-13), structural changes to the airway wall (remodeling), increased contractility of airway smooth muscle cells (ASMC) and loss of mechanical connections or tethering, as potential factors contributing to AHR.
There is also uncertainty around the site of airway narrowing in asthma. In normal airways, bronchii around the 4th order have the greatest contribution to total resistance. It is hypothesized that the site of greatest resistance is moved distally in asthma and might even involve quite small airways close to the level of terminal bronchioles. Non-invasive methods to assess airway caliber in vivo are still unproven. One untested concern is that the airways of subjects with severe AHR have the potential to close completely putting them at risk of severe and even fatal airflow obstruction.
We propose to study AHR in humans with asthma: we will determine the relationships between AHR and (i) eosinophilic inflammation in the airway (sputum cellularity) via sputum induction, (ii) soluble mediators of inflammation (IL-13, IL-4, IL-5), (iii) remodeling of the airway wall (sub-epithelial fibrosis, ASMC accumulation)via biopsy. In addition we will compare measurements of AHR assessed by inhalation challenge with the results of direct, local installation of methacholine. At bronchoscopy, methacholine is delivered to the airway and bronchoconstriction is assessed directly. This method will allow study of proximal and distal airways, identification of heterogeneity of responses among airways and the extent to which human airways can constrict in vivo.
- Conditions
- Asthma
- Keywords
- Airway remodeling, Asthma, Hyper-responsiveness
- Medical subject headings
- Asthma, Airway Remodeling
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startSep 2006
- Study completionJun 2009 (estimated)
Why it stopped: never received funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Healthcare Hamilton
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- Gerard Cox, MB FRCPC FRCPI, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00186693
- Sponsor's protocol ID
- 05-2453
- Status last verified
- Jul 2006
- First submitted
- 10 Sep 2005
- Last updated
- 26 Jul 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How Airway Remodeling and Hyperresponsiveness Contribute to Airflow Obstruction in Asthma
- ClinicalTrials.gov ID
- NCT00186693
- Acronym / sponsor ID
- 05-2453
- Conditions
- Asthma
- Keywords
- Airway remodeling, Asthma, Hyper-responsiveness
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: never received funding
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- St. Joseph's Healthcare HamiltonUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Sep 2006
- Study completion
- Jun 2009 (estimated)
- First posted
- 16 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.
Airway hyperresponsiveness is a characteristic feature of the asthma. It is known that there is an association between airway hyperresponsiveness and eosinophilic airway inflammation. However, even though inflammation can be reduced with appropriate asthma therapy, it is typical that airway hyperresponsiveness improves only modestly with treatment. The determinants of airway hyperresponsiveness are unclear.
It is also not clear as to the site of airway narrowing in asthma. It is hypothesized that airways beyond the 4th order have the greatest resistance.
We hope to determine the relationships between the airway inflammation, remodeling of the airway and airway hyperresponsiveness. Through local instillation of methacholine at bronchoscopy we will be able to study proximal and distal airways and the extent to which they constrict in vivo
Detailed description
Airway hyperresponsiveness (AHR) is a characteristic feature of the asthmatic condition in humans. There is an association between AHR and eosinophilic airway inflammation. However, even though eosinophilic inflammation can be abolished with appropriate therapy, it is typical that AHR improves only modestly with treatment. The determinants of AHR are poorly understood. Recent data implicate mediators such as the cytokine Interleukin-13 (IL-13), structural changes to the airway wall (remodeling), increased contractility of airway smooth muscle cells (ASMC) and loss of mechanical connections or tethering, as potential factors contributing to AHR.
There is also uncertainty around the site of airway narrowing in asthma. In normal airways, bronchii around the 4th order have the greatest contribution to total resistance. It is hypothesized that the site of greatest resistance is moved distally in asthma and might even involve quite small airways close to the level of terminal bronchioles. Non-invasive methods to assess airway caliber in vivo are still unproven. One untested concern is that the airways of subjects with severe AHR have the potential to close completely putting them at risk of severe and even fatal airflow obstruction.
We propose to study AHR in humans with asthma: we will determine the relationships between AHR and (i) eosinophilic inflammation in the airway (sputum cellularity) via sputum induction, (ii) soluble mediators of inflammation (IL-13, IL-4, IL-5), (iii) remodeling of the airway wall (sub-epithelial fibrosis, ASMC accumulation)via biopsy. In addition we will compare measurements of AHR assessed by inhalation challenge with the results of direct, local installation of methacholine. At bronchoscopy, methacholine is delivered to the airway and bronchoconstriction is assessed directly. This method will allow study of proximal and distal airways, identification of heterogeneity of responses among airways and the extent to which human airways can constrict in vivo.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- adults with asthma
Key inclusion criteria (10 listed)
- adults age 18 - 65 years
- stable asthma, defined as no need for new medical intervention in previous 4 weeks
- pre FEV1 > or = to 70% and able to have a methacholine challenge
- hyper-responsiveness as measured by methacholine challenge PC20 < or = 16 mg/ml
- steroid naive or stable inhaled corticosteroid medication in previous 8 weeks
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2011.
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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.
Gerard Cox, MB FRCPC FRCPI principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
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 10 inclusion and 0 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: withdrawn, as of the sponsor's last update on 26 Jul 2011. 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 Canada. 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 was withdrawn before enrolling participants, so there are no results.
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.
Where can I read the original study information?
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 Jul 2011.