- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00279136
Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
Study Overview
Status
Conditions
Detailed Description
Rationale. Asthma is associated with variable airways obstruction and airways inflammation. It is generally assumed that inflammatory mechanisms are promoting airway narrowing, by stimulating airway smooth muscle and by geometrical changes of the airway wall. Healthy subjects are very effectively protected against stimuli of airway narrowing, by mechanisms that are apparently failing in asthma. The most potent inhibitor of airway narrowing in healthy subjects is taking a deep inspiration. This prevents and reverses bronchoconstriction (DI-induced bronchoprotection and -bronchodilation, respectively), which is less effective or absent in asthma. The DI-induced inhibition of airway narrowing in normal subjects is presumably due to relaxation of smooth muscle after mechanical stretch or to the release of relaxant mediators (such as endogenous NO). Such mechanisms might have become impaired in asthma, secondary to e.g. mechanical uncoupling of smooth muscle from the surrounding parenchyma (e.g. by congestion or edema), by altered structure and function of airway smooth muscle, and/or by reduced inhibitory mediator release.
It can be postulated that the impaired response to deep inspiration is a central pathophysiological feature of asthma at all ages. Therefore, we believe that it is imperative to address this, by identifying and restoring these inhibitory pathways in patients with asthma.
Hypotheses.
We hypothesize that DI-induced bronchoprotection and -broncho¬dilation:
- are associated with cellular and morphological features of airways inflammation,
- can be restored by deep insufflation rather than deep inspiration, and by pharmacological interventions aimed to reduce microvascular congestion or to increase endogenous nitric oxide synthesis..
Design and methods. To examine to what extent DI-responses differ between asthma and COPD in adulthood, and whether this is associated with features of airways inflammation and changes in smooth muscle function. 12 Adult patients with asthma and 12 with COPD will undergo single-dose methacholine challenge, with prohibition of DI's or 5 DI's prior to challenge in a cross-over design, measuring airways resistance. On a separate day bronchial biopsies will obtained with immunohistochemistry for inflammatory cell markers, vascularity, microvascular leakage, myosin light chain kinase, NO-synthases, and arginase.
Study Type
Enrollment
Contacts and Locations
Study Contact
- Name: Peter J. Sterk, MD, PhD
- Phone Number: +31 71 526 3578
- Email: p.j.sterk@lumc.nl
Study Contact Backup
- Name: Annelies M. Slats, MD
- Phone Number: +31 71 526 3734
- Email: a.m.slatts@lumc.nl
Study Locations
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Leiden, Netherlands, NL-2300 RC
- Recruiting
- Leiden University Medical Center
-
Contact:
- Peter J. Sterk, MD, PhD
- Phone Number: +31 71 526 3578
- Email: p.j.sterk@lumc.nl
-
Contact:
- Annelies M. Slats, MD
- Phone Number: +31 71 526 3734
- Email: a.m.slats@lumc.nl
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Principal Investigator:
- Peter J. Sterk, MD, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Asthma according to GINA criteria (www.ginasthma.org)
- COPD according to GOLD criteria (www.goldcopd.org)
Exclusion Criteria:
- nonsmoking
- inhaled or oral steroid therapy
Study Plan
How is the study designed?
Design Details
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Peter J. Sterk, MD, PhD, Leiden University Medical Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AF 3.2.02.34, DIACON
- Grant AF 3.2.02.34
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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