Clinical trial NCT01230437: Montelukast and Nasal Epithelial Cell Inflammatory Responses in Asthma and Rhinitis
Official title: The Effect of Montelukast on Inflammatory Responses of Nasal Epithelial Cells Cultured From Patients With Asthma, With and Without Concomitant Allergic Rhinitis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Allergic Rhinitis
Keywords: montelukast
asthma
allergic rhinitis
nasal epithelial cells
inflammatory mediators
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-10-29
Enrollment: 40
Sex: ALL
Minimum age (years): 10
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For the primary study the investigators will identify 40 patients (aged 10-60) with with stable physician confirmed mild/moderate asthma (Steps 1-4 of BTS/SIGN guidelines \[3\]) with \<10 pack-year smoking histories. Twenty of the subjects will have asthma and concomitant allergic rhinitis (asthma/AR) and 20 will have asthma alone.

Brief summary: The airways of the lung are lined by specialised cells called airway epithelial cells. As well as being at the interface between the lungs and the air we breathe; airway epithelial cell (AEC) function is altered in people with respiratory diseases such as asthma. AEC secrete many mediators that contribute to asthma symptoms and these also contribute to asthmatic inflammation in the lungs. The study of such cells is difficult because of their location deep in the lungs. Nasal airway epithelial cells provide a useful and easily accessible model of model of lower airway cells. This study will examine whether the asthma medication Singulair (montelukast) can inhibit the inflammatory secretions of nasal AEC of asthmatic patents who also have allergic rhinitis compared with patients who have asthma alone. We will also examine if montelukast has differential modulating effects in these two patient groups.

Detailed description: Hypothesis

The inflammatory secretory profile of nasal airway epithelial cells (NEC) cultured from asthmatics with concomitant allergic rhinitis (AR) will differ from that of NEC from patients with asthma alone. Treatment (in vitro and in vivo) with montelukast may have differential modulating effects in these two patient groups.

For the primary objective of this proposal we will use nasal AEC from asthmatics with or without concomitant AR as to ascertain differences in pro-inflammatory cytokine and chemokine production between these two groups and determine whether in vitro treatment with montelukast has a differential modulating effect on NEC secretion. In the secondary pilot study any modulating effects by montelukast on AEC secretion in vitro will be correlated with any in vivo response to montelukast withdrawal. This sub study will provide pilot data indicating whether in vivo response to montelukast can be predicted from in vitro effects on NEC.

Eligibility criteria: Inclusion Criteria:

* stable physician confirmed mild/moderate asthma (Steps 1-4 of BTS/SIGN guidelines \<10 pack-year smoking histories Currently taking montelukast with a documented clinical history of benefit

Exclusion Criteria:

* Nasal corticosteroid therapy

Primary outcomes:
measure: Effect of montelukast on nasal epithelial cell secretion in vitro.
timeFrame: 12 months
Secondary outcomes:
measure: Effect of 1-week montelukast withdrawal on clinical scores and pro-inflammatory cytokine output by nasal epithelial cells
timeFrame: 12 months
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: University of Aberdeen
Study officials:
affiliation: University of Aberdeen
name: Garry M Walsh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McDougall CM, Blaylock MG, Douglas JG, Brooker RJ, Helms PJ, Walsh GM. Nasal epithelial cells as surrogates for bronchial epithelial cells in airway inflammation studies. Am J Respir Cell Mol Biol. 2008 Nov;39(5):560-8. doi: 10.1165/rcmb.2007-0325OC. Epub 2008 May 15.