Montelukast and Nasal Epithelial Cell Inflammatory Responses in Asthma and Rhinitis

Asthma Clinical Trial

Official title:

The Effect of Montelukast on Inflammatory Responses of Nasal Epithelial Cells Cultured From Patients With Asthma, With and Without Concomitant Allergic Rhinitis

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01230437
• Other study ID #: MSD-36765-IISP
• Secondary ID: MT091 RGD 1265
• Status: Unknown status
• Phase: N/A
• First received: October 27, 2010
• Last updated: October 28, 2010
• Start date: January 2011
• Est. completion date: December 2011

Study information

• Verified date: October 2010
• Source: University of Aberdeen
• Contact: Garry M Walsh, PhD
• Phone: +44 (0) 1224 552786
• Email: g.m.walsh[@]abdn.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 40
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Allergic Rhinitis
• Asthma
• Rhinitis
• Rhinitis, Allergic

Locations

Country	Name	City	State
United Kingdom	University of Aberdeen	Aberdeen

Sponsors (2)

Lead Sponsor	Collaborator
University of Aberdeen	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of montelukast on nasal epithelial cell secretion in vitro.	Nasal AEC will be cultured from 20 patients with asthma and 20 patients with asthma and concomitant allergic rhinitis.; Unstimulated, TNFa (a surrogate for viral infection, a well known trigger of exacerbations) or allergen stimulated secretion of IL-6, IL-10, INFgamma TGFbeta, GM-CSF, eotaxin 1 & 2, RANTES and IL-8 by NEC will be measured. The in vitro inhibitory effects of a concentration range (10-6M to 10-10M) of montelukast will be assessed.	12 months
Secondary	Effect of 1-week montelukast withdrawal on clinical scores and pro-inflammatory cytokine output by nasal epithelial cells	The secondary outcome of the study will be to examine the effect of withdrawal montelukast for 1-week on clinical scores and pro-inflammatory cytokine/ chemokine secretion by cultured NEC in montelukast-responsive patients with asthma (20 subjects) and asthma/AR (20 subjects).; The clinical scores and NEC secretory responses in these patients following montelukast withdrawal will be compared with the responses generated in the primary study i.e., while taking montelukast.	12 months