Montelukast and Nasal Epithelial Cell Inflammatory Responses in Asthma and Rhinitis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by University of Aberdeen.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
University of Aberdeen
ClinicalTrials.gov Identifier:
NCT01230437
First received: October 27, 2010
Last updated: October 28, 2010
Last verified: October 2010
  Purpose

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.


Condition
Asthma
Allergic Rhinitis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Effect of Montelukast on Inflammatory Responses of Nasal Epithelial Cells Cultured From Patients With Asthma, With and Without Concomitant Allergic Rhinitis

Resource links provided by NLM:


Further study details as provided by University of Aberdeen:

Primary Outcome Measures:
  • Effect of montelukast on nasal epithelial cell secretion in vitro. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • Nasal AEC will be cultured from 20 patients with asthma and 20 patients with asthma and concomitant allergic rhinitis.
    • Unstimulated, TNFα (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.


Secondary Outcome Measures:
  • Effect of 1-week montelukast withdrawal on clinical scores and pro-inflammatory cytokine output by nasal epithelial cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • 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.


Estimated Enrollment: 40
Study Start Date: January 2011
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
asthmatic patients taking montelukast
asthma with or without rhinitis

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

Ages Eligible for Study:   10 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01230437

Contacts
Contact: Garry M Walsh, PhD +44 (0) 1224 552786 g.m.walsh@abdn.ac.uk
Contact: Graham Devereux, MD, PhD +44 (0) 1224 558196 g.devereux@abdn.ac.uk

Locations
United Kingdom
University of Aberdeen Not yet recruiting
Aberdeen, United Kingdom, AB25 2ZD
Sponsors and Collaborators
University of Aberdeen
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Garry M Walsh, PhD University of Aberdeen
  More Information

Publications:
Responsible Party: Dr Garry Walsh, University of Aberdeen
ClinicalTrials.gov Identifier: NCT01230437     History of Changes
Other Study ID Numbers: MSD-36765-IISP, MT091 RGD 1265
Study First Received: October 27, 2010
Last Updated: October 28, 2010
Health Authority: Scotland: Scottish Executive Health Department

Keywords provided by University of Aberdeen:
montelukast
asthma
allergic rhinitis
nasal epithelial cells
inflammatory mediators

Additional relevant MeSH terms:
Asthma
Rhinitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Montelukast
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014