Official Title: “Effect of Montelukast on Experimentally-Induced RV16 Infection in Volunteers With Mild Asthma”

People with asthma may have asthma worsening when they have an upper respiratory infection due to a virus or a common cold. Leukotrienes are increased in nasal secretions from children with Respiratory Syncytial Virus (RSV) and lung washings during times of acute lung inflammation. Experimental virus exposure in adults is also associated with increases in nasal leukotrienes.

The degree to which leukotrienes play a role in asthma worsening is unknown.There is information linking leukotrienes to viral infections, allergic inflammation, and asthma exacerbation.This information supports the hypothesis that virus-induced leukotrienes contribute to the severity of respiratory infections and in susceptible individuals, lead to lower airway obstruction and exacerbations of asthma. We propose to use montelukast in an experimental viral challenge model to explore this hypothesis.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2009

Viral infections are important causes of wheezing illnesses throughout childhood and in adults with asthma. There has been progress in identifying mechanisms and risk factors for severe respiratory symptoms, and in particular, wheezing. Given this close relationship, it would be attractive to apply antiviral strategies to the prevention and treatment of asthma, and both RV and RSV are obvious targets. Unfortunately, attempts at developing an RSV vaccine have so far been unsuccessful, and vaccination to prevent RV infection does not seem to be feasible due to the large number of serotypes. Antiviral medications have been tested in clinical trials,53-57 however one problem with this approach is that once the clinical signs and symptoms appear, viral replication is well underway. As a result, reductions in respiratory symptoms or the duration of illness are modest.56 The other potential therapeutic approach for respiratory viral infections would be to selectively inhibit pro-inflammatory immune responses induced by the virus. The beneficial effects of systemic glucocorticoids indicate that this approach is valid; the challenge will be to develop treatments with greater efficacy and a reduced potential for adverse effects. The large body of information linking cysteinyl leukotrienes to viral infections, allergic inflammation, and asthma exacerbations, strongly supports the hypothesis that virus-induced leukotrienes contribute to the severity of respiratory infections and in susceptible individuals, lead to lower airway obstruction and exacerbations of asthma. We propose to use montelukast in an experimental viral challenge model to explore this hypothesis.

Intervention(s) in this Clinical Trial

• Drug: montelukast
  • 10 mg QD
• Drug: placebo
  • like placebo

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • montelukast (10 mg QD)
• Placebo Comparator: 2

Primary Measures

• Infection related change in asthma control

Secondary Measures

• Secondary outcome measures include cold symptoms, viral shedding and cellularity in the nasal secretions and induced sputum.

Inclusion Criteria:

• A subject with mild persistent asthma is eligible for participation in the study if all of the following inclusion criteria apply:
• Male or female with no health concerns that might affect the outcome of the study
• Age 18-65 range
• diagnosis of mild persistent asthma based on clinical findings such as cough, wheeze and shortness of breath
• a history of asthma for at least six months prior to screening
• FEV1> 80% of predicted
• presence of allergy based on at least one positive prick skin test when tested with a standard panel of common allergens
• ability to produce sputum when induced during the baseline assessments
• asthma medications consisting of only inhaled short acting B-agonist taken as needed
• reversible airways disease as indicated by > 12% reversibility post B-agonist or
• methacholine hyperresponsiveness (PC20 < 8 mg/ml)
• ability to give valid informed consent to participate by signing and dating a written consent form

Exclusion Criteria:

• A subject is not eligible to participate in this study if any of the following exclusion criteria apply:
• History of severe episodes of asthma with respiratory infections
• Screening serum RV16 antibody titer > 1
• Current smoker or has a smoking history exceeding 5 pack years
• Currently receiving immunotherapy
• Currently participating in another clinical trial or has participated in an investigational drug trial within one month of screening
• Unable, in the judgment of the investigator, to comply with directions and/or tolerate the procedures required for participation in this trial
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• Regular use of an asthma controller such as montelukast or an inhaled corticosteroid.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Wisconsin, Madison

Overall Clinical Trial Officials and Contacts

James E Gern, MD Principal Investigator University of Wisconsin, Madison  

Overall Contact: Cheri A Swenson, BS (608) 262-5189 cas@medicine.wisc.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00359073

Study ID Number: 31799

ClinicalTrials.gov Identifier: NCT00359073

Health Authority: United States: Institutional Review Board

Allergy,Asthma and Pulmonary Clinical Research Unit website