Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

NCT ID: NCT00359073

Last Updated: 2018-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2009-01-31

Brief Summary

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.

Detailed Description

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, however one problem with this approach is that once the clinical signs and symptoms appear, viral replication is well underway.

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Montelukast

montelukast (10 mg everyday)

Group Type: ACTIVE_COMPARATOR

montelukast

Intervention Type: DRUG

10 mg everyday

Placebo

Placebo comparator

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

like placebo

Interventions

montelukast

10 mg everyday

Intervention Type: DRUG

placebo

like placebo

Intervention Type: DRUG

Other Intervention Names

Singulair; like placebo

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James E Gern, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Kloepfer KM, DeMore JP, Vrtis RF, Swenson CA, Gaworski KL, Bork JA, Evans MD, Gern JE. Effects of montelukast on patients with asthma after experimental inoculation with human rhinovirus 16. Ann Allergy Asthma Immunol. 2011 Mar;106(3):252-7. doi: 10.1016/j.anai.2010.11.021. Epub 2011 Jan 13.

Reference Type: DERIVED

PMID: 21354028 (View on PubMed)

Related Links

http://www.medicine.wisc.edu/asthma/asthmamain

Allergy,Asthma and Pulmonary Clinical Research Unit website

Other Identifiers

31799

Identifier Type: OTHER

Identifier Source: secondary_id

H-2006-0173

Identifier Type: -

Identifier Source: org_study_id