Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

March 12, 2018 updated by: University of Wisconsin, Madison

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo comparator
Drug: placebo
like placebo
Other Names:
  • like placebo
Active Comparator: Montelukast
montelukast (10 mg everyday)
Drug: montelukast
10 mg everyday
Other Names:
  • Singulair

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Asthma Symptom Score
Time Frame: Day 7
Asthma symptom scores were assessed twice per day with subjects completing a validated daytime diary card before bed and a nocturnal diary card on awakening. Subjects answered 4 questions about their asthma symptoms (0, none of the time; 6, all of the time). Daily score were calculated as the average of the 4 questions and an overall score for the week was assessed as the average of the daily scores. Time frame measurement was Day 7.
Day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Viral Shedding
Time Frame: Baseline and 7 days
Viral shedding was measured in both groups. Viral titers from nasal lavage were calculated after 4 tissue culture tubes containing WI38 cells (human lung diploid cells) were inoculated for each serial 10-fold dilution of samples and incubated while rolling at 33 degrees Celsius for 10 days (measurement for analysis was taken at baseline and 7 days). Tubes were read at baseline and 7 days later. TCID50 was calculated as the concentration that was capable of infecting 50% of the tubes. Viral titers are expressed as TCID50 per milliliter. Time frame measurement was at baseline and 7 days.
Baseline and 7 days
Sputum Eosinophil Count
Time Frame: 14 days
Sputum was collected from both groups over 14 days after inoculation with the cold virus. Cell counts and differentials were made from sputum samples after treatment with 0.1% dithiothreitol. Eosinophils were counted and are expressed as as percentage of cells (percent of the total number counted) at the 14 day timepoint.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Wisconsin, Madison

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2006

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

July 28, 2006

First Submitted That Met QC Criteria

July 28, 2006

First Posted (Estimate)

August 1, 2006

Study Record Updates

Last Update Posted (Actual)

March 13, 2018

Last Update Submitted That Met QC Criteria

March 12, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-2006-0173
  • 31799 (Other Identifier: PI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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