Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

montelukast

placebo

About this trial

This is an interventional prevention trial for Asthma focused on measuring asthma, leukotrienes, rhinovirus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Montelukast

Placebo

Arm Description

montelukast (10 mg everyday)

Placebo comparator

Outcomes

Primary Outcome Measures

Mean Asthma Symptom Score

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.

Secondary Outcome Measures

Peak Viral Shedding

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.

Sputum Eosinophil Count

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.

Full Information

NCT ID

NCT00359073

First Posted

July 28, 2006

Last Updated

March 12, 2018

Sponsor

University of Wisconsin, Madison

1. Study Identification

Unique Protocol Identification Number

NCT00359073

Brief Title

Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

Official Title

Effect of Montelukast on Experimentally-Induced RV16 Infection in Volunteers With Mild Asthma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

October 2006 (Actual)

Primary Completion Date

January 2009 (Actual)

Study Completion Date

January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Wisconsin, Madison

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

asthma, leukotrienes, rhinovirus

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Montelukast

Arm Type

Active Comparator

Arm Description

montelukast (10 mg everyday)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo comparator

Intervention Type

Drug

Intervention Name(s)

montelukast

Other Intervention Name(s)

Singulair

Intervention Description

10 mg everyday

Intervention Type

Drug

Intervention Name(s)

placebo

Other Intervention Name(s)

like placebo

Intervention Description

like placebo

Primary Outcome Measure Information:

Title

Mean Asthma Symptom Score

Description

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.

Time Frame

Day 7

Secondary Outcome Measure Information:

Title

Peak Viral Shedding

Description

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.

Time Frame

Baseline and 7 days

Title

Sputum Eosinophil Count

Description

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.

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James E Gern, MD

Organizational Affiliation

University of Wisconsin, Madison

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Wisconsin

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Citations:

PubMed Identifier

21354028

Citation

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.

Results Reference

derived

Links:

URL

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

Description

Allergy,Asthma and Pulmonary Clinical Research Unit website

Asthma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial