Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

• ClinicalTrials.gov Identifier: NCT00359073
• Recruitment Status: Completed
• First Posted: August 1, 2006
• Results First Posted: March 13, 2018
• Last Update Posted: March 13, 2018
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: July 28, 2006
• First Posted Date: August 1, 2006
• Results First Submitted Date: August 17, 2010
• Results First Posted Date: March 13, 2018
• Last Update Posted Date: March 13, 2018
• Actual Study Start Date: October 2006
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2018)

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.

• Original Primary Outcome Measures (submitted: July 28, 2006): Infection related change in the Asthma Control Diary Score. (Juniper ACD)

Current Secondary Outcome Measures (submitted: March 12, 2018)

• 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.
• 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.

• Original Secondary Outcome Measures (submitted: July 28, 2006): Secondary outcome measures include cold symptoms, viral shedding and cellularity in the nasal secretions and induced sputum.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Asthma

Intervention

• Drug: montelukast
  10 mg everyday
  Other Name: Singulair
• Drug: placebo
  like placebo
  Other Name: like placebo

Study Arms

• Active Comparator: Montelukast
  montelukast (10 mg everyday)
  Intervention: Drug: montelukast
• Placebo Comparator: Placebo
  Placebo comparator
  Intervention: Drug: placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2018): 25
• Original Enrollment (submitted: July 28, 2006): 40
• Actual Study Completion Date: January 2009
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00359073
• Other Study ID Numbers: H-2006-0173; 31799 ( Other Identifier: PI )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Wisconsin, Madison
• Study Sponsor: University of Wisconsin, Madison
• Collaborators: Not Provided

Investigators

• Principal Investigator: James E Gern, MD; University of Wisconsin, Madison

• PRS Account: University of Wisconsin, Madison
• Verification Date: March 2018