RECRUITINGOBSERVATIONAL

Airway Remodeling and Rhinovirus in Asthmatics

Comparison of Airway Remodeling Mediators Following Experimental Human Rhinovirus Infection in Subjects With Mild to Moderate Asthma and Healthy, Non-asthmatic Control Subjects

About This Trial

Human rhinovirus is also called the "common cold virus" because it causes at least half of all of the common colds experienced each year. In patients with asthma, getting a rhinovirus infection can cause worsening of asthma symptoms. Although these symptoms are well known, researchers do not fully understand how the virus worsens these asthma symptoms, nor do they really know whether virus infection causes longer term structural changes (often referred to as airway remodeling) in the airways. This study plans to address and answer these questions. Doing so will provide the researchers with a better understanding of how to treat the worsening of asthma that are caused by human rhinovirus infections. The epithelial cell is the cell that lines the surface of your airways from your nose down to your lungs, and is also the cell type that gets infected by rhinovirus. At present, it is thought that the virus causes symptoms by changing epithelial cell biology in a way that causes airway inflammation. Some of these inflammatory molecules are also thought to cause scarring (remodeling) of the airways, which over time, may lead to a loss of lung function. In order to examine how the virus causes inflammation, many earlier studies have used experimental infection with the virus and have measured various markers of inflammation. The purpose of this study is to compare the levels of inflammatory and remodeling products in the airways of study participants with mild to moderate asthma and healthy, non-asthmatic subjects after infection with rhinovirus (the common cold virus).

Who May Be Eligible (Plain English)

Asthma Cohort Who May Qualify: - Male or female volunteers with intermittent or persistent mild to moderate allergic asthma, as defined by GINA guidelines. - Between ≥18 and ≤ 65 years of age - Objective evidence of variable airflow limitation (≥12% and at least 200mL post-bronchodilator reversibility from baseline) and airway hyperresponsiveness (PC20 methacholine \<16mg/mL) at screening or within past 5 years - Spirometry at baseline shows FEV1 ≥ 60% of predicted; FEV1/FVC ≥ 0.40 - Atopic, as evidenced by positive skin prick tests to ≥1 common aero-allergen, where positive is defined by a wheal of ≥2 mm greater than the negative control - Not be exposed to sensitizing seasonal allergens for at least 4 weeks before visit 2 - Asthma symptoms controlled by either inhaled beta 2-agonists alone, or by low or moderate dose (≤800 μg of budesonide or equivalent per day) inhaled corticosteroid (ICS) administered either as monotherapy or in a fixed-dose combination with a long-acting beta 2-agonist (LABA) - Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking - In good general health (other than asthma) without clinically significant medical history of other comorbidities, and a BMI of ≤ 35 kg/m2. Healthy, Non-asthmatic Cohort Who May Qualify: - Male or female volunteers in good general health, without clinically significant medical history and a BMI of ≤ 35 kg/m2 - Between ≥18 and ≤ 65 years of age - Non-asthmatic, as defined by history and normal spirometry (FEV1 ≥80% predicted; FEV1/FVC ≥ 0.75) - Normal airway responsiveness (PC20 methacholine not detected at, or less than, 16 mg/mL) - Non-atopic, as determined by skin prick tests to common aero-allergens, where a positive test is defined as a wheal of ≥2 mm greater than the negative control. - Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Asthma Cohort Inclusion Criteria: * Male or female volunteers with intermittent or persistent mild to moderate allergic asthma, as defined by GINA guidelines. * Between ≥18 and ≤ 65 years of age * Objective evidence of variable airflow limitation (≥12% and at least 200mL post-bronchodilator reversibility from baseline) and airway hyperresponsiveness (PC20 methacholine \<16mg/mL) at screening or within past 5 years * Spirometry at baseline shows FEV1 ≥ 60% of predicted; FEV1/FVC ≥ 0.40 * Atopic, as evidenced by positive skin prick tests to ≥1 common aero-allergen, where positive is defined by a wheal of ≥2 mm greater than the negative control * Not be exposed to sensitizing seasonal allergens for at least 4 weeks before visit 2 * Asthma symptoms controlled by either inhaled beta 2-agonists alone, or by low or moderate dose (≤800 μg of budesonide or equivalent per day) inhaled corticosteroid (ICS) administered either as monotherapy or in a fixed-dose combination with a long-acting beta 2-agonist (LABA) * Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking * In good general health (other than asthma) without clinically significant medical history of other comorbidities, and a BMI of ≤ 35 kg/m2. Healthy, Non-asthmatic Cohort Inclusion Criteria: * Male or female volunteers in good general health, without clinically significant medical history and a BMI of ≤ 35 kg/m2 * Between ≥18 and ≤ 65 years of age * Non-asthmatic, as defined by history and normal spirometry (FEV1 ≥80% predicted; FEV1/FVC ≥ 0.75) * Normal airway responsiveness (PC20 methacholine not detected at, or less than, 16 mg/mL) * Non-atopic, as determined by skin prick tests to common aero-allergens, where a positive test is defined as a wheal of ≥2 mm greater than the negative control. * Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking * Willing to participate in study and be able to provide written consent prior to starting the study. Exclusion Criteria (both cohorts): * Presence of neutralizing antibodies to HRV-39 * Current pregnancy or positive urine pregnancy test at screening * Use of any of the following medications: antihistamines, leukotriene antagonists, inhaled anticholinergics, non-steroidal anti-inflammatories, antibiotics, and over the counter 'cold' and influenza remedies, in preceding 4 weeks prior to visit 2. * Current acute or chronic illness (including infection) or recent recovery (within 4 weeks of visit 3) from acute illness which could, in the opinion of the Investigator, alter inflammatory responses (e.g., flu, cold or other respiratory infection, etc.). * Autoimmune disease or immunodeficiency * Any other significant concomitant medical issue, or findings on physical examination or medical history that, in the opinion of the study physician, may pose additional risks from participation in the study (including undergoing bronchoscopy), or which may impact the quality or interpretation of the data obtained from the study. * Inability or unwillingness of a potentially eligible study participant to give written informed consent. * Unable or unwilling to adhere to protocol-defined study visit schedule and/or other protocol requirements.

Treatments Being Tested

BIOLOGICAL

HRV-39

We will use a US Food and Drug Administration (FDA) approved Good Manufacturing Practices (GMP)-grade HRV-39 for our proposed study. Use of this GMP-grade HRV-39 viral stock ensures compliance with recent regulatory agency requirements which, beginning in 2001, have mandated that HRV preparations used for human inoculation be made under Good Manufacturing Practices (GMP). This proposed clinical study will allow us to address fundamental questions regarding the nature, kinetics and potential mechanisms of upper and lower airway inflammatory responses in subjects with well-controlled mild-moderate asthma and in healthy, non-asthmatic control subjects; a better understanding of these mechanisms may lead to new paradigms in the treatment of virally-induced airway remodeling and asthma exacerbations.

Locations (1)

University of Calgary

Calgary, Alberta, Canada