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This study is designed to characterize in detail the clinical, physiologic, and inflammatory features of Human Rhinovirus (HRV) infection in healthy volunteers without underlying lung disease while also evaluating the safety of HRV administrations.
Full description
The majority of severe exacerbations of asthma and need for hospitalizations are triggered by infection with respiratory viruses. Of these, rhinovirus is the most commonly implicated virus. Furthermore, there is evidence that viral infections exert synergistic effects with other stimuli to provoke asthma symptoms such as exposure to allergens and air pollutants. Experimental HRV infection studies have yielded important insights into the underlying disease mechanisms of viral-induced asthma exacerbations, and have been integral to identifying candidates for the development of new therapies. These studies have been safely conducted in both healthy and susceptible populations (those with underlying airway disease such as asthma and chronic obstructive pulmonary disease (COPD)), for more than 60 years.
Much of the understanding of the clinical course of HRV infection is derived from experimental infections of healthy human volunteers. In these studies, subjects were inoculated intranasally with up to 10,000 [tissue culture infectious dose (TCID)] TCID50 of HRV, the most commonly used strains being HRV-16 and HRV-39. Experimental HRV infection produces the hallmark clinical features of the common cold including rhinorrhea and nasal obstruction. Respiratory symptoms typically develop 1-2 days after inoculation. Cold symptom scores generally peak 2-4 days post infection and return to baseline within 1 week in most infected subjects. HRV infection induces changes in inflammatory cell recruitment, nasal cytokine levels, and gene expression, which occur concurrently with clinical symptoms.
While the symptoms of HRV infection are typically limited to the upper respiratory tract in healthy subjects, those with underlying airway disease such asthma and COPD are more likely to exhibit an augmented and prolonged response to HRV infection with lower airway involvement. HRV is the leading viral cause of exacerbations of asthma and COPD; therefore, the response of these populations to HRV infection has been the focus of a number of studies. Although most studies in asthmatics have been performed in inhaled corticosteroid-naïve subjects, a recent study performed in subjects whose asthma was well controlled with inhaled corticosteroids demonstrates the safety of experimental HRV infection in this population. This model has also been employed in conjunction with other exposure models such as allergen challenge and pollutant exposure. There are several ongoing and recently completed clinical trials registered with ClinicalTrials.gov that utilize the HRV infection model. Of these, several employ the HRV-16 strain (ClinicalTrials.gov Identifiers: NCT01769573, NCT01466738, NCT01823640, NCT03073837, NCT03296917, NCT01704040, NCT02910401) being used in this study. Both healthy and asthmatic volunteers are represented in these clinical trials.
In summary, the experimental HRV infection model has proven to be a safe and valuable tool for examining various aspects of HRV biology. Due to the limitations associated with animal models of asthma and COPD, and the lack of animal species that are permissive for HRVs, experimental infection of humans with HRV has been integral for examining the pathophysiology of virus-induced exacerbations of asthma and COPD. Although experimental HRV-infection results in a reduction in lung function for some asthmatics and COPD patients, no serious adverse events have been reported using this model.
The goal of this study is to establish the experimental HRV-infection model in this research center using a viral inoculum referred to as RG-HRV-16. This strain was used in a recently-completed safety and dosing study (NCT01769573). Our study would provide the pilot data needed for the design of subsequent studies evaluating innate immune responses to HRV infection in asthmatics, modulation of HRV-induced responses by inhaled pollutants, and efficacy of novel therapeutic agents.
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Inclusion criteria
Age 18-45 years of either gender
Non-smoker (less than 10 cigarettes per month for at least the prior 3 years)
Negative pregnancy test (for females as applicable)
Oxygen saturation of > 94% and blood pressure with systolic value between 140-90 mm Hg and diastolic between 80-55 mm Hg
Willingness to hold all nasal medications (including, but not limited to, nasal steroids or nasal spray decongestants), oral antihistamines and leukotriene inhibitors for at least 1 week prior to Day 0 and continuing throughout the remaining study period.
Negative Allergy Skin Test (AST) at a separate screening visit performed prior to study enrollment, University of North Carolina Institutional Review Board (UNC IRB) approved study # 98-0799, Database and Screening Protocol for Research Studies of the Center for Environmental Medicine and Lung Biology (CEMALB). (Results from AST performed within the past 12 months as part of another study protocol or AST reports from testing performed by the subject's Medical Doctor (MD) within the past 12 months will also be accepted.)
Negative methacholine inhalation challenge as performed in the separate screening protocol. (Less than a 20% decrease in Forced Exhaled Volume at 1 second (FEV1) at a maximum methacholine concentration of 10 mg/ml).
Normal lung function, defined as (NHANES III predicted set):
No nasal symptoms, based on respiratory questionnaire
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23 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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