The health condition studied will be asthma, the participants will be monitored during stable episodes and will subsequently undergo nasal inoculation with Rhinovirus for inducing loss of control/mild exacerbation.
Conditions
Interventions
Nasal inoculation with GMP Rhinovirus 16
Sponsors
Academic Medical Centre, Amsterdam
Eligibility
Inclusion criteria
Inclusion criteria: Asthma patients will be selected using the following inclusion criteria: • Age 18-50 years • History of episodic chest tightness and wheezing • Intermittent or mild to moderate persistent asthma according to the criteria by the Global Initiative for Asthma (Global Initiative of Asthma. www.ginasthma.org) • Non-smoking or stopped smoking more than 12 months ago and 5 pack years or less • Clinically stable, no exacerbations within last six weeks prior to study • Steroid-naïve or those participants who are currently not on corticosteroids and have not taken any corticosteroids by any dosing-routes within 6 weeks prior to the study or only using on-demand reliever therapy • Baseline pre-bronchodilator FEV1 ≥ 70% of predicted • Airway hyperresponsiveness, indicated by a positive methacholine bromide (MeBr) challenge test with PC20 3 mm • No other clinically significant abnormality on history and clinical examination • Able to give written and dated informed consent prior to any study-specific procedures Healthy subjects will be selected using the following inclusion criteria • Age 18-50 years • Non-smoking or stopped smoking more than 12 months ago and 5 pack years or less Steroid-naïve, non-atopic participants who are currently not on any maintenance (subjects using oral contraceptives can be accepted) • No maintenance medication • Baseline FEV1 ≥ 80% of predicted • Negative methacholine bromide (MeBr) challenge or PC20 ≥ 19.6 mg/ml • Negative skin prick test (SPT) to all of the 12 common aeroallergen extracts • Negative history of pulmonary and any other relevant disease • Able to give written and dated informed consent prior to any study-specific procedure
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participation in the study: • Women who are pregnant, lactating or have a positive urine pregnancy test at baseline visit • Participation in any clinical investigational drug treatment protocol within the preceding 5 half-lives of the drug (or 12 weeks if the half life is unknown) before the screening visit • Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the patient Furthermore the following additional exclusion criteria will be used in part 2 of the study: • RV16 titre > 1:8 in serum, measured at screening (visit 1) and also at Rhinovirus inoculation visit • History of clinical significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness • History of an asthma exacerbation within the last 6 weeks prior to the study • Has had any acute illness, including a common cold, within 4 weeks prior to visit 1 • Close contact with young children or with any immunosuppressed patients • Has donated blood or has had a blood loss of more than 450 mL within 60 days prior to screening visit 1 or plans to donate blood during the study. • Positive for any virus in nasal lavage at Rhinovirus inoculation day
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical markers and biomarkers of inflammatory origin from blood, exhaled breath, nasal lavage and urine. These include: •Lung function assessments such as Peak flow, Spirometry, Forced Oscillation Technique (FOT) and Fraction Exhaled Nitric Oxide that can be directly measured from the cases and the control subjects. •Biomarkers of eosinophilic and neutrophilic inflammation (peripheral blood counts, Eosinophil Cationic Protein: ECP, Myeloperoxidase: MPO), related chemokines and interleukins (IL-5, eotaxin, IL-8, etc.) that can be assayed in blood/Nasal Lavage (NAL). •Inflammatory low molecular weight compounds like bromo tyrosine, F2 isoprostanes, and lipid mediators like prostaglandins that can be analysed in exhaled breath/urine. •Exhaled Volatile Organic Compound (VOC) metabolomics profiles measured by GC-MS and SpiroNose that can be helpful in distinguishing asthmatics from healthy subjects and discriminating inflammatory phenotypes of asthma. •Inflammatory low molecular weight compounds, e.g. adenosines, nitro-tyrosines, malondialdehyde and others that can adequately be assessed in exhaled breath. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Time series fluctuations as derived from: Mean, Covariance, Skewness, Autocorrelation, Cross correlation etc. between different biomarkers and symptoms for about 10 days initially during the stable phase and subsequently prior and post virus challenge. • Multi Fractal De-trended Fluctuation Analysis on the time series data of biological markers. • Recurrence Quantification analysis to examine the correlation and recurrence pattern of fluctuations, if the data points are large enough to calculate embedding dimension and reconstruction delay. • Finally a multivariate probabilistic prediction model using the correlation exponent values for risk prediction. | — |
Contacts
Public ContactPeter J. Sterk
Dept. Pulmonology, F5-259 Academic Medical Center University of Amsterdam P.O. Box 22700
Outcome results
None listed