Mechanisms of Rhinovirus Induced Asthma Exacerbations

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by Imperial College London.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT01159782
First received: July 8, 2010
Last updated: July 22, 2010
Last verified: July 2010
  Purpose

We, the investigators, hypothesise that there are distinct gene profiles in rhinovirus-induced acute exacerbations of asthma. We further hypothesise that these changes in gene expression involve both known mediators of the asthma phenotype as well as other molecules not previously associated with asthma.

The primary objective of this study is to use gene array analysis to determine differentially expressed genes in bronchial epithelial cells and alveolar macrophages from normal and asthmatic subjects before and during rhinovirus infection in vivo. A secondary objective is to determine whether any altered expressions are related to symptom severity, virus load, lung function or airway inflammation in vivo.

We plan to recruit 45 subjects: 15 healthy volunteers, 15 asthmatics naïve to inhaled corticosteroid therapy, and 15 asthmatics on inhaled corticosteroids who will undergo two bronchoscopies, one prior to infection with rhinovirus and the second 4 days post inoculation. Bronchial brushings, biopsies and bronchoalveolar lavage (BAL) will be performed. RNA will be extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and purified by passage through RNeasy columns (Qiagen, Valencia, CA). Exon 1.0ST array chips (Affymetrix, Santa Clara, CA) will be used to analyse changes in gene expression. These are the most powerful genome expression tools available with 1.4 million probe sets and over 5.5 million features per array. Genes found to be significantly upregulated will be confirmed by quantitative RT-PCR.

Using a novel method of collecting undiluted bronchial epithelial lining fluid (bronchosorption) large numbers of proteins will be measured with a MesoScale Discovery multiplexed array system (MesoScale Discovery, Gaithersburg, Md) allowing further confirmation of the gene array results as well as providing in vivo evidence of dysregulated protein production in asthmatics. Gene expression and protein levels will be correlated with viral load, symptom scores, lung function and airway inflammation in vivo.

This study represents the first comprehensive evaluation of changes in bronchial epithelial gene expression during rhinovirus infection in vivo and therefore has the potential to provide significant insights into the host response in asthma and identify potential novel targets for further evaluation.


Condition Intervention
Rhinovirus Infection in Asthma
Other: Rhinovirus infection

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Human Model of Rhinovirus Induced Acute Asthma Exacerbations

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • differentially expressed genes in bronchial epithelial cells and alveolar macrophages from normal and asthmatic subjects before and during rhinovirus infection [ Time Frame: april 2012 ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: October 2009
Estimated Study Completion Date: April 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Asthma, Healthy
Asthmatics or Healthy Volunteers
Other: Rhinovirus infection
All subjects (asthmatic and non asthmatic healthy)will be infected with Rhinovirus 16.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for atopic asthmatics:

  • Age 18-55 years
  • Doctor diagnosis of Asthma
  • PC20 < 8 µg/ml and worsening asthma symptoms with infection since last change in asthma therapy.
  • Atopic on skin testing
  • Treatment comprising short acting beta agonist (SABA) only (steroid naïve group) or SABA + inhaled corticosteroid (ICS) * (steroid treated group)

    • subjects on inhaled corticosteroids must be on a daily dose of between 100mcg and 1000mcg fluticasone or equivalent.

Exclusion Criteria:

  • Smoking history over past 6 months or > 5 py history
  • Current symptoms of allergic rhinitis
  • Current or previous history of significant respiratory disease (other than asthma)
  • Any clinically relevant abnormality on screening or detected significant systemic disease
  • Pregnant or breastfeeding women
  • Contact with infants or elderly at home or at work
  • Exacerbation or virus within the previous 6 weeks
  • Treatment with oral steroids now or in the previous 3 months
  • Current use of nasal spray, anti-histamine, anti-leukotriene
  • Antibodies to rhinovirus 16 in a titre >1:2
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01159782

Locations
United Kingdom
National Heart and Lung Institute Recruiting
London, England, United Kingdom, W2 1PG
Contact: David Jackson       d.jackson@imperial.ac.uk   
Principal Investigator: Sebastian Johnston         
Sponsors and Collaborators
Imperial College London
  More Information

No publications provided

Responsible Party: Professor Sebastian Johnston, Imperial College London
ClinicalTrials.gov Identifier: NCT01159782     History of Changes
Other Study ID Numbers: 09/H0712/59
Study First Received: July 8, 2010
Last Updated: July 22, 2010
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014