Mechanisms of Interplay Between Allergy and Viruses in Asthma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Imperial College London
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01773590
First received: November 30, 2012
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

The aim of this study is to investigate the mechanisms of interplay between allergy (IgE and Th2 mediated inflammation) and virus infection in the development of asthma, as well as the risk and severity of acute exacerbations of asthma. Understanding these mechanisms should identify new approaches for novel therapies for the prevention of asthma development and for prevention/treatment of asthma exacerbations. Such treatment has potential to have a major impact on patient quality of life and to result in enormous reductions in health care costs.

A human model will be used to identify dysregulated genes/proteins and determine relationships with disease outcomes. This study will compare lower airway responses between asthmatic and healthy control subjects undergoing rhinovirus (RV) experimental infection (subjects will be infected with rhinovirus as part of the study). This will have the dual advantage of investigating mechanisms in the most natural model possible, as well as developing a better model for testing novel therapeutic approaches. The investigators will analyse the samples from both subject groups, to determine their relevance to the human disease. Any genes/proteins shown to be dysregulated and related to disease outcomes in the human model will be very strong candidates for immediate translation into human intervention studies.

Up to 12 asthmatic and/or healthy subjects will be recruited for a preliminary pilot study. These subjects will be ineligible to enter the main study due to the presence of neutralizing antibody to RV16 (~50% of subjects otherwise suitable for the study). These subjects will meet all other inclusion/exclusion criteria for the main study. The 12 participants will undergo tests including a single bronchoscopy, nasal sampling and blood tests allowing for optimisation of all sample processing techniques. They will not be infected with RV-16.

In the main study the investigators will aim to study up to 15 healthy volunteers and 15 volunteers with moderate asthma (all on inhaled steroid treatment). Subjects will undergo a single baseline bronchoscopy 2 weeks prior to inoculation with the RV16 virus. Following infection with the virus participants will be required to attend for regular sample collection including 2 further bronchoscopies post-infection. Patients will be followed until convalescence 6 weeks post infection.


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: Mechanisms of Interplay Between Allergy and Viruses in Asthma: A 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:
  • Host response to RV challenge [ Time Frame: Prior to and 0-42 days post challenge ] [ Designated as safety issue: No ]
    The host response to RV challenge will be assessed daily for 8 days using methods including symptom diaries, lung function, detection of mediators in nasal and bronchial lining fluid, characterisation of different cell types in bronchoalveolar lavage as determined by flow cytometry. This will be compared with findings at baseline, day 11, 15 and up to 42 days post challenge.


Estimated Enrollment: 42
Study Start Date: February 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Asthmatics
Rhinovirus Infection
Other: Rhinovirus Infection
Healthy Volunteers
Rhinovirus Infection
Other: Rhinovirus Infection

  Eligibility

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

Inclusion Criteria:

Inclusion criteria for Asthmatic subjects:

  • Age 18-55 years
  • Doctor diagnosis of Asthma
  • Histamine PC20 < 8 µg/ml (or <12 µg/ml and bronchodilator response ≥ 12%) and worsening asthma symptoms with infection since last change in asthma therapy
  • Atopic on skin testing
  • Treatment comprising ICS or combination inhaler (LABA+ICS)

    *subjects on inhaled corticosteroids must be on a daily dose of 400mcg fluticasone or equivalent.

  • An Asthma Control Questionnaire (ACQ) score of > 0.75.

Inclusion criteria for healthy controls:

  • Age 18-55 years
  • No history or clinical diagnosis of asthma
  • No history of allergic rhinitis or eczema
  • Negative responses on skin prick testing
  • PC20 > 8 µg/ml and bronchodilator response <12%
  • Absence of current or previous history of significant respiratory disease
  • Absence of significant systemic disease

Exclusion Criteria:

Exclusion criteria for Asthmatic subjects:

  • Smoking history over past 6 months
  • Negative skin prick tests
  • 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
  • Asthma exacerbation or viral illness within the previous 6 weeks
  • Treatment with oral steroids now or in the previous 3 months
  • Current use of nasal spray, anti-histamine, anti-leukotrienes
  • Antibodies to rhinovirus 16 in a titre >1:2

Exclusion criteria for healthy controls:

  • Any clinically relevant abnormality on screening or detected significant systemic disease
  • A current or previous diagnosis of asthma
  • Any positive skin prick test
  • Current symptoms of allergic rhinitis
  • History of eczema or allergic rhinitis
  • Pregnant or nursing women
  • Common cold within the previous 8 weeks
  • Treatment with oral or inhaled steroids now or in the previous 3 months; current use of long-acting β-agonists, nasal spray, anti-histamine, leukotrienes or tiotropium.
  • Shortness of breath score at screening over 1 or total lower respiratory tract score over 7
  • Antibodies to rhinovirus 16 in a titre >1:2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773590

Contacts
Contact: Jaideep Dhariwal, MBBS BSc jaideep.dhariwal@imperial.ac.uk

Locations
United Kingdom
National Heart and Lung Institute Not yet recruiting
London, United Kingdom
Principal Investigator: Sebastian Johnston         
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Sebastian Johnston National Heart and Lung Institute
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01773590     History of Changes
Other Study ID Numbers: 12/LO/1278, 12/LO/1278
Study First Received: November 30, 2012
Last Updated: January 18, 2013
Health Authority: United Kingdom: National Institute for Health Research

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 August 21, 2014