An Investigation of Tumor Necrosis Factor (TNF)-Alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

This study has been completed.
Sponsor:
Collaborator:
University of Southampton
Information provided by:
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT01161303
First received: July 12, 2010
Last updated: NA
Last verified: July 2010
History: No changes posted

July 12, 2010
July 12, 2010
July 2000
June 2003   (final data collection date for primary outcome measure)
Not Provided
Not Provided
No Changes Posted
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An Investigation of Tumor Necrosis Factor (TNF)-Alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures
Study to Investigate the Role of TNF-alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

We have developed in vitro systems including primary epithelial cell cultures and explant cultures of bronchial tissues to study the interaction between the bronchial mucosa and allergens. This approach involves culturing bronchial biopsies under optimal conditions and stimulate them with allergens thus enabling us to perform a dynamic study without the need of performing several bronchoscopies and will allow the testing of unapproved substances, which could, otherwise, not be delivered, in vivo.

We wish to apply these ex vivo bronchial culture systems to assess cytokine release in moderately severe asthmatics and evaluate the effects of blocking TNF-alpha signalling using anti TNF-alpha monoclonal antibodies.

Volunteers with moderately severe asthma will be recruited and carefully characterized in terms of lung function, asthma symptom scores, medication usage and allergen sensitivity (by blood and skin tests). If suitable, they will then be asked to withdraw their corticosteroids for a week with careful monitoring of the symptoms and peak flows before undergoing fibreoptic bronchoscopy as was carried out in the previous explant study. Bronchial brushings and biopsies will be carried out as per standard technique used in University medicine. Primary epithelial cell cultures will be established from bronchial brushings and will be used for optimising the dose of anti TNF-alpha required for inhibition of TNF-alpha induced responses. The biopsies will be placed in either culture medium alone, allergen extract or allergen extract plus anti TNF-alpha antibody and cultured for 24 hours. The biopsies will then be either snap frozen in liquid nitrogen for analysis of cytokines or processed for immunohistochemical analysis. The supernatants from each study will be recovered and analysed for cytokine (IL-5, IL-8, IL-13, MIP 1 alpha and RANTES) release by ELISA.

Observational
Observational Model: Cohort
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:
  • bronchial brushings and biopsies
  • Blood
Non-Probability Sample

Primary care clinic

Asthma
Not Provided
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
June 2003
June 2003   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Moderately severe asthmatics
  • Male or female
  • Uses inhaled beclomethasone 400-1000 mcg or equivalent
  • Documented positive skin test to common allergens and
  • FEV1 of >60% predicted

Exclusion criteria:

  • Smokers
  • Subjects with an acute asthmatic episode in the last 6 weeks
  • Other significant clinical illnesses
  • Pregnant women
  • Those sensitive to lignocaine
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01161303
SUHT-III-KSB
No
Professor S.T. Holgate, University of Southampton
University Hospital Southampton NHS Foundation Trust.
University of Southampton
Principal Investigator: Stephen T Holgate, MD University of Southampton
University Hospital Southampton NHS Foundation Trust.
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP