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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
  Purpose

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.


Condition
Asthma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Study to Investigate the Role of TNF-alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

Resource links provided by NLM:

MedlinePlus related topics: Asthma
U.S. FDA Resources

Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Biospecimen Retention:   Samples With DNA
  • bronchial brushings and biopsies
  • Blood

Enrollment: 12
Study Start Date: July 2000
Study Completion Date: June 2003
Primary Completion Date: June 2003 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Primary care clinic

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01161303

Locations
United Kingdom
Southampton University Hospital Trust
Southampton, Hampshire, United Kingdom, SO16 6YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
University of Southampton
Investigators
Principal Investigator: Stephen T Holgate, MD University of Southampton
  More Information

No publications provided

Responsible Party: Professor S.T. Holgate, University of Southampton
ClinicalTrials.gov Identifier: NCT01161303     History of Changes
Other Study ID Numbers: SUHT-III-KSB
Study First Received: July 12, 2010
Last Updated: July 12, 2010
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
Asthma
TNF alpha
epithelial cell culture

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 June 13, 2013