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

July 12, 2010 updated by: University Hospital Southampton NHS Foundation Trust

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Southampton University Hospital Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Primary care clinic

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Southampton NHS Foundation Trust

Collaborators

University of Southampton

Investigators

  • Principal Investigator: Stephen T Holgate, MD, University of Southampton

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Babu KS, Puddicombe S, Shaw TJ, Howell T, Wilson SJ, Holgate ST, Davies DE. Am J Respir Crit Care Med. 169 (7): A801, 2004

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2000

Primary Completion (Actual)

June 1, 2003

Study Completion (Actual)

June 1, 2003

Study Registration Dates

First Submitted

July 12, 2010

First Submitted That Met QC Criteria

July 12, 2010

First Posted (Estimate)

July 13, 2010

Study Record Updates

Last Update Posted (Estimate)

July 13, 2010

Last Update Submitted That Met QC Criteria

July 12, 2010

Last Verified

July 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SUHT-III-KSB

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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