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

NCT ID: NCT01161303

Last Updated: 2010-07-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 12 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2000-07-31
• Study Completion Date: 2003-06-30

Brief Summary

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.

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.

Conditions

Asthma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southampton

OTHER

Sponsor Role: collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

University of Southampton

Principal Investigators

Stephen T Holgate, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southampton

Locations

Southampton University Hospital Trust

Southampton, Hampshire, United Kingdom

Countries

United Kingdom

References

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

Reference Type: RESULT

Other Identifiers

SUHT-III-KSB

Identifier Type: -

Identifier Source: org_study_id