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

Asthma Clinical Trial

Official title:

Study to Investigate the Role of TNF-alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01161303
• Other study ID #: SUHT-III-KSB
• Status: Completed
• Phase: N/A
• First received: July 12, 2010
• Last updated: July 12, 2010
• Start date: July 2000
• Est. completion date: June 2003

Study information

• Verified date: July 2010
• Source: University Hospital Southampton NHS Foundation Trust.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2003
• Est. primary completion date: June 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Asthma

Locations

Country	Name	City	State
United Kingdom	Southampton University Hospital Trust	Southampton	Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Southampton NHS Foundation Trust.	University of Southampton

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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