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Inhaled Corticosteroids on Airway Smooth Muscle in Asthma

Sponsor
Imperial College London (Other)
Overall Status
Withdrawn
CT.gov ID
NCT00661973
Collaborator
Royal Brompton & Harefield NHS Foundation Trust (Other)
0
Enrollment
1
Location
1
Arm
35
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective is to evaluate how treatment with inhaled corticosteroids (ICS) affects the characteristics of airway smooth muscle (ASM) cells from asthmatic subjects. Our hypothesis is that airway smooth muscle cell dysfunction plays an important role in the pathogenesis of asthma, and that treatment with inhaled corticosteroids reverses the abnormalities in airway smooth muscle cell function.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Aims and Objectives

Most of the work published to date on the effect of steroids on ASM has been carried out in animal models or in in vitro experiments. We would like to evaluate in vivo whether abnormalities in ASM function respond to ICS. Because ASM cells can be obtained from bronchial biopsies obtained via bronchoscopy, we will examine endobronchial biopsies from corticosteroid-naïve, mild asthmatic subjects. In particular, we will examine whether ICS have any effect ASM mass, proliferation and expression of different contractile proteins (α-actin and myosin) and chemokines, and will assess in vitro the response of ASM cells to stimulation by TGF-β and IL-1β. We will also examine the effect of dexamethasone on chemokine release and induced proliferation in vitro before and after treatment with ICS.

We will examine the effect of inhaled corticosteroids in 12 subjects with mild asthma. The subjects will be studied during a baseline period and again after receiving treatment with inhaled corticosteroid therapy with Budesonide Turbohaler (400 ug bd) for 4 weeks. The results of these two periods will be compared.

There will be 5 study visits. In the first two visits, the subjects will undergo spirometry with reversibility testing, a methacholine challenge test, skin prick tests and IgE levels, measurement of exhaled nitric oxide, and subjects will complete an Asthma Control Questionnaire and an Asthma Quality of Life Questionnaire. The third visit will be the day admission for the bronchoscopy. They will be given asthma control diary cards to complete during the 4-week treatment with ICS and receive their ICS turbohaler. At visit 4, they will have repeat spirometry and methacholine challenge to assess if there has been a change secondary to treatment with ICS. The final visit will be for the second bronchoscopy, when the dairy card and ICS inhaler will be collected, and the subjects will complete the Asthma Control and Quality of Life questionnaire.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
The Effect of Inhaled Corticosteroids (ICS) on Airway Smooth Muscle in Asthma
Actual Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Dec 1, 2010
Actual Study Completion Date :
Mar 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: overall

Drug: budesonide
inhaled budesonide (turbohaler) 400 micrograms twice a day for 4 weeks
Other Names:
  • pulmicort

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Changes in ASM mass, proliferation and migration after ICS therapy; changes in chemokine release after ICS therapy [4 weeks]

    Secondary Outcome Measures

    1. Changes in sub-basement membrane thickness and inflammatory cell count after ICS therapy [4 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Physician diagnosis of asthma

    • Age 18-60

    • Intermittent asthma symptoms < once/week

    • FEV1>80% of predicted

    • Not on inhaled corticosteroid therapy

    Exclusion Criteria:

    • Previous long-term use of inhaled corticosteroids (within 1 year of entry into study)

    • Past history of hypersensitivity to budesonide

    • Current smokers, or less than 3 years since quitting smoking

    • Less than 4 weeks from an exacerbation

    • On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin

    • Concomitant anti-IgE therapy

    • Pregnancy

    • Previous bronchoscopy within three months of this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Asthma lab, Royal Brompton Hospital, Sydney Street London United Kingdom SW3 6NP

    Sponsors and Collaborators

    • Imperial College London
    • Royal Brompton & Harefield NHS Foundation Trust

    Investigators

    • Principal Investigator: Kian F Chung, MBBS FRCP MD DSc, Imperial College London

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Imperial College London
    ClinicalTrials.gov Identifier:
    NCT00661973
    Other Study ID Numbers:
    • 2007-006664-29
    • 07/H0803/239
    First Posted:
    Apr 21, 2008
    Last Update Posted:
    Sep 13, 2019
    Last Verified:
    Sep 1, 2019
    Keywords provided by Imperial College London
    asthma
    airway smooth muscle
    inhaled corticosteroids
    Additional relevant MeSH terms:
    Asthma
    Budesonide

    Study Results

    No Results Posted as of Sep 13, 2019