Inhaled Corticosteroids on Airway Smooth Muscle in Asthma

September 12, 2019 updated by: Imperial College London

The Effect of Inhaled Corticosteroids (ICS) on Airway Smooth Muscle in Asthma

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 4

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
      • London, United Kingdom, SW3 6NP
        • Asthma lab, Royal Brompton Hospital, Sydney Street

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 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: overall
Drug: budesonide
inhaled budesonide (turbohaler) 400 micrograms twice a day for 4 weeks
Other Names:
  • pulmicort

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in ASM mass, proliferation and migration after ICS therapy; changes in chemokine release after ICS therapy
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in sub-basement membrane thickness and inflammatory cell count after ICS therapy
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

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

Sponsor

Imperial College London

Collaborators

Royal Brompton & Harefield NHS Foundation Trust

Investigators

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

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 (ACTUAL)

April 1, 2008

Primary Completion (ACTUAL)

December 1, 2010

Study Completion (ACTUAL)

March 1, 2011

Study Registration Dates

First Submitted

April 16, 2008

First Submitted That Met QC Criteria

April 18, 2008

First Posted (ESTIMATE)

April 21, 2008

Study Record Updates

Last Update Posted (ACTUAL)

September 13, 2019

Last Update Submitted That Met QC Criteria

September 12, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2007-006664-29
  • 07/H0803/239

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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