Inhaled Corticosteroids on Airway Smooth Muscle in Asthma

This study has been withdrawn prior to enrollment.
(The study was withdrawn for administrative reasons)
Sponsor:
Collaborator:
Royal Brompton & Harefield NHS Foundation Trust
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00661973
First received: April 16, 2008
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Asthma
Drug: budesonide
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effect of Inhaled Corticosteroids (ICS) on Airway Smooth Muscle in Asthma

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Changes in ASM mass, proliferation and migration after ICS therapy; changes in chemokine release after ICS therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in sub-basement membrane thickness and inflammatory cell count after ICS therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: April 2008
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: budesonide
    inhaled budesonide (turbohaler) 400 micrograms twice a day for 4 weeks
    Other Name: pulmicort
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661973

Locations
United Kingdom
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
  More Information

No publications provided

Responsible Party: Professor Kian Fan Chung, Imperial College London
ClinicalTrials.gov Identifier: NCT00661973     History of Changes
Other Study ID Numbers: 2007-006664-29, 07/H0803/239
Study First Received: April 16, 2008
Last Updated: June 22, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
asthma
airway smooth muscle
inhaled corticosteroids

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014