MedPath

Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma

Phase 1
Terminated
Conditions
Asthma
Interventions
Procedure: Bronchoscopy
Registration Number
NCT00327197
Lead Sponsor
GlaxoSmithKline
Brief Summary

To evaluate and compare the expression and change in expression of key severe asthma targets at baseline in mile to moderate asthmatics vs. severe asthmatic subjects.

To evaluate and compare the airway pathology at baseline and changes in airway pathology in relation to asthma severity.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
47
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Severe asthma groupPrednisoloneSubjects with severe persistent asthma. They will be on either: high inhaled corticosteroid (CS \>=1000 microgram fluticasone daily or equivalent) or on high dose inhaled CS plus oral CS (no more than 20 milligrams predisolone a day). The subjects should have at least one ( if on oral steroids) or two (if only on inhaled steroids) of the following: 1) FEV1\<80% and FEV1/FVC ratio \<70% 2) more than 25% variability in peak expiratory flow 3) daily symptoms ± nocturnal symptoms 4) severe exacerbations of \>= twice a year in at least one of the last two years.
Mild to moderate persistent asthmatic groupBronchoscopySubjects with mild to moderate persistent asthma on low to moderate dose of inhaled corticosteroid (200-500 microgram fluticasone propionate daily or equivalent), an FEV1 \>= 80% predicted (post-bronchodilator), and less than 20% variability in peak expiratory flow.
Intermittent mild steroid-naïve asthmatic groupBronchoscopyAsymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 \>=80% and normal peak expiratory flow between attacks will be included.
Healthy subjects groupBronchoscopyNon-asthmatic and non-smokers with FEV1 \> 85% predicted, on no regular medication.
Severe asthma groupBronchoscopySubjects with severe persistent asthma. They will be on either: high inhaled corticosteroid (CS \>=1000 microgram fluticasone daily or equivalent) or on high dose inhaled CS plus oral CS (no more than 20 milligrams predisolone a day). The subjects should have at least one ( if on oral steroids) or two (if only on inhaled steroids) of the following: 1) FEV1\<80% and FEV1/FVC ratio \<70% 2) more than 25% variability in peak expiratory flow 3) daily symptoms ± nocturnal symptoms 4) severe exacerbations of \>= twice a year in at least one of the last two years.
Mild to moderate persistent asthmatic groupPrednisoloneSubjects with mild to moderate persistent asthma on low to moderate dose of inhaled corticosteroid (200-500 microgram fluticasone propionate daily or equivalent), an FEV1 \>= 80% predicted (post-bronchodilator), and less than 20% variability in peak expiratory flow.
Intermittent mild steroid-naïve asthmatic groupPrednisoloneAsymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 \>=80% and normal peak expiratory flow between attacks will be included.
Primary Outcome Measures
NameTimeMethod
Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpointsThrough 2 weeks of Prednisolone dosing

biomarkers, vital signs, ECG

Secondary Outcome Measures
NameTimeMethod
Expression of airway and systemic biomarkers. Relationship between changes in target expression and clinical measures of disease activity. Relationship between steady state plasma exposure of prednisolone and pharmacodynamic biomarkers.Through 2 weeks of prednisolone dosing.

biomarkers

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

Leicester, Leicestershire, United Kingdom

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