Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma

NCT ID: NCT00327197

Last Updated: 2017-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-02
• Study Completion Date: 2011-06-06

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intermittent mild steroid-naïve asthmatic group

Asymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 \>=80% and normal peak expiratory flow between attacks will be included.

Group Type: EXPERIMENTAL

Prednisolone

Intervention Type: DRUG

Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days.

Bronchoscopy

Intervention Type: PROCEDURE

All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

Mild to moderate persistent asthmatic group

Subjects 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.

Group Type: EXPERIMENTAL

Prednisolone

Intervention Type: DRUG

Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days.

Bronchoscopy

Intervention Type: PROCEDURE

All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

Severe asthma group

Subjects 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.

Group Type: EXPERIMENTAL

Prednisolone

Intervention Type: DRUG

Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days.

Bronchoscopy

Intervention Type: PROCEDURE

All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

Healthy subjects group

Non-asthmatic and non-smokers with FEV1 \> 85% predicted, on no regular medication.

Group Type: PLACEBO_COMPARATOR

Bronchoscopy

Intervention Type: PROCEDURE

All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

Interventions

Prednisolone

Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days.

Intervention Type: DRUG

Bronchoscopy

All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• History of asthma with exclusion of other significant pulmonary disease.
• Body Mass Index between 19-31 kg.m-2.
• Subjects will be assigned to group 1(mild to moderate) or Group 2 (severe asthmatics) depending on their Lung Function test results.

• Having participated within 30 days or 5 half-lives, whichever is longer of the first dose in a study using new molecular entity, or the first dose in any other study investigating drugs or having participated within one month of the first dose in a study with invasive procedures.
• History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessments.
• History of abnormal bruising or bleeding.
• History of alcohol or drug abuse.
• Doing night-shift work within at least 5 days prior to dosing until completion of the study.
• Anticoagulants except low dose of Aspirin (80 mg per day) (for bronchoscopy).
• Beta blockers except for low dose Atenolol (25 mg/day) or Metoprolol (50 mg/day) (for bronchoscopy).
• Use of Cytochrome P450 inhibitors.
• History of hypersensitivity to any of the following medications: Lidocaine, Fentanyl, Versed, Demerol, Midazolam, Epinephrine, Flumazenil and Naloxone.
• History of hypersensitivity to bronchodilator (such as Albuterol).

Exclusion Criteria

• As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study.
• History of drug or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation.
• Subject is female who is pregnant or lactating.

• Changed asthma medication within the 4 weeks prior to screening.
• Has had an asthma exacerbation in the previous month.
• Known sensitivity or allergy to prednisolone.
• Current use or use within the previous 3 months of oral corticosteroids.
• Current use of Methotrexate, cyclosporine and PDE inhibitors
• History of tuberculosis, diabetes mellitus, osteoporosis, severe hypertension, glaucoma , severe affective disorder and peptic ulceration.

• Changed asthma medication within the 4 weeks prior to screening.
• Has had an asthma exacerbation in the previous month.
• sensitivity or allergy to prednisolone.
• History of tuberculosis, diabetes mellitus, osteoporosis, hypertension, glaucoma, severe affective disorder and peptic ulceration.
• Current use or use within the previous 4 weeks of oral prednisolone or equivalent of greater than 20mg daily.
• Current use of Methotrexate, cyclosporin.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Leicester, Leicestershire, United Kingdom

Countries

United Kingdom

References

Siddiqui S, Shikotra A, Richardson M, Doran E, Choy D, Bell A, Austin CD, Eastham-Anderson J, Hargadon B, Arron JR, Wardlaw A, Brightling CE, Heaney LG, Bradding P. Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis. J Allergy Clin Immunol. 2018 Nov;142(5):1457-1468. doi: 10.1016/j.jaci.2017.12.982. Epub 2018 Mar 14.

Reference Type: DERIVED

PMID: 29550052 (View on PubMed)

Other Identifiers

RES100769

Identifier Type: -

Identifier Source: org_study_id