Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma

NCT00327197 | Terminated Phase 1

• 1 other identifier: RES100769
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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

Keywords

bronchoscopy; Sputum induction; Prednisolone; Asthma; biomarkers

Outcome Measures

Primary Outcomes (1)

• Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints

  biomarkers, vital signs, ECG

  Through 2 weeks of Prednisolone dosing

Secondary Outcomes (1)

• 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.

Study Arms (4)

Intermittent mild steroid-naïve asthmatic group

EXPERIMENTAL

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

Drug: Prednisolone; Procedure: Bronchoscopy

Mild to moderate persistent asthmatic group

EXPERIMENTAL

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.

Drug: Prednisolone; Procedure: Bronchoscopy

Severe asthma group

EXPERIMENTAL

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.

Drug: Prednisolone; Procedure: Bronchoscopy

Healthy subjects group

PLACEBO COMPARATOR

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

Procedure: Bronchoscopy

Interventions

Prednisolone 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.

Intermittent mild steroid-naïve asthmatic group; Mild to moderate persistent asthmatic group; Severe asthma group

Bronchoscopy PROCEDURE

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

Healthy subjects group; Intermittent mild steroid-naïve asthmatic group; Mild to moderate persistent asthmatic group; Severe asthma group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).
• Changed asthma medication within the 4 weeks prior to screening.
• Has had an asthma exacerbation in the previous month.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29550052 DERIVED

Related Links

• Results for study RES100769 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Asthma

Interventions

Prednisolone; Bronchoscopy

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2006
• First Posted: May 18, 2006
• Study Start: August 2, 2005
• Primary Completion: June 6, 2011
• Study Completion: June 6, 2011
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

GB (1)