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Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma

This study has been terminated.
(The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00327197
First Posted: May 18, 2006
Last Update Posted: August 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

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.


Condition Intervention Phase
Asthma Drug: Prednisolone Procedure: Bronchoscopy Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study to Assess Disease Pathology and Key Therapeutic Targets in Severe Asthma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints [ Time Frame: Through 2 weeks of Prednisolone dosing ]
    biomarkers, vital signs, ECG


Secondary Outcome Measures:
  • 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. [ Time Frame: Through 2 weeks of prednisolone dosing. ]
    biomarkers


Enrollment: 47
Actual Study Start Date: August 2, 2005
Study Completion Date: June 6, 2011
Primary Completion Date: June 6, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Procedure: Bronchoscopy
All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.
Experimental: 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.
Drug: 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.
Procedure: Bronchoscopy
All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.
Experimental: 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.
Drug: 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.
Procedure: Bronchoscopy
All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.
Placebo Comparator: Healthy subjects group
Non-asthmatic and non-smokers with FEV1 > 85% predicted, on no regular medication.
Procedure: Bronchoscopy
All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.

  Eligibility

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.
  • Currently or planning to take during the study regular medication (including over-the-counter) except for medication allowed in inclusion criteria.
  • 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).

In addition, the following additional exclusion criteria must apply to mild to moderate persistent asthmatics on regular inhaled steroids:

  • 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.

In addition, the following additional exclusion criteria must apply to severe persistent asthmatics with clinical controlled asthma symptoms:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00327197


Locations
United Kingdom
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00327197     History of Changes
Other Study ID Numbers: RES100769
First Submitted: May 17, 2006
First Posted: May 18, 2006
Last Update Posted: August 4, 2017
Last Verified: August 2017

Keywords provided by GlaxoSmithKline:
bronchoscopy
Sputum induction
Prednisolone
Asthma
biomarkers

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents