Clinical trial NCT00327197: Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma
Official title: A Study to Assess Disease Pathology and Key Therapeutic Targets in Severe Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Asthma
Keywords: bronchoscopy
Sputum induction
Prednisolone
Asthma
biomarkers
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-05-18
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

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.

Primary outcomes:
measure: Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints
timeFrame: Through 2 weeks of Prednisolone dosing
Secondary outcomes:
measure: 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.
timeFrame: Through 2 weeks of prednisolone dosing.
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
state: Leicestershire
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.