COX-2 Inhibition in Allergic Asthma

Sponsor

Barbro Dahlen (Other)

Overall Status

Completed

CT.gov ID

NCT01002690

Collaborator

Karolinska Institutet (Other)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is part of a research programme into mechanisms of asthmatic airway obstruction, focusing on the role of lipid mediators such as the prostaglandins.

To this end the effect of a non-steroidal anti-inflammatory drug, the selective COX-2 inhibitor etoricoxib, will be evaluated in the allergen challenge setting in twelve subjects with intermittent allergic asthma. Active treatment for 10 to 13 days will be compared with an identical study period with no treatment in a cross-over, randomised design. Rising dose allergen challenges will be performed on three occasions to assess possible changes in airways responsiveness. Sampling of blood, urine, saliva and sputum will be done to allow for analyses of the production of prostaglandins and other lipid mediators, of the efficacy of COX-2 inhibition as well as of regulation of immune cells.

It is hypothesized that inhibition of COX-2 by virtue of inhibition of bronchoprotective prostaglandin E2 leads to a slightly exaggerated airway response to allergen exposure.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Etoricoxib	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effect of COX-2 Inhibition on Allergen-induced Airway Obstruction in Subjects With Asthma

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etoricoxib 10-13 days treatment with etoricoxib	Drug: Etoricoxib 90 mg/day orally for 10-13 days Other Names: Arcoxia

Arm

Intervention/Treatment

Experimental: Etoricoxib

10-13 days treatment with etoricoxib

Drug: Etoricoxib

90 mg/day orally for 10-13 days

Other Names:

Arcoxia

Outcome Measures

Primary Outcome Measures

Allergen PD20 FEV1 [10 to 13 days]

Secondary Outcome Measures

Urinary prostaglandin E2 and D2 concentrations [10-13 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Female or male aged 18 to 55 years inclusive
A history of asthma for at least 6 months with at least one of the following:
response to standard asthma treatment
episodic wheezing
change in lung function over short periods of time
A positive methacholine challenge test as evidenced by a PD20 ≤7256 µg cumulated dose within 8 weeks prior to screening or at the screening visit.
Stable intermittent asthma, only using bronchodilator therapy as needed for the last 4 weeks.
FEV1 ≥ 75% of predicted.
A positive skin prick test to pollen (grass, birch, mugwort) or animal dander (dog, cat)

Exclusion Criteria:

Known or suspected hypersensitivity to coxibs
Any significant respiratory disease other than asthma
Respiratory tract infection within 4 weeks before inclusion.
Any significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study. In particular previous or present history of cardiovascular disease, ie myocardial infarction, stroke, severe hypertension, left ventricular heart failure and/or pulmonary hypertension are strict exclusion criteria.
Current or former smoker within the last year and a smoking history of >4 packyears
Pregnancy/breastfeeding
Use of:
inhaled glucocorticosteroid treatment or use of oral corticosteroids for the last 8 weeks prior to inclusion or during the study.
inhaled long-acting or oral beta2-agonists, anticholinergic bronchodilators, cromones, antihistamines, theophyllines and antileukotrienes within 2 weeks of screening or during the study.
paracetamol, NSAIDs or any other antiinflammatory drugs the last 2 weeks prior to inclusion or during the study.
need of any other regular drug treatment that may interfere with the study outcomes.
BMI >30 kg/m2.
Use of any beta-blocking agent
Any non-asthma-related, clinically significant abnormal finding in physical and/or vital signs, and/or in hematology or blood chemistry tests at visit 1, which in the opinion of the investigator, may put the patient at risk because of participation in the study.