COX-2 Inhibition in Allergic Asthma

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Etoricoxib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, SE-141 86
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Allergen PD20 FEV1	10 to 13 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Urinary prostaglandin E2 and D2 concentrations	10-13 days

Collaborators and Investigators

• Sponsor: Barbro Dahlen
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Barbro Dahlén, MD PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: October 26, 2009
• First Submitted That Met QC Criteria: October 26, 2009
• First Posted (ESTIMATE): October 27, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2013
• Last Update Submitted That Met QC Criteria: April 23, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Asthma; Allergen challenge; Airway responsiveness; Eicosanoids; Prostaglandins
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Etoricoxib
• Other Study ID Numbers: COX2EAR090531