Mechanisms of Adverse Effects of Long-Acting Beta-Agonists in Asthma

• Status: Not yet recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to elucidate the pathophysiological mechanisms underlying the adverse effects associated with the use of long-acting beta-agonists (LABAs) in asthma. Participants with mild asthma will be enrolled into a single-arm, unblinded trial in which they receive 2 weeks of salmeterol xinafoate monotherapy, followed by a 2-week washout period, followed by 2 weeks of salmeterol xinafoate / fluticasone propionate combination therapy. The induction of asthma disease-relevant pro-inflammatory mediators in the airways will be measured at each stage and correlated with relevant clinical parameters.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Collaborator: European Research Council
• Treatments: Fluticasone; Fluticasone-Salmeterol Drug Combination; Salmeterol Xinafoate

Criteria

INCLUSION CRITERIA

• Age > 18 years

• A doctor's diagnosis of asthma (mild in severity)

• No current regular asthma treatment or regular asthma treatment in the preceding 6 weeks; only a history of using short-acting bronchodilator inhalers on demand is allowed

• Pre-bronchodilator FEV1 value > 80% of the predicted value

EXCLUSION CRITERIA

• History or evidence of chronic respiratory disease other than asthma

• History or evidence of other disease, blood test results outside the normal reference range or medication use that would impair the ability of participants to safely undertake the study or the ability of researchers to interpret the study results; this includes, but is not limited to, the use of anticoagulants (e.g. warfarin), adenosine diphosphate (ADP) receptor inhibitors (e.g. clopidogrel), antiretroviral therapy (due to the potential for interaction with fluticasone), certain antifungal agents (due to the potential for interaction with fluticasone) and beta-blockers

• Current use or use in the last 6 weeks of systemic or nasal topical steroids, inhaled corticosteroids or systemic immunosuppressants

• Platelet count < 150 x 109/L or international normalised ratio (INR) > 1.5

• History of smoking > 5 pack years, current smoker or history of smoking in the last 4 weeks

• Current vaping or history of vaping in the last 4 weeks

• Current illicit drug use/abuse

• Abnormal chest x-ray appearance

• Signs or symptoms of upper respiratory tract infection or lower respiratory tract infection in the preceding 6 weeks

• Cardiac conduction abnormalities on electrocardiogram (ECG)

• Current pregnancy or planning to become pregnant during the study period

• Breastfeeding during the study period

• Inability to provide informed consent to participate in the study

• Current involvement in any other clinical research studies involving medicinal products or devices; or involvement in clinical research studies involving medicinal products within the last 30 days or within 5 half-lives of the medicinal product (whichever is longer)

• Inability to speak English or inability to understand verbal or written English

• Inability to attend hospital for all scheduled study visits

• Hypersensitivity to any of the investigational medicinal products (IMPs) or their excipients