The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers
- Conditions
- Smoking
- Interventions
- Registration Number
- NCT03104634
- Lead Sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Brief Summary
This short-term study aims to prove the potential cardio-protective physiological effect of inhaled aclidinium bromide/formoterol fumarate on inspiratory pleural pressures.
Smoking is associated with gas-trapping (hyperinflation), even in the absence of chronic obstructive pulmonary disease. Breathing in the presence of gas-trapping requires large negative inspiratory pleural pressures, which are transmitted to the surface of the heart and increase cardiac wall stress.
Inhaled aclidinium bromide and formoterol fumarate has been shown to reduce gas-trapping, but the impact on inspiratory pleural pressures and biomarkers of cardiac stress in smokers is unknown.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
- Current and former smokers with ≥20 pack-years of smoking history
- Gas-trapping (residual volume >110% predicted)
Physician-diagnosis of chronic obstructive pulmonary disease in the past 1 year and regular use of long-acting antimuscarinic (LAMA) and/or long-acting beta-agonist (LABA) (i.e., at least 30 consecutive days)
- Physician-diagnosis of asthma in the past 5 years
- Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days)
- Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy
- Respiratory tract infection within 4-weeks
- Physician-diagnosis of arrhythmia, or significant valvular disease.
- Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months.
- Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram.
- Inability to use study inhaler
- Glaucoma
- Benign prostatic hypertrophy
- Pregnancy
- Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria)
- Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
- Inability to provide written informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Active arm Aclidinium bromide/formoterol fumarate dihydrate Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days Placebo arm Placebo Placebo Twice daily (once in the morning, once in the evening) 7-days
- Primary Outcome Measures
Name Time Method Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O) After 7-days of active or placebo drug Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise
- Secondary Outcome Measures
Name Time Method Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume) After 7-days of active or placebo drug Static and operating lung volumes
Effect modification by hypertension status (Joint National Committee criteria). After 7-days of active or placebo drug Interaction term added to regression model for hypertension status.
Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration) After 7-days of active or placebo drug Mean difference in atrial natriuretic peptide (exercise induced-changes) and n-terminal pro-B-type natriuretic peptide (resting).
Effect modification by gender (self-reported). After 7-days of active or placebo drug Interaction term added to regression model for gender.
Effect modification by smoking status (self-reported). After 7-days of active or placebo drug Interaction term added to regression model for smoking status.
Effect modification by hyperinflation severity (Residual lung volume). After 7-days of active or placebo drug Interaction term added to regression model for hyperinflation severity.
Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7). After 7-days of active or placebo drug Interaction term added to regression model for spirometric COPD status.
Trial Locations
- Locations (1)
McGill University Health Centre Research Institute
🇨🇦Montreal, Quebec, Canada