Clinical trial NCT01491802: Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD
Official title: A 4-week Randomized, Double-blind, Crossover Study to Assess the Effect of a New LABA/LAMA Combination Versus LAMA Alone on Exertional Dyspnea, Exercise Endurance and Neuromechanical Coupling in Patients With GOLD Stage II COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Keywords: COPD
Combination therapy
Anticholinergic
Beta2-agonist
Exercise
Dyspnea
Respiratory mechanics
Lead sponsor: Queen's University
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2011-12-14
Enrollment: 17
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Preliminary information from our laboratory indicated that even patients with milder chronic obstructive pulmonary disease (COPD) can have significant physiological derangements which become more pronounced during exercise, leading to intolerable dyspnea at lower levels of ventilation than in health. This study will explore pathophysiological mechanisms of dyspnea and activity limitation in GOLD stage II COPD and will determine if there is a sound physiological rationale for the use of dual long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) therapy (GSK573719/ GW642444 Inhalation Powder) versus LAMA alone (GSK573719) as treatment for dyspnea and exercise intolerance in this subpopulation. Objectives of this study are to determine if: 1) neuromechanical uncoupling of the respiratory system contributes to exertional dyspnea in milder COPD, and 2) treatment with LABA/LAMA improves dyspnea and exercise endurance compared with LAMA by improving neuromechanical coupling. The investigators hypothesize that: 1) dyspnea is related to excessive dynamic lung hyperinflation, tidal volume restriction and increased ratio of central respiratory neural drive to tidal volume displacement, a measure of neuromechanical uncoupling of the respiratory system, and 2) LABA/LAMA will improve dyspnea and exercise endurance, which will be explained by partial reversal of the above mechanical abnormalities. The investigators will conduct a randomized, double-blind crossover study and compare the effects of once-daily LABA/LAMA over 4-weeks with LAMA on dyspnea, exercise endurance and ventilatory mechanics in GOLD stage II COPD.


Eligibility criteria: Inclusion Criteria:

* Stable moderate COPD
* Post-bronchodilator FEV1/FVC\<0.7 and 50%≤FEV1\<80% predicted
* Baseline Dyspnea Index ≤ 9 and MRC dyspnea scale \>2
* Cigarette smoking history at least 20 pack-years

Exclusion Criteria:

* Presence of a significant disease other than COPD that could contribute to dyspnea and exercise limitation
* Important contraindications to clinical exercise testing
* Use of daytime oxygen
* History of asthma

Primary outcomes:
measure: Exertional Dyspnea Intensity at Isotime Exercise.
timeFrame: 4 weeks
Secondary outcomes:
measure: Exercise Endurance Time
timeFrame: 4 weeks
measure: Inspiratory Capacity at Rest
timeFrame: 4 weeks
measure: Ventilation at Isotime Exercise
timeFrame: 4 weeks
measure: Intensity of "Unpleasantness of Breathing" at Isotime Exercise
timeFrame: 4 weeks
measure: Inspiratory Capacity at Isotime Exercise
timeFrame: 4 weeks
measure: Diaphragm Electromyogram (EMGdi) at Isotime Exercise
timeFrame: 4 weeks
measure: Tidal Esophageal Pressure (Pes) Swings at Isotime Exercise
timeFrame: 4 weeks
measure: Mean Expiratory Flow at Isotime Exercise
timeFrame: 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: KIngston
country: Canada
facility: Respiratory Investigation Unit at Kingston General Hospital
state: Ontario
Study officials:
affiliation: Queen's University and Kingston General Hospital
name: Denis E O'Donnell, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: