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Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD

This study has been completed.
Information provided by (Responsible Party):
Dr. Denis O'Donnell, Queen's University Identifier:
First received: December 12, 2011
Last updated: November 7, 2014
Last verified: November 2014
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.

Condition Intervention Phase
COPD Drug: GSK573719/GW642444 Drug: GSK573719 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Dr. Denis O'Donnell, Queen's University:

Primary Outcome Measures:
  • Exertional dyspnea intensity [ Time Frame: 4 weeks ]
    Intensity rating (modified 10-point Borg scale) at a standardized time during exercise

Secondary Outcome Measures:
  • Exercise endurance time [ Time Frame: 4 weeks ]
    Duration of constant work rate cycle exercise at 75% of maximum

  • Pulmonary function tests [ Time Frame: 4 weeks ]
    Comprehensive measurements of pulmonary function

  • Cardiopulmonary exercise measurements [ Time Frame: 4 weeks ]
    Measurements during constant work rate exercise will include: ventilation, breathing pattern, operating lung volumes, respiratory mechanics, diaphragm electromyogram (EMG)

Enrollment: 17
Study Start Date: January 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LAMA component
GSK573719 is a long-acting muscarinic antagonist
Drug: GSK573719
GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
Experimental: LABA/LAMA combination
GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy.
Drug: GSK573719/GW642444
GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks.
Other Names:
  • GSK573719+GW642444
  • Vilanterol (GW642444)


Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01491802

Canada, Ontario
Respiratory Investigation Unit at Kingston General Hospital
KIngston, Ontario, Canada, K7L 2V7
Sponsors and Collaborators
Queen's University
Principal Investigator: Denis E O'Donnell, MD, FRCPC Queen's University and Kingston General Hospital
  More Information

Responsible Party: Dr. Denis O'Donnell, Principal Investigator, Queen's University Identifier: NCT01491802     History of Changes
Other Study ID Numbers: DMED-1426-11
Study First Received: December 12, 2011
Last Updated: November 7, 2014

Keywords provided by Dr. Denis O'Donnell, Queen's University:
Combination therapy
Respiratory mechanics

Additional relevant MeSH terms:
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on July 21, 2017