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Completed

NCT Number: NCT01491802

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

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.

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Key information

Conditions

COPD Behavior Chronic Disease Disease Attributes Dyspnea Lung Diseases Lung Diseases, Obstructive Motor Activity Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiration Disorders Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Respiratory Investigation Unit at Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LAMA/LABA

Drug

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, umeclidinium (GSK573719) / vilanterol (GW642444), Anoro ELLIPTA

LAMA

Drug

GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks

Other names: umeclidinium

Primary outcomes

  1. Exertional Dyspnea Intensity at Isotime Exercise.

    Time frame: 4 weeks

    Intensity of dyspnea (defined as breathing discomfort) at a standardized time (isotime) during constant work rate exercise tests as measured by the modified 10-point Borg scale. A rating of 0 represents no dyspnea up to a maximum of 10: a smaller rating is therefore an improvement. Isotime was defined as the highest exercise time in minutes completed in both post-treatment tests.

Secondary outcomes

  1. Exercise Endurance Time

    Time frame: 4 weeks

    Duration of constant work rate cycle exercise at 75% of maximum

  2. Inspiratory Capacity at Rest

    Time frame: 4 weeks

    Measurements of pulmonary function included spirometry and body plethysmography. The resting inspiratory capacity (IC) values reported here are 90 minutes post-dose after 4 weeks of treatment.

  3. Ventilation at Isotime Exercise

    Time frame: 4 weeks

    Ventilation was measured during constant work rate exercise tests. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.

  4. Intensity of "Unpleasantness of Breathing" at Isotime Exercise

    Time frame: 4 weeks

    Intensity rating (modified 10-point Borg scale) measured at a standardized time (isotime) during constant work rate exercise tests. A rating of 0 represents no "unpleasantness of breathing" up to a maximum of 10. An improvement would be noted as a decrease in the Borg scale rating. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.

  5. Inspiratory Capacity at Isotime Exercise

    Time frame: 4 weeks

    Measurements of inspiratory capacity (IC) were conducted during constant work rate exercise tests. Isotime was defined as the highest time in minutes completed in both post-treatment tests.

  6. Diaphragm Electromyogram (EMGdi) at Isotime Exercise

    Time frame: 4 weeks

    EMGdi was measured during constant work rate exercise tests via a multipair-electrode esophageal catheter. EMGdi expressed as a percentage of its maximum is used as an index of inspiratory neural drive. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.

  7. Tidal Esophageal Pressure (Pes) Swings at Isotime Exercise

    Time frame: 4 weeks

    Tidal esophageal pressure (Pes) swings were measured via an esophageal balloon catheter during constant work rate exercise tests. Tidal Pes expressed relative to maximum is an index of respiratory effort. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.

  8. Mean Expiratory Flow at Isotime Exercise

    Time frame: 4 weeks

    Mean expiratory flow was measured during constant work rate exercise tests. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.

  9. Forced Expiratory Volume in 1 Second (FEV1)

    Time frame: 4 weeks

    Measurements of pulmonary function included spirometry and body plethysmography. Values reported are 90 minutes post-dose after 4 weeks of treatment.

Sponsors and collaborators

Lead sponsor

Queen's University

Other

Collaborators

  • GlaxoSmithKline

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Dec 14, 2011
Registry last updated
Aug 15, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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