- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01491802
Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD
May 2, 2017 updated by: Dr. Denis O'Donnell, Queen's University
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
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
-
KIngston, Ontario, Canada, K7L 2V7
- Respiratory Investigation Unit at Kingston General Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
38 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LAMA alone, then LAMA/LABA combination
Participants will first receive an inhaled long-acting muscarinic antagonist (LAMA) once daily for 4 weeks.
After a 2 week washout period, they will then receive the fixed-dose combination product [LAMA plus long-acting beta2-agonist (LABA)] once daily for 4 weeks.
|
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 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
Other Names:
|
Experimental: LABA/LAMA combination, then LAMA alone
Participants will first receive a long-acting muscarinic antagonist (LAMA) plus long-acting beta2-agonist (LABA) combination product once daily for 4 weeks.
After a 2 week washout period, they will then receive the LAMA single product once daily for 4 weeks.
|
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 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exercise Endurance Time
Time Frame: 4 weeks
|
Duration of constant work rate cycle exercise at 75% of maximum
|
4 weeks
|
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.
|
4 weeks
|
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 weeks
|
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.
|
4 weeks
|
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.
|
4 weeks
|
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.
|
4 weeks
|
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.
|
4 weeks
|
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.
|
4 weeks
|
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.
|
4 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Denis E O'Donnell, MD, FRCPC, Queen's University and Kingston General Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2012
Primary Completion (Actual)
September 1, 2014
Study Completion (Actual)
September 1, 2014
Study Registration Dates
First Submitted
December 12, 2011
First Submitted That Met QC Criteria
December 13, 2011
First Posted (Estimate)
December 14, 2011
Study Record Updates
Last Update Posted (Actual)
August 15, 2017
Last Update Submitted That Met QC Criteria
May 2, 2017
Last Verified
May 1, 2017
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- DMED-1426-11
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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