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

COPD Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01491802
• Other study ID #: DMED-1426-11
• Status: Completed
• Phase: Phase 3
• First received: December 12, 2011
• Last updated: November 7, 2014
• Start date: January 2012
• Est. completion date: September 2014

Study information

• Verified date: November 2014
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• COPD

Intervention

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

Locations

Country	Name	City	State
Canada	Respiratory Investigation Unit at Kingston General Hospital	KIngston	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Queen's University	GlaxoSmithKline

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exertional dyspnea intensity	Intensity rating (modified 10-point Borg scale) at a standardized time during exercise	4 weeks	No
Secondary	Exercise endurance time	Duration of constant work rate cycle exercise at 75% of maximum	4 weeks	No
Secondary	Pulmonary function tests	Comprehensive measurements of pulmonary function	4 weeks	No
Secondary	Cardiopulmonary exercise measurements	Measurements during constant work rate exercise will include: ventilation, breathing pattern, operating lung volumes, respiratory mechanics, diaphragm electromyogram (EMG)	4 weeks	No