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

Queen's University

Status and phase: Completed; Phase 3

Conditions: COPD

Treatments: Drug: LAMA; Drug: LAMA/LABA

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01491802

DMED-1426-11

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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17 participants in 2 patient groups

LAMA alone, then LAMA/LABA combination

Experimental group

Description:

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.

Treatment:

Drug: LAMA/LABA

Drug: LAMA

LABA/LAMA combination, then LAMA alone

Experimental group

Description:

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.

Treatment:

Drug: LAMA/LABA

Drug: LAMA