Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD
Condition: COPD
Intervention: LAMA/LABA; LAMA
Intervention description: 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 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 17.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: COPD; Combination therapy; Anticholinergic; Beta2-agonist; Exercise; Dyspnea; Respiratory mechanics

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.
    

Eligibility criteria:

        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