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

This study is currently recruiting participants.
Verified April 2014 by Queen's University
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Dr. Denis O'Donnell, Queen's University
ClinicalTrials.gov Identifier:
NCT01491802
First received: December 12, 2011
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
COPD
Drug: GSK573719/GW642444
Drug: GSK573719
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Queen's University:

Primary Outcome Measures:
  • Exertional dyspnea intensity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Intensity rating (modified 10-point Borg scale) at a standardized time during exercise


Secondary Outcome Measures:
  • Exercise endurance time [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Duration of constant work rate cycle exercise at 75% of maximum

  • Pulmonary function tests [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Comprehensive measurements of pulmonary function

  • Cardiopulmonary exercise measurements [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Measurements during constant work rate exercise will include: ventilation, breathing pattern, operating lung volumes, respiratory mechanics, diaphragm electromyogram (EMG)


Estimated Enrollment: 24
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LAMA component
GSK573719 is a long-acting muscarinic antagonist
Drug: GSK573719
GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
Experimental: LABA/LAMA combination
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.
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.
Other Names:
  • GSK573719+GW642444
  • Vilanterol (GW642444)

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01491802

Contacts
Contact: Katherine A Webb, M.Sc. 613-549-6666 ext 4950 kw2@queensu.ca

Locations
Canada, Ontario
Respiratory Investigation Unit at Kingston General Hospital Recruiting
KIngston, Ontario, Canada, K7L 2V7
Contact: Katherine A Webb, M.Sc.    613-549-6666 ext 4950    kw2@queensu.ca   
Principal Investigator: Denis E O'Donnell, MD, FRCPC         
Sponsors and Collaborators
Queen's University
GlaxoSmithKline
Investigators
Principal Investigator: Denis E O'Donnell, MD, FRCPC Queen's University and Kingston General Hospital
  More Information

No publications provided

Responsible Party: Dr. Denis O'Donnell, Principal Investigator, Queen's University
ClinicalTrials.gov Identifier: NCT01491802     History of Changes
Other Study ID Numbers: DMED-1426-11
Study First Received: December 12, 2011
Last Updated: April 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by Queen's University:
COPD
Combination therapy
Anticholinergic
Beta2-agonist
Exercise
Dyspnea
Respiratory mechanics

Additional relevant MeSH terms:
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014