Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients

This study has been completed.
Sponsor:
Information provided by:
Queen's University
ClinicalTrials.gov Identifier:
NCT00354354
First received: July 18, 2006
Last updated: April 18, 2011
Last verified: April 2011
  Purpose

Hypothesis: The reduction of dynamic hyperinflation and its negative effects on the respiratory system following a bronchodilator could lead to an improvement of cardiac function in terms of increased cardiac output. This may enhance oxygen delivery to the exercising muscles in COPD patients. Bronchodilator administration may also have an indirect effect on V'O2 kinetics via its action on cardiovascular and pulmonary variables.

Objectives:

  1. To evaluate the effects of a bronchodilators on V'E , V'CO2 , and V'O2 kinetics in COPD during constant work-rate cycle exercise, and to evaluate whether bronchodilators will accelerate, indirectly, phase 2 kinetics (usually slower in COPD patients than normal subjects) and shorten t for V'E, V'CO2 , and V'O2 and shorten half-times for HR and O2 pulse, thus showing an improvement of oxygen transport to the peripheral active muscles.
  2. To determine the impact of a bronchodilator-induced reduction in dynamic hyperinflation, and its effects on cardiovascular and pulmonary function, on exercise limitation in COPD.

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Combivent
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Bronchodilator Effect on O2 Deficit and V'O2 Kinetics During Moderate Intensity Exercise in Normoxemic COPD.

Resource links provided by NLM:


Further study details as provided by Queen's University:

Primary Outcome Measures:
  • effects of bronchodilators on V'E , V'CO2 , and V'O2 kinetics in COPD during constant work-rate cycle exercise. [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
  • evaluate whether bronchodilators will accelerate, indirectly, phase 2 kinetics in COPD [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
  • evaluate whether bronchodilators will shorten t for V'E, V'CO2 , and V'O2 [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
  • evaluate whether bronchodilators will shorten half-times for HR and O2 pulse [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: March 2006
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Combivent
Drug: Combivent
Nebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects.
Other Name: Ipratropium - Salbutamol
Placebo Comparator: 2
Saline Solution (0.9% NaCl)
Drug: Combivent
Nebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects.
Other Name: Ipratropium - Salbutamol

Detailed Description:

The inability to engage in the usual activities of daily living is one of the most distressing experiences of people afflicted with Chronic Obstructive Pulmonary Disease (COPD). Exercise intolerance progresses relentlessly as the disease advances and can lead to virtual immobility and social isolation. Our understanding of the complex interface between physiological impairment and disability in COPD has increased considerably in recent years. It has become clear that in COPD, exercise intolerance ultimately reflects integrated abnormalities of the ventilatory, cardiovascular, peripheral muscle and neurosensory systems. Ventilatory constraint is the dominant contributor to exercise limitation in more advanced disease. Recently, important studies have been conducted on the role of peripheral muscle dysfunction in exercise limitation in COPD.

The present study will test the hypothesis that the administration of bronchodilators (i.e., inhaled β2-agonist and inhaled anticholinergics in combination) in normoxemic COPD patients during moderate-intensity constant-load exercise may result in an enhancement of oxidative metabolism, reflected by reductions of O2 def and phase 2 tV'O2.

Fifteen normoxemic patients with stable COPD (FEV1 less than 60 % predicted) and severe chronic breathlessness (Baseline Dyspnea Index less than 6) will complete the study.

Each patient will perform three visits. At the first visit, patients will be familiarized with the various questionnaires and scales for rating the intensity and quality of symptoms and they will carry out pulmonary function testing and a symptom-limited incremental cycle exercise test in order to determine the anaerobic threshold (AT), the peak work-rate and the peak oxygen uptake. Each patient will subsequently complete two visits in which they will receive either nebulized bronchodilator (BD) (Combivent®, ipratropium 0.5 mg + salbutamol 2.5 mg) or placebo (PL), in random order. At 90-100 minutes post-dose, patients will perform pulmonary function tests, then they will perform a constant-load exercise test at 80% of AT V'O2. During constant-load exercise tests (2nd and 3rd visit), small samples of blood from the earlobe of each subject will be collected in order to determine the level of lactate and breathing gases (oxygen and carbon dioxide) in the blood.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 40-80 years
  • stable COPD
  • FEV1 < 60 % predicted
  • severe chronic breathlessness (Baseline Dyspnea Index < 6)

Exclusion Criteria:

  • SpO2 at rest < 90% or a a sustained decrease of > 4% in arterial O2 saturation during the ergometer test, as determined by pulse oximetry
  • a body mass index (BMI) < 19 or > 30
  • chronic oral steroid therapy
  • other medical conditions which could cause or contribute to breathlessness, i.e., heart disease or other respiratory diseases
  • other problem which could interfere with carrying out of exercise testing, i.e., neuromuscular diseases, orthopedic diseases, etc.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00354354

Locations
Canada, Ontario
Respiratory Investigation Unit (Queen's University)
Kingston, Ontario, Canada, K7L 2V7
Sponsors and Collaborators
Queen's University
Investigators
Principal Investigator: Denis E O'Donnell, MD Queen's University
  More Information

No publications provided by Queen's University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Denis O'Donnell, Queen's University
ClinicalTrials.gov Identifier: NCT00354354     History of Changes
Other Study ID Numbers: DMED-926-06
Study First Received: July 18, 2006
Last Updated: April 18, 2011
Health Authority: Canada: Health Canada

Keywords provided by Queen's University:
COPD
Combivent
Exercise
Bronchodilator
Kinetics

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 10, 2014