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

• ClinicalTrials.gov Identifier: NCT00354354
• Recruitment Status: Completed
• First Posted: July 20, 2006
• Last Update Posted: April 19, 2011
• Sponsor: Queen's University
• Information provided by: Queen's University

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Combivent	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bronchodilator Effect on O2 Deficit and V'O2 Kinetics During Moderate Intensity Exercise in Normoxemic COPD.
• Study Start Date: March 2006
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. evaluate whether bronchodilators will accelerate, indirectly, phase 2 kinetics in COPD [ Time Frame: 2 hours post-inhalation of study drug ]
3. evaluate whether bronchodilators will shorten t for V'E, V'CO2 , and V'O2 [ Time Frame: 2 hours post-inhalation of study drug ]
4. evaluate whether bronchodilators will shorten half-times for HR and O2 pulse [ Time Frame: 2 hours post-inhalation of study drug ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Laveneziana P, Palange P, Ora J, Martolini D, O'Donnell DE. Bronchodilator effect on ventilatory, pulmonary gas exchange, and heart rate kinetics during high-intensity exercise in COPD. Eur J Appl Physiol. 2009 Dec;107(6):633-43. doi: 10.1007/s00421-009-1169-4. Epub 2009 Aug 27.

• Responsible Party: Dr. Denis O'Donnell, Queen's University
• ClinicalTrials.gov Identifier: NCT00354354
• Other Study ID Numbers: DMED-926-06
• First Posted: July 20, 2006
• Last Update Posted: April 19, 2011
• Last Verified: April 2011

Keywords provided by Queen's University:

COPD; Combivent; Exercise; Bronchodilator; Kinetics

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Ipratropium; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Antagonists; Cholinergic Agents