Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients - Full Text View

Sponsored by:	Queen's University
Information provided by:	Queen's University
ClinicalTrials.gov Identifier:	NCT00354354

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:

To compare V'E, V'CO2, and V'O2 kinetics in COPD and age-matched healthy individuals during constant work-rate cycle exercise at 80% of AT V'O2 .
To evaluate the effects of a bronchodilators on V'E , V'CO2 , and V'O2 kinetics in COPD and age-matched healthy individuals 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.
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 IV

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease) Exercise and Physical Fitness

Drug Information available for: Sodium chloride Albuterol sulfate Albuterol Levalbuterol hydrochloride Levalbuterol tartrate Ipratropium Ipratropium bromide

U.S. FDA Resources

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

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 and age-matched healthy individuals 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 and age-matched healthy individuals . [ 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 in COPD and age-matched healthy individuals . [ 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 in COPD and age-matched healthy individuals . [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

V'E at 80% Anaerobic Threshold of constant workload (COPD vs healthy normal). [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
V'CO2 80% Anaerobic Threshold of constant workload(COPD vs healthy normal). [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
V'O2 kinetics 80% Anaerobic Threshold of constant workload(COPD vs healthy normal). [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
hyperinflation (COPD vs healthy normal) during treatments. [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
cardiovascular and pulmonary function(COPD vs healthy normal)during treatments. [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]
exercise limitation noted during treatments (COPD vs healthy normal). [ Time Frame: 2 hours post-inhalation of study drug ] [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	March 2006
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Combivent	Drug: Combivent Nebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects.
2: Placebo Comparator 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.

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:	Yes

Criteria

Inclusion Criteria:

COPD:

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

Healthy:

40-80 years
stable
normal baseline spirometry (FEV1 ≥ 80% predicted, FEV1/FVC ratio ≥ 70 %)
free of any health problems which may contribute to dyspnea or exercise limitation.

Exclusion Criteria:

COPD:

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.

Healthy:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354354

Contacts

Contact: Pierantonio Lavenenziana, MD	(613) 549-6666 ext 4332	pier_lav@yahoo.it
Contact: Kathy A Webb, M.Sc.	(613) 549-6666 ext 4950	kathy.webb@queensu.ca

Locations

Canada, Ontario
Respiratory Investigation Unit (Queen's University)	Recruiting
Kingston, Ontario, Canada, K7L 2V7
Contact: Kathy A Webb, M.Sc. 613-549-6666 ext 4950 kathy.webb@queensu.ca

Sponsors and Collaborators

Queen's University

Investigators

Principal Investigator:

Denis E O'Donnell, MD

Queen's University

More Information

Responsible Party:	Queen's University ( Dr. Denis O'Donnell )
Study ID Numbers:	DMED-926-06
Study First Received:	July 18, 2006
Last Updated:	August 25, 2008
ClinicalTrials.gov Identifier:	NCT00354354
Health Authority:	Canada: Health Canada

Keywords provided by Queen's University:

Chronic
Obstructive
Pulmonary Disease
COPD
Combivent

Exercise
Bronchodilator
Oxygen
Kinetics

Study placed in the following topic categories:

Lung Diseases, Obstructive
Ipratropium
Respiratory Tract Diseases
Lung Diseases

Albuterol
Respiration Disorders
Pulmonary Disease, Chronic Obstructive

ClinicalTrials.gov processed this record on January 14, 2009