Chronic Obstructive Pulmonary DiseasePhase 4NCT00354354
Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
A Phase 4 study testing Combivent in people with Chronic Obstructive Pulmonary Disease, run by Queen's University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Combivent
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2006to Jul 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 40-80 years
- stable COPD
- FEV1 < 60 % predicted
- severe chronic breathlessness (Baseline Dyspnea Index < 6)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Respiratory Investigation Unit (Queen's University)
Kingston, Ontario, K7L 2V7
About this study
Official title: Bronchodilator Effect on O2 Deficit and V'O2 Kinetics During Moderate Intensity Exercise in Normoxemic COPD.
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 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.
- 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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Combivent
- Keywords
- COPD, Combivent, Exercise, Bronchodilator, Kinetics
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CombiventDrug
Also called Ipratropium - Salbutamol
Nebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Combivent Receives: Drug: Combivent |
| 2 | Placebo comparator | Saline Solution (0.9% NaCl) Receives: Drug: Combivent |
What is being measured
The primary outcome is the main question the study is designed to answer.
effects of bronchodilators on V'E , V'CO2 , and V'O2 kinetics in COPD during constant work-rate cycle exercise.
Measured: 2 hours post-inhalation of study drug
evaluate whether bronchodilators will accelerate, indirectly, phase 2 kinetics in COPD
Measured: 2 hours post-inhalation of study drug
evaluate whether bronchodilators will shorten t for V'E, V'CO2 , and V'O2
Measured: 2 hours post-inhalation of study drug
evaluate whether bronchodilators will shorten half-times for HR and O2 pulse
Measured: 2 hours post-inhalation of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2006 (estimated)
- Study startMar 2006
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Investigators
- Denis E O'Donnell, MD, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00354354
- Sponsor's protocol ID
- DMED-926-06
- Status last verified
- Apr 2011
- First submitted
- 18 Jul 2006
- Last updated
- 19 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19711095
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bronchodilator Effect on O2 Deficit and V'O2 Kinetics During Moderate Intensity Exercise in Normoxemic COPD.
- ClinicalTrials.gov ID
- NCT00354354
- Acronym / sponsor ID
- DMED-926-06
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Combivent, Exercise, Bronchodilator, Kinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Study start
- Mar 2006
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 20 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
- 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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CombiventCombivent |
| 2 | Placebo comparator | Drug: CombiventSaline Solution (0.9% NaCl) |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 40-80 years
- stable COPD
- FEV1 < 60 % predicted
- severe chronic breathlessness (Baseline Dyspnea Index < 6)
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CombiventAlso: Ipratropium - SalbutamolNebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects. | Drug | 1, 2 |
Primary outcome
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
evaluate whether bronchodilators will accelerate, indirectly, phase 2 kinetics in COPD
Time frame: 2 hours post-inhalation of study drug
evaluate whether bronchodilators will shorten t for V'E, V'CO2 , and V'O2
Time frame: 2 hours post-inhalation of study drug
evaluate whether bronchodilators will shorten half-times for HR and O2 pulse
Time frame: 2 hours post-inhalation of study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2011.
- Derived from this study: PubMed 19711095Laveneziana 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denis E O'Donnell, MD principal investigator
Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Combivent in people with Chronic Obstructive Pulmonary Disease, run by Queen's University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00354354, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2011; AzTrials last refreshed its copy on 2 Nov 2026.