Ignite Creation Date:
2024-05-05 @ 5:14 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00412204
Status:
COMPLETED
Last Update Posted:
2009-10-21
First Post:
2006-12-14
Brief Title:
Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease COPD During Exercise
Sponsor:
McMaster University
Organization:
McMaster University
Study Overview
Official Title:
A Double-blind Placebo-controlled Crossover Study to Evaluate the Effects of Tiotropium Bromide on Gas Exchange in Subjects With COPD During Exercise
Status:
COMPLETED
Status Verified Date:
2009-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine the effect of treatment with tiotropium bromide on efficiency of gas exchange and exercise performance in COPD subjects during exercise
Detailed Description:
This study will investigate the effect of tiotropium on gas exchange during exercise In addition we hypothesize that bronchodilation by tiotropium will open functional lung units improving gas exchange in subjects with COPD While other studies have shown that tiotropium improves exertional dyspnea and exercise tolerance and reduces resistive and elastic work in subjects with COPD there have been no investigations of the effects of anti-cholinergic bronchodilation on gas exchange This study will confirm and extend earlier observations on exertional dyspnea and exercise tolerance
Efficiency of gas exchange will be evaluated through assessments of metabolic demand VO2 cardiac output Q ventilation V in overall terms ie QVO2 VVO2
Improved efficiency of gas exchange will reduce the ventilatory demand for a given workload providing an alternate mechanism for the observed improvement in exertional dyspnea and exercise tolerance in subjects with COPD The overall ventilation required to meet metabolic demands is dependent on the alveolar volume which can be easily measured using inert gases This is conveniently measured during the DLco maneuver which will be measured In general ventilation increases with metabolic demand but increases progressively as the VA and KCO decline in patients with COPD These factors may be amenable to improvement using anticholinergic agents In addition the recruitment of additional alveolar volume provides an additional pathway for blood flow through the lung increasing overall cardiac output and enhancing the responsiveness of peripheral muscle in these patients These have not been considered and exploited as potential therapeutic goals
Study Evaluations
Treatment Period Visits 2 3 5 and 6
Vital signs seated
12 lead ECG
Medication washout compliance
Stage one exercise test refer to section 1117
Randomization will occur at Visit 2
At visit two the subject will be trained in the use of a HandiHaler
Study medication will be dispensed at Visit 2 and 5
Administer study medication Visits 2345 and 6
Treatment Period Visits 4 and 7
Vital signs seated
Administer study medication
Constant load exercise test refer to section 1118
Collect study medication
Medication accountability
Adverse event A follow up visit must be scheduled if there are any ongoing AEs at visit 7
Follow up Visit within 30 days of visit 7
This visit will take place only if clinically significant abnormalities are seen after all results from Visit 7 are obtained and reviewed by the Investigator and Medical Monitor
After informed consent patients will attend an initial screening visit Visit 1 for review of medical history clinical assessment complete pulmonary function testing plethysmography and spirometry A symptom-limited incremental cycle exercise test with measurement of incremental and peak VO2 carbon dioxide output VCO2 minute ventilation Ve Vt respiratory frequency heart rate HR oxyhemoglobin saturation by pulse oximeter SpO2 and modified Borg score for breathlessness will also be performed at screening as well as measurements of airway responses to salbutamol
Patients who meet the eligibility requirements will be randomized to treatment with tiotropium or placebo Double-blind medication will be dispensed in HandiHalers to be taken once daily in the morning for 22 days Patients will report to the laboratory for two separate treatment periods with a washout of 4-6 weeks between treatment periods A patient diary card will be kept to document morning doses of study medication for calculation of compliance The patient will return used medication capsules for confirmation of medication compliance Safety will be assessed by examining adverse events AEs resting and exercise electro cardio grams ECGs routine laboratory tests and vital signs
In the event of treatment of an exacerbation with oral corticosteroids any scheduled visit will be delayed for 1 week following the last dose of steroid treatment
Efficiency of gas exchange will be evaluated through assessments of metabolic demand VO2 cardiac output Q ventilation V in overall terms ie QVO2 VVO2
Improved efficiency of gas exchange will reduce the ventilatory demand for a given workload providing an alternate mechanism for the observed improvement in exertional dyspnea and exercise tolerance in subjects with COPD The overall ventilation required to meet metabolic demands is dependent on the alveolar volume which can be easily measured using inert gases This is conveniently measured during the DLco maneuver which will be measured In general ventilation increases with metabolic demand but increases progressively as the VA and KCO decline in patients with COPD These factors may be amenable to improvement using anticholinergic agents In addition the recruitment of additional alveolar volume provides an additional pathway for blood flow through the lung increasing overall cardiac output and enhancing the responsiveness of peripheral muscle in these patients These have not been considered and exploited as potential therapeutic goals
Study Evaluations
Treatment Period Visits 2 3 5 and 6
Vital signs seated
12 lead ECG
Medication washout compliance
Stage one exercise test refer to section 1117
Randomization will occur at Visit 2
At visit two the subject will be trained in the use of a HandiHaler
Study medication will be dispensed at Visit 2 and 5
Administer study medication Visits 2345 and 6
Treatment Period Visits 4 and 7
Vital signs seated
Administer study medication
Constant load exercise test refer to section 1118
Collect study medication
Medication accountability
Adverse event A follow up visit must be scheduled if there are any ongoing AEs at visit 7
Follow up Visit within 30 days of visit 7
This visit will take place only if clinically significant abnormalities are seen after all results from Visit 7 are obtained and reviewed by the Investigator and Medical Monitor
After informed consent patients will attend an initial screening visit Visit 1 for review of medical history clinical assessment complete pulmonary function testing plethysmography and spirometry A symptom-limited incremental cycle exercise test with measurement of incremental and peak VO2 carbon dioxide output VCO2 minute ventilation Ve Vt respiratory frequency heart rate HR oxyhemoglobin saturation by pulse oximeter SpO2 and modified Borg score for breathlessness will also be performed at screening as well as measurements of airway responses to salbutamol
Patients who meet the eligibility requirements will be randomized to treatment with tiotropium or placebo Double-blind medication will be dispensed in HandiHalers to be taken once daily in the morning for 22 days Patients will report to the laboratory for two separate treatment periods with a washout of 4-6 weeks between treatment periods A patient diary card will be kept to document morning doses of study medication for calculation of compliance The patient will return used medication capsules for confirmation of medication compliance Safety will be assessed by examining adverse events AEs resting and exercise electro cardio grams ECGs routine laboratory tests and vital signs
In the event of treatment of an exacerbation with oral corticosteroids any scheduled visit will be delayed for 1 week following the last dose of steroid treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None