Chronic Obstructive Pulmonary Disease
Conditions
Keywords
exercise;, treadmill;, cycle ergometer;, breathlessness;, leg discomfort
Brief summary
Previous studies suggest that treadmill exercise may be a more relevant exercise stimulus than the cycle ergometer to demonstrate benefits with bronchodilator therapy in patients with COPD. The hypothesis of the study is that patients with COPD will exhibit greater improvements in exercise endurance and breathlessness with arformoterol compared with normal saline during treadmill walking than with cycle exercise.
Detailed description
The study is a randomized trial with crossover of consecutively recruited patients with symptomatic COPD. Each patient will participate in seven visits over a 3-4 week period. At the first visit patients will provide informed consent and then be familiarized with equipment and testing protocols. At visits 2 and 3 patients will inhale 2 puffs of albuterol HFA MDI, and then perform symptom limited incremental exercise on the treadmill or cycle ergometer (randomized order); after a one hour rest, the patient will perform constant work exercise at 80-85% of peak VO2 on the same exercise mode. At visits 4 - 7, patients will perform PFTs at baseline and at 30 and 120 minutes after inhaling arformoterol or normal saline (randomized order) and then constant work exercise on the treadmill or cycle ergometer (randomized order). Metabolic measurements will be made throughout exercise, and patients will provide continuous ratings of breathlessness and leg discomfort using a system consisting of a computer, monitor, and a mouse.
Interventions
DRUGArformoterol tartrate
15 mcg in two ml solution administered via nebulizer
Normal saline was nebulized.
OTHERTreadmill Exercise
OTHERCycle Exercise
Sponsors
Sumitomo Pharma America, Inc.
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* male or female patient 50 years of age or older; diagnosis of COPD; current or ex-smoker with at least 10 pack-years of smoking; a patient-reported score for breathlessness during activities of daily living of \< 9 on the self-administered computerized baseline dyspnea index; a post-bronchodilator FEV1 \< 80% predicted; a post-bronchodilator FEV1/FVC ratio \< 70%; and clinically stable condition.
Exclusion criteria
* any concomitant disease that interferes with study procedures or evaluation; inability to exercise on the treadmill or cycle ergometer; inability to withhold short-acting bronchodilators for 4 hours or long-acting bronchodilators for 12 hrs (salmeterol or formoterol) and for 24 hours (tiotropium) prior to testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Endurance Time | After one dose | Participants were asked to exercise until symptom limitation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise | After one dose | linear regression slope of breathlessness - time for arformoterol and for normal saline will be compared between treadmill and cycle exercise The higher the number the worse the shortness of breath |
Countries
United States
Participant flow
Recruitment details
Participants recruited from a specialty clinic in Lebanon, NH, between August 1, 2008 to May 1, 2009.
Pre-assignment details
27 particpants recruited; 27 particpants screened; 5 excluded because they did not meet inclusion criteria; 2 patients withdrew consent after visit 1.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All 20 participants were randomized to receive all 4 of the interventions in a randomzied sequence. The 4 interventions follow:
Treadmill exercise-Arformoterol Treadmill exercise-Normal Saline Cycle exercise-Arformoterol Cycle exercise-Normal Saline | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age Continuous | 64 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Exercise Endurance Time
Participants were asked to exercise until symptom limitation
Time frame: After one dose
Population: Number of participants determined by previous studies. Analysis was intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treadmill Exercise With the Active Comparator | Exercise Endurance Time | 490 seconds | Standard Deviation 258 |
| Cycle Exercise With the Active Comparator | Exercise Endurance Time | 333 seconds | Standard Deviation 158 |
| Treadmill Exercise With the Placebo Comparator | Exercise Endurance Time | 472 seconds | Standard Deviation 258 |
| Cycle Exercise With the Placebo Comparator | Exercise Endurance Time | 362 seconds | Standard Deviation 104 |
Comparison: ANOVA was used to examine the interaction between mode of exercise and treatment effect.~Twenty patients were considered adequate to provide a power of 85% with an alpha of 0.05.p-value: <0.05ANOVA
Comparison: Comparing arformoterol with placebo with treadmill exercisep-value: 0.024t-test, 2 sided
Comparison: Arformoterol versus normal saline with cycle exercisep-value: 0.038t-test, 2 sided
Secondary
Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise
linear regression slope of breathlessness - time for arformoterol and for normal saline will be compared between treadmill and cycle exercise The higher the number the worse the shortness of breath
Time frame: After one dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treadmill Exercise With the Active Comparator | Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise | 1.27 breathlessness units/min | Standard Deviation 0.56 |
| Cycle Exercise With the Active Comparator | Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise | 1.79 breathlessness units/min | Standard Deviation 1.05 |
| Treadmill Exercise With the Placebo Comparator | Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise | 1.42 breathlessness units/min | Standard Deviation 0.97 |
| Cycle Exercise With the Placebo Comparator | Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise | 1.49 breathlessness units/min | Standard Deviation 0.59 |