ARFEET: Effect of Bronchodilation on Cycle vs Treadmill Exercise Endurance Time in COPD

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00754546
• Collaborator: Sunovion (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Arformoterol tartrate; Drug: Placebo: Normal Saline; Other: Treadmill Exercise; Other: Cycle Exercise	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Arformoterol on Exercise Endurance Time and Breathlessness in COPD: Cycle Ergometer vs. Treadmill
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arformoterol tartrate Bronchodilator therapy with arformoterol solution 15 mcg	Drug: Arformoterol tartrate; 15 mcg in two ml solution administered via nebulizer; Other Names: Brovana ; Other: Treadmill Exercise; Other: Cycle Exercise
Placebo Comparator: Normal saline Placebo using normal saline	Drug: Placebo: Normal Saline; Normal saline was nebulized.; Other: Treadmill Exercise; Other: Cycle Exercise

Outcome Measures

Primary Outcome Measures

1. Exercise Endurance Time [After one dose]

   Participants were asked to exercise until symptom limitation

Secondary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0001

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center
• Sunovion

Investigators

• Principal Investigator: Doanld A Mahler, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT00754546
• Other Study ID Numbers: 21261
• First Posted: Sep 18, 2008
• Last Update Posted: May 29, 2013
• Last Verified: May 1, 2013

• Keywords provided by Dartmouth-Hitchcock Medical Center: exercise;; treadmill;; cycle ergometer;; breathlessness;; leg discomfort
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Formoterol Fumarate

Study Results

Participant Flow

Recruitment Details	Participants recruited from a specialty clinic in Lebanon, NH, between August 1, 2008 to May 1, 2009.
Pre-assignment Detail	27 particpants recruited; 27 particpants screened; 5 excluded because they did not meet inclusion criteria; 2 patients withdrew consent after visit 1.

Arm/Group Title	All Participants
Arm/Group Description	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
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	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
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 60%
>=65 years	8 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (7)
Sex: Female, Male (Count of Participants)
Female	9 45%
Male	11 55%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Exercise Endurance Time
Description	Participants were asked to exercise until symptom limitation
Time Frame	After one dose

Outcome Measure Data

Analysis Population Description

Number of participants determined by previous studies. Analysis was intention to treat

Arm/Group Title	Treadmill Exercise With the Active Comparator	Cycle Exercise With the Active Comparator	Treadmill Exercise With the Placebo Comparator	Cycle Exercise With the Placebo Comparator
Arm/Group Description
Measure Participants	20	20	20	20
Mean (Standard Deviation) [seconds]	490 (258)	333 (158)	472 (258)	362 (104)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treadmill Exercise With the Active Comparator, Cycle Exercise With the Active Comparator, Treadmill Exercise With the Placebo Comparator, Cycle Exercise With the Placebo Comparator
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treadmill Exercise With the Active Comparator, Cycle Exercise With the Active Comparator, Treadmill Exercise With the Placebo Comparator, Cycle Exercise With the Placebo Comparator
	Comments	Comparing arformoterol with placebo with treadmill exercise
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treadmill Exercise With the Active Comparator, Cycle Exercise With the Active Comparator, Treadmill Exercise With the Placebo Comparator, Cycle Exercise With the Placebo Comparator
	Comments	Arformoterol versus normal saline with cycle exercise
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Linear Regression Between Breathlessness Ratings (on 0 - 10 Borg Scale) and Time Throughout Exercise
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treadmill Exercise With the Active Comparator	Cycle Exercise With the Active Comparator	Treadmill Exercise With the Placebo Comparator	Cycle Exercise With the Placebo Comparator
Arm/Group Description
Measure Participants	20	20	20	20
Least Squares Mean (Standard Deviation) [breathlessness units/min]	1.27 (0.56)	1.79 (1.05)	1.42 (0.97)	1.49 (0.59)

Adverse Events

Arm/Group Title	Treadmill Exercise With the Active Comparator		Cycle Exercise With the Active Comparator		Treadmill Exercise With the Placebo Comparator		Cycle Exercise With the Placebo Comparator
Arm/Group Description
All Cause Mortality
	Treadmill Exercise With the Active Comparator		Cycle Exercise With the Active Comparator		Treadmill Exercise With the Placebo Comparator		Cycle Exercise With the Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treadmill Exercise With the Active Comparator		Cycle Exercise With the Active Comparator		Treadmill Exercise With the Placebo Comparator		Cycle Exercise With the Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Treadmill Exercise With the Active Comparator		Cycle Exercise With the Active Comparator		Treadmill Exercise With the Placebo Comparator		Cycle Exercise With the Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)

Limitations/Caveats

Study completed with no reported adverse effects. One limitation of the study is frequent exercise tests involving 7 visits for each participant

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.