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

Effects of Arformoterol on Exercise Endurance Time and Breathlessness in COPD: Cycle Ergometer vs. Treadmill

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Arformoterol tartrate; Other: Treadmill Exercise; Other: Cycle Exercise; Drug: Placebo: Normal Saline

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0001
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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	Other: Treadmill Exercise; Other: Cycle Exercise; Drug: Placebo: Normal Saline; Normal saline was nebulized.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	After one dose

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Sunovion
• Investigators: Principal Investigator: Doanld A Mahler, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

General Publications

• Zhang X, Waterman LA, Ward J, Baird JC, Mahler DA. Advantages of endurance treadmill walking compared with cycling to assess bronchodilator therapy. Chest. 2010 Jun;137(6):1354-61. doi: 10.1378/chest.09-2470. Epub 2009 Dec 29.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: September 16, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 29, 2013
• Last Update Submitted That Met QC Criteria: May 28, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: exercise;; treadmill;; cycle ergometer;; breathlessness;; leg discomfort
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: 21261