Effects of Tiotropium on Breathing Capacity and Exercise Limitation in Early Stages of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Optimal clinical management in early stages of COPD is not established. Tiotropium has been shown to improve exercise tolerance during (CWR) cycle ergometry with GOLD stage II to IV COPD, improvements in constant speed treadmill time in a study of patients who also received pulmonary rehabilitation in a population of patients with predominantly severe and very severe disease (GOLD stages III and IV) and improvements in exertional dyspnea, and Shuttle Walk Test distance in GOLD stage III and IV COPD. However, data are lacking on the benefits of tiotropium on exercise tolerance in a patients with early stages of COPD who are symptomatic. Patients with milder ventilatory limitations (GOLD stages I/II COPD patients) may benefit from maintenance therapy and there is limited data on exercise limitation in patients with early stage COPD who are symptomatic. This study is designed to evaluate the mechanisms of breathlessness and assess physical activity limitation in early stage COPD patients compared to age and gender matched controls and will secondly investigate the effectiveness of treatment with tiotropium in improving dyspnea during exercise and exercise duration as a result of the bronchodilation effects of tiotropium leading to a reduction of dynamic hyperinflation in Early Stage COPD patients.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 6-week, Crossover Study to Examine the Effects of Tiotropium (Spiriva® HandiHaler®, 18 µg Once Daily) on Dynamic Hyperinflation and Physical Exercise Capacity in Patients With Early Stage Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: For COPD subjects: Male or female, age of 40 years or older, smoking history >10 pack-years, symptomatic defined as baseline dyspnea index focal score of 9 or more and / or daily cough with production of sputum for three months per year during at least two consecutive years, diagnosis of early stage COPD according to: post-bronchodilator FEV1/FVC ratio <70%., FEV1 >/=50% post-bronchodilator predicted normal, and a decreased Inspiratory Capacity during exercise. For Age / Gender Matched Controls: Male or female, age of 40 years or older, nonsmoker, with no significant diseases. Exclusion criteria: Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study. Patients with a history of asthma, Patients requiring the use of supplemental oxygen therapy, Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris, claudication or other conditions, or Patients with contraindications to exercise. Note: Additional exclusion criteria for Age / Gender Matched Controls: Patients with a significant disease including COPD.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 18 mcg tiotropium<br>Patient to receive 1 tiotropium bromide inhalation powder capsule daily (in the morning) via HandiHaler | Drug: Tiotropium<br>* double blind randomized crossover<br>|
| Placebo Comparator: Placebo<br>Patient to receive 1 placebo inhalation powder capsule daily (in the morning) identical to those containing tiotropium bromide inhalation powder via HandiHaler | Drug: Placebo<br>* inhalation powder capsule identical to those containing tiotropium bromide inhalation powder<br>|
| No Intervention: Control<br>Age and gender matched control subjects to conduct incremental and constant work rate exercise tests for comparison to subjects with early stage COPD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Inspiratory Capacity (IC) at Isotime | Inspiratory capacity (IC) during CWR exercise testing measured at isotime (isotime was established during CWR exercise testing at baseline). Isotime is the minimum exercise time among all tests. Constant work rate exercise means the exercise is done under constant work rate. | baseline, six weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Constant Work Rate (CWR) Endurance Time | CWR exercise duration calculated as the length of time of the exercise period | six weeks of treatment | 
| Change From Baseline in Modified Borg Scale Ratings for Dyspnea Intensity at Isotime | Modified Borg Scale is a participant rating of the intensity of dyspnea measured on a scale ranging from 0 (Nothing at all) to 10 (Maximal, most severe ever experienced). | baseline, six weeks of treatment |