Effects of Tiotropium on Walking Capacity in Patients With COPD
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      This study was designed to test the following hypothesis:

      A) The acute and long-term (3 weeks) bronchodilator-induced changes in exercise tolerance and
      in the physiological response during the endurance shuttle walk will be greater with
      tiotropium compared to placebo in COPD patients.

      B) Three weeks of bronchodilation will be associated with increase activity of daily living
      as evaluated using the London Chest Activity Daily Living scale.
    

Detailed description: 
      Objectives:

      The purpose of this study is to compare the acute bronchodilator-induced changes in exercise
      tolerance during the endurance shuttle walk between tiotropium and placebo in COPD patients.
      Also, it will evaluate the physiological response (VE, VO2, VCO2, and heart rate) during the
      endurance shuttle walk in patients with COPD patients. Finally, it will compare the long-term
      (3 weeks) bronchodilator-induced changes in exercise tolerance during the endurance shuttle
      walk between tiotropium and placebo in COPD patients and evaluate the impact of long-term (3
      weeks) bronchodilation on activity of daily living evaluated using the London Chest Activity
      Daily Living scale.

      Methods:

      This will be a double-blind, randomized and parallel-group study. Due to the long action
      duration of tiotropium (up to 4 weeks), a cross-over design, as we used in our ipratropium
      versus placebo study, is not appropriate in the present study. The study will require five
      visits at the Centre de recherche de l'Hopital Laval. The first visit will include review of
      the consent form, pulmonary function testing, and a maximal incremental shuttle walk. The
      following two visits (Visit 2 and 3) will be used to familiarize the participants to the
      shuttle endurance walking test. Salbutamol and ipratropium bromide will be stopped 6 hours
      prior to these visits while the remaining medication allowed during the study period (see
      below) will be continued as prescribed. The goal of the familiarization will be to reduce the
      learning effect that typically occurs when an individual completes the same endurance test
      several times 3. On visit 4, patients will be randomized to receive one of the two
      treatments: placebo or tiotropium 18 ug (Spiriva) using the handihaler device. Pulmonary
      function testing will then be performed and the London Chest Activity Daily Living scale will
      be administered. Two hours following the inhalation of the first study dose, pulmonary
      function testing will be repeated and the patients will perform an endurance shuttle walk.
      They will be provided enough medication for the study duration and discharged. The same
      procedure as Visit 4 will be completed three weeks later, on visit 5.

      Data analysis:

      The main outcome will be endurance time at day 21. This variable will be compared between the
      two treatment arms using an unpaired t-test. The endurance time at day 0 will also be
      compared between the two treatment arms using the same procedure. The time course of the
      cardiorespiratory parameters and dyspnea over time will be compared between the two exercise
      modalities. Comparisons will be done using a repeated measure design (ANOVA). Significance
      level will be set at a p value of 0.05. The two familiarization endurance shuttle walk tests
      performed at day -10 and day -5 will be used to evaluate the test-retest variability of this
      procedure.
    

Intervention name(s): Tiotropium; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Tiotropium diskus inhalation powder, 18ug, once daily; Placebo diskus inhalation powder, once daily
Other intervention name(s): Spiriva
Intervention MeSH terms: Tiotropium Bromide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Chronic Obstructive Pulmonary Disease (COPD); Exercise; Endurance shuttle walking test; Bronchodilation; Tiotropium