Mechanisms of Dyspnea Relief During Exercise in COPD Patients Following Treatment With Tiotropium (Spiriva)

Randomised, Double-Blind, Placebo-Controlled, Cross-Over Study to Examine the Effects of Tiotropium on Lung Hyperinflation, Respiratory Mechanics and Dyspnea During Exercise in Patients With COPD

To explore the mechanisms of dyspnea relief during exercise in patients with COPD following treatment with tiotropium bromide (Spiriva)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: tiotropium bromide

Detailed Description

This was a single-centre, randomised, double-blind, placebo-controlled, cross-over study. The duration of subject participation was 9 weeks. There was an initial screening period of up to 2 weeks. The first screening visit consisted of medical history, clinical assessment, chronic dyspnea evaluation, complete pulmonary function testing, and a symptom-limited maximal incremental cycle exercise test. A second visit during the screening period was intended as a training of the subject to the procedures to be performed in the study, with specific focus on familiarisation with the constant work rate exercise test. The screening period was followed by 2 x 7 day treatment periods (1 x tiotropium and 1 x placebo), separated by a 4 week washout period. On the last day of each treatment period, the subject visited the clinic to complete a series of trial related procedures, including lung function measurements and a constant work rate exercise test at 75% Wcap to symptom limitation. Testing consisted of pulmonary function testing, dyspnea evaluation, and symptom-limited constant-load cycle exercise tests with measurements of cardiopulmonary parameters, symptom intensity and pulmonary mechanics. \

Study Hypothesis:

Dynamic hyperinflation restricts volume expansion during exercise and is suspected as a primary mechanism of dyspnea. The dissociation between drive or muscular effort to breathe and the mechanical response to increased volume (as reflected by an increased Pes/PImax: VT/predicted VC ratio) correlates well with the intensity of inspiratory difficulty during exercise in COPD. It was hypothesised that reduced Borg ratings at a standardized exercise level after tiotropium would correlate strongly with reduced restricted volume expansion during exercise (i.e., increased VT/IC and EILV/TLC ratios, and decreased IC and IRV). In other words, dyspnea and its predominant qualitative dimensions (i.e., inspiratory difficulty) result from patients being forced by DH to breathe at a high lung volume, at or above predicted TLC.

Comparison(s):

tiotropium bromide (Spiriva) vs. placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V6
      • Kingston General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria: Patients with chronic obstructive pulmonary disease (COPD) with FEV1 < 70% predicted and FRC > 120% predicted, a cigarette smoking history > 20 pack-years, and moderate to severe chronic dyspnea

Exclusion criteria: patients with a history of asthma, allergic rhinitis or atopy; patients who participated in a rehabilitation program for COPD within 6 weeks prior to screening

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Borg dyspnea rating at a standardized exercise time (DyspneaSTD) during a constant work rate exercise challenge to symptom limitation at 75% maximal work capacity	up to 7 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Endurance time	up to 7 weeks
Borg leg discomfort	up to 7 weeks
Qualitative aspects of dyspnea	up to 7 weeks
Locus of sensory limitation	7 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim Study Coordinator, B.I. Canada Ltd.

Publications and helpful links

General Publications

• Travers J, Laveneziana P, Webb KA, Kesten S, O'Donnell DE. Effect of tiotropium bromide on the cardiovascular response to exercise in COPD. Respir Med. 2007 Sep;101(9):2017-24. doi: 10.1016/j.rmed.2007.03.008. Epub 2007 May 1.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): March 1, 2003
• Study Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: January 9, 2006
• First Submitted That Met QC Criteria: January 9, 2006
• First Posted (Estimate): January 10, 2006

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: 205.231