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

Phase 3

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive

• Registration Number: NCT00274027
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

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 Timeline

• Study Start: 2001-01
• Primary Completion: 2003-03
• Study Completion: 2003-03
• Study First Submitted: 2006-01-09
• Study First Submitted QC: 2006-01-09
• Study First Posted: 2006-01-10
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-31
• Last Update Posted: 2013-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Borg leg discomfort	up to 7 weeks
Qualitative aspects of dyspnea	up to 7 weeks
Endurance time	up to 7 weeks
Locus of sensory limitation	7 weeks

Trial Locations

Locations (1)

Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada