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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00274027
Recruitment Status : Completed
First Posted : January 10, 2006
Last Update Posted : November 1, 2013
Information provided by:
Boehringer Ingelheim

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

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: tiotropium bromide Phase 3

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.


tiotropium bromide (Spiriva) vs. placebo

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2001
Actual Primary Completion Date : March 2003
Actual Study Completion Date : March 2003

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Borg dyspnea rating at a standardized exercise time (DyspneaSTD) during a constant work rate exercise challenge to symptom limitation at 75% maximal work capacity [ Time Frame: up to 7 weeks ]

Secondary Outcome Measures :
  1. Endurance time [ Time Frame: up to 7 weeks ]
  2. Borg leg discomfort [ Time Frame: up to 7 weeks ]
  3. Qualitative aspects of dyspnea [ Time Frame: up to 7 weeks ]
  4. Locus of sensory limitation [ Time Frame: 7 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00274027

Canada, Ontario
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V6
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Canada Ltd.

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00274027     History of Changes
Other Study ID Numbers: 205.231
First Posted: January 10, 2006    Key Record Dates
Last Update Posted: November 1, 2013
Last Verified: October 2013

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action