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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00274027
First received: January 9, 2006
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: tiotropium bromide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Endurance time [ Time Frame: up to 7 weeks ] [ Designated as safety issue: No ]
  • Borg leg discomfort [ Time Frame: up to 7 weeks ] [ Designated as safety issue: No ]
  • Qualitative aspects of dyspnea [ Time Frame: up to 7 weeks ] [ Designated as safety issue: No ]
  • Locus of sensory limitation [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: January 2001
Study Completion Date: March 2003
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
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

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274027

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

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00274027     History of Changes
Other Study ID Numbers: 205.231
Study First Received: January 9, 2006
Last Updated: October 31, 2013
Health Authority: Canada: Health Canada (TPD)

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Lung Diseases, Obstructive
Bromides
Tiotropium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 24, 2014