Clinical trial NCT01072396: Effects of Tiotropium on Breathing Capacity and Exercise Limitation in Early Stages of Chronic Obstructive Pulmonary Disease
Official title: A Randomized, Double-blind, Placebo-controlled, 6-week, Crossover Study to Examine the Effects of Tiotropium (Spiriva® HandiHaler®, 18 µg Once Daily) on Dynamic Hyperinflation and Physical Exercise Capacity in Patients With Early Stage Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2010-02-22
Enrollment: 126
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Optimal clinical management in early stages of COPD is not established. Tiotropium has been shown to improve exercise tolerance during (CWR) cycle ergometry with GOLD stage II to IV COPD, improvements in constant speed treadmill time in a study of patients who also received pulmonary rehabilitation in a population of patients with predominantly severe and very severe disease (GOLD stages III and IV) and improvements in exertional dyspnea, and Shuttle Walk Test distance in GOLD stage III and IV COPD. However, data are lacking on the benefits of tiotropium on exercise tolerance in a patients with early stages of COPD who are symptomatic. Patients with milder ventilatory limitations (GOLD stages I/II COPD patients) may benefit from maintenance therapy and there is limited data on exercise limitation in patients with early stage COPD who are symptomatic. This study is designed to evaluate the mechanisms of breathlessness and assess physical activity limitation in early stage COPD patients compared to age and gender matched controls and will secondly investigate the effectiveness of treatment with tiotropium in improving dyspnea during exercise and exercise duration as a result of the bronchodilation effects of tiotropium leading to a reduction of dynamic hyperinflation in Early Stage COPD patients.


Eligibility criteria: Inclusion criteria:

For COPD subjects: Male or female, age of 40 years or older, smoking history \>10 pack-years, symptomatic defined as baseline dyspnea index focal score of 9 or more and / or daily cough with production of sputum for three months per year during at least two consecutive years, diagnosis of early stage COPD according to: post-bronchodilator FEV1/FVC ratio \<70%., FEV1 \>/=50% post-bronchodilator predicted normal, and a decreased Inspiratory Capacity during exercise. For Age / Gender Matched Controls: Male or female, age of 40 years or older, nonsmoker, with no significant diseases.

Exclusion criteria:

Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study.

Patients with a history of asthma, Patients requiring the use of supplemental oxygen therapy, Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris, claudication or other conditions, or Patients with contraindications to exercise.

Note: Additional exclusion criteria for Age / Gender Matched Controls: Patients with a significant disease including COPD.

Primary outcomes:
measure: Change From Baseline in Inspiratory Capacity (IC) at Isotime
timeFrame: baseline, six weeks of treatment
Secondary outcomes:
measure: Constant Work Rate (CWR) Endurance Time
timeFrame: six weeks of treatment
measure: Change From Baseline in Modified Borg Scale Ratings for Dyspnea Intensity at Isotime
timeFrame: baseline, six weeks of treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 205.440.1006 Boehringer Ingelheim Investigational Site
state: Alabama
city: Jasper
country: United States
facility: 205.440.1015 Boehringer Ingelheim Investigational Site
state: Alabama
city: Torrance
country: United States
facility: 205.440.1002 Boehringer Ingelheim Investigational Site
state: California
city: Hartford
country: United States
facility: 205.440.1018 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Springfield
country: United States
facility: 205.440.1008 Boehringer Ingelheim Investigational Site
state: Illinois
city: Muncie
country: United States
facility: 205.440.1017 Boehringer Ingelheim Investigational Site
state: Indiana
city: Livonia
country: United States
facility: 205.440.1020 Boehringer Ingelheim Investigational Site
state: Michigan
city: Lebanon
country: United States
facility: 205.440.1011 Boehringer Ingelheim Investigational Site
state: New Hampshire
city: Charlotte
country: United States
facility: 205.440.1019 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: 205.440.1013 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: 205.440.1007 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Kingston
country: Canada
facility: 205.440.2003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 205.440.2001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 205.440.2004 Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: 205.440.2002 Boehringer Ingelheim Investigational Site
state: Quebec
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Porszasz J, Blonshine S, Cao R, Paden HA, Casaburi R, Rossiter HB. Biological quality control for cardiopulmonary exercise testing in multicenter clinical trials. BMC Pulm Med. 2016 Jan 16;16:13. doi: 10.1186/s12890-016-0174-8.
citation: Gagnon P, Casaburi R, Saey D, Porszasz J, Provencher S, Milot J, Bourbeau J, O'Donnell DE, Maltais F. Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease. PLoS One. 2015 Apr 23;10(4):e0123626. doi: 10.1371/journal.pone.0123626. eCollection 2015.
citation: Casaburi R, Maltais F, Porszasz J, Albers F, Deng Q, Iqbal A, Paden HA, O'Donnell DE; 205.440 Investigators. Effects of tiotropium on hyperinflation and treadmill exercise tolerance in mild to moderate chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014 Nov;11(9):1351-61. doi: 10.1513/AnnalsATS.201404-174OC.
citation: O'Donnell DE, Maltais F, Porszasz J, Webb KA, Albers FC, Deng Q, Iqbal A, Paden HA, Casaburi R; 205.440 investigators. The continuum of physiological impairment during treadmill walking in patients with mild-to-moderate COPD: patient characterization phase of a randomized clinical trial. PLoS One. 2014 May 1;9(5):e96574. doi: 10.1371/journal.pone.0096574. eCollection 2014.