Effects of Tiotropium on Breathing Capacity and Exercise Limitation in Early Stages of Chronic Obstructive Pulmonary Disease

NCT01072396 | Completed Phase 4 Results

• 1 other identifier: 205.440
• Study Type: interventional
• Target: 126
• Locations: 2 countries
• Sites: 15

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Inspiratory Capacity (IC) at Isotime

  Inspiratory capacity (IC) during CWR exercise testing measured at isotime (isotime was established during CWR exercise testing at baseline). Isotime is the minimum exercise time among all tests. Constant work rate exercise means the exercise is done under constant work rate.

  baseline, six weeks of treatment

Secondary Outcomes (2)

• Constant Work Rate (CWR) Endurance Time

  six weeks of treatment

• Change From Baseline in Modified Borg Scale Ratings for Dyspnea Intensity at Isotime

  baseline, six weeks of treatment

Study Arms (3)

18 mcg tiotropium

ACTIVE COMPARATOR

Patient to receive 1 tiotropium bromide inhalation powder capsule daily (in the morning) via HandiHaler

Drug: Tiotropium

Placebo

PLACEBO COMPARATOR

Patient to receive 1 placebo inhalation powder capsule daily (in the morning) identical to those containing tiotropium bromide inhalation powder via HandiHaler

Drug: Placebo

Control

NO INTERVENTION

Age and gender matched control subjects to conduct incremental and constant work rate exercise tests for comparison to subjects with early stage COPD

Interventions

Tiotropium DRUG

double blind randomized crossover

18 mcg tiotropium

Placebo DRUG

inhalation powder capsule identical to those containing tiotropium bromide inhalation powder

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (15)

205.440.1006 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

205.440.1015 Boehringer Ingelheim Investigational Site

Jasper, Alabama, United States

Location

205.440.1002 Boehringer Ingelheim Investigational Site

Torrance, California, United States

Location

205.440.1018 Boehringer Ingelheim Investigational Site

Hartford, Connecticut, United States

Location

205.440.1008 Boehringer Ingelheim Investigational Site

Springfield, Illinois, United States

Location

205.440.1017 Boehringer Ingelheim Investigational Site

Muncie, Indiana, United States

Location

205.440.1020 Boehringer Ingelheim Investigational Site

Livonia, Michigan, United States

Location

205.440.1011 Boehringer Ingelheim Investigational Site

Lebanon, New Hampshire, United States

Location

205.440.1019 Boehringer Ingelheim Investigational Site

Charlotte, North Carolina, United States

Location

205.440.1013 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

205.440.1007 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

205.440.2003 Boehringer Ingelheim Investigational Site

Kingston, Ontario, Canada

Location

205.440.2001 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

205.440.2004 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

205.440.2002 Boehringer Ingelheim Investigational Site

Ste-Foy, Quebec, Canada

Location

Related Publications (4)

• 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.

  PMID: 26775292 DERIVED

• 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.

  PMID: 25906326 DERIVED

• 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.

  PMID: 25289942 DERIVED

• 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.

  PMID: 24788342 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2010
• First Posted: February 22, 2010
• Study Start: February 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 24, 2013
• Results First Posted: May 15, 2013

Record last verified: 2013-04

Locations

CA (4); US (11)