Dynamic Hyperinflation and Tiotropium

Simplified Detection of Dynamic Hyperinflation Using Metronome Paced Hyperventilation and the Effect of Tiotropium in Patients With COPD

We will detect dynamic hyperinflation (DH) in 40 COPD (chronic obstructive pulmonary disease) patients with moderately severe disease using metronome paced hyperventilation (MPH) with inspiratory capacity as the primary end point. Hypothesis: Is tiotropium capable of lung volume protecting inspiratory capacity from MPH induced DH vs placebo in a randomized crossover double blinded study.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo

Detailed Description

Study completed with 29 patients studied. Data is being analyzed to evaluate trough and peak effect of 18 µg tiotropium vs placebo on FEV 1 (L)(forced expiratory capacity in one second), inspiratory capacity and functional residual volume. In addition, we will study the effect of 18 µg tiotropium vs placebo on metronome paced hyperventilation induced dynamic hyperinflation. We will also evaluate the effect of tiotropium induced increase in IC (inspiratory capacity) vs extent of emphysema as evaluated on high resolution thin section CT lung

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Noe Zamel MD
• United States
  • California
    • Lakewood, California, United States, 90712
      • Arthur F Gelb MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderately severe COPD patients age 40-85 yr with post 180ug albuterol FEV 1 between 60 and 79% predicted and FEV 1/FVC < 70%.
• Smoking history > 10 pack yr.
• Clinically stable X 6 weeks.
• No oxygen usage.

Exclusion Criteria:

• History of asthma
• Clinically unstable
• Any other significant medical problem precluding full cooperation for study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tiotropium 18 µg capsule, bronchodilator; tiotropium 18 µg capsule for 1 month versus placebo. To study bronchodilation and effect following metronome paced hyperventilation and induced dynamic hyperinflation of active tiotropium versus placebo	Drug: Placebo; Procedure/Surgery - tiotropium 18ug capsule daily for 1 month vs placebo to study the effect of trough and peak effect on bronchodilation and effect of metronome paced hyperventilation induced dynamic hyperinflation
Placebo Comparator: 2; placebo 18ug tiotropium for 1 month	Drug: Placebo; Procedure/Surgery - tiotropium 18ug capsule daily for 1 month vs placebo to study the effect of trough and peak effect on bronchodilation and effect of metronome paced hyperventilation induced dynamic hyperinflation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)-	Lung function studies (mean +/- SD): peak FEV1 (+2h) after 30 days of placebo or tiotropium in 29 moderate COPD patients. FEV1 = Forced expiratory volume in one second	30 days
Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity)	Lung function studies (mean +/- SD): peak FRC after 30 days (+2h) of placebo or tiotropium in 29 moderate COPD patients.	30 days
Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo	Lung function studies (mean +/- SD) of peak forced vital capaciy (L) after 30 days (+2h) of tiotropium versus placebo in 29 moderate COPD patients. Forced vital capacity - liters	30 days
Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo	Lung function studies (mean +/- SD) - Peak inspiratory capacity after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Inspiratory capacity- liters	30 days
Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo	Lung function studies (mean +/- SD) peak Peak FRC/TLC after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity/total lung capacity - percentage	30 days
Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo	Net change in lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients. Total lung capacity - liters	30 days
Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo	Lung function studies Trough FEV1(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Forced expiratory volume in 1s (liters)	30 days
Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo	Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters)	30 days
Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo	Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients	30 days
Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo	Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters	30 days
Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo	Lung function studies Trough FRC/TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough Functional residual capacity/total lung capacity - percentage	30 days
Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo	Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients	30 days
IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline	IC measurement before and after metronome paced hyperventilation-induced dynamic hyperinflation at baseline and in tiotropium and placebo groups. Measure ratio of functional residual capacity divided by total lung capacity at baseline and after 30 days of tiotropium versus placebo	baseline and 30 days (+2h) post dose
TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo	Total lung capacity before and after metronome paced hyperventilation induced dynamic hyperinflation in tiotropium cohort versus placebo. Difference between TLC measured at one hour before intervention & 2 hrs. after after 30 days of treatment with either placebo or tiotropium	one hour before intervention & 2 hrs. after after 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium	Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to FEV 1; correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema; measures include increase in FEV1 from baseline to peak tiotropium	baseline to 30 days
IC (Inspiratory Capacity, L) Post Mph (Metronome Paced Hyperventilation) Induced dh (Dynamic Hyperinflation) After Tiotropium and Extent of Lung CT Scored Emphysema	Correlation between change in inspiratory capacity (L) post metronome paced hyperventilation induced dynamic hyperinflation and extent of lung ct scored emphysema	baseline to 30 days
Extent of Lung CT Scored Emphysema and and Lung Function of FRC/TLC (Functional Residual Capacity(L)/Total Lung Capacity (L) After Tiotropium	Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema	baseline to trough tiotropium

Collaborators and Investigators

• Sponsor: Gelb, Arthur F., M.D.
• Collaborators: Pfizer; Boehringer Ingelheim
• Investigators: Principal Investigator: Noe Zamel, MD, Mt. Sinai Hosp. Toronto, Univ Toronto Medical Center

Publications and helpful links

General Publications

• Gelb AF, Taylor CF, McClean PA, Shinar CM, Rodrigues MT, Gutierrez CA, Chapman KR, Zamel N. Tiotropium and simplified detection of dynamic hyperinflation. Chest. 2007 Mar;131(3):690-695. doi: 10.1378/chest.06-1662.
• Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60. doi: 10.1378/chest.126.6.1855.
• Gelb AF, Fraser C, Zamel N. Lack of protective effect of tiotropium vs induced dynamic hyperinflation in moderate COPD. Respir Med. 2011 May;105(5):755-60. doi: 10.1016/j.rmed.2010.11.020. Epub 2010 Dec 14.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: December 6, 2007
• First Submitted That Met QC Criteria: December 6, 2007
• First Posted (Estimate): December 7, 2007

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 10, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 20061693; IIS Boehringer-Ingelheim (Other Grant/Funding Number: Boehringer-Ingelheim and Pfizer); IIS Pfizer (Other Grant/Funding Number: Pfizer)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Please see published data