Dynamic Hyperinflation and Tiotropium

Overview

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.

Full Title of Study: “Simplified Detection of Dynamic Hyperinflation Using Metronome Paced Hyperventilation and the Effect of Tiotropium in Patients With COPD”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 2009

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

Interventions

  • 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

Arms, Groups and Cohorts

  • 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
  • Placebo Comparator: 2
    • placebo 18ug tiotropium for 1 month

Clinical Trial Outcome Measures

Primary Measures

  • Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)-
    • Time Frame: 30 days
    • 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
  • Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity)
    • Time Frame: 30 days
    • Lung function studies (mean +/- SD): peak FRC after 30 days (+2h) of placebo or tiotropium in 29 moderate COPD patients.
  • Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo
    • Time Frame: 30 days
    • 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
  • Bronchodilator Response: Peak IC (L) – (Inspiratory Capacity) – Tiotropium Versus Placebo
    • Time Frame: 30 days
    • Lung function studies (mean +/- SD) – Peak inspiratory capacity after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Inspiratory capacity- liters
  • Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) – Tiotropium or Placebo
    • Time Frame: 30 days
    • 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
  • Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo
    • Time Frame: 30 days
    • 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
  • Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo
    • Time Frame: 30 days
    • 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)
  • Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo
    • Time Frame: 30 days
    • Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters)
  • Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo
    • Time Frame: 30 days
    • Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
  • Bronchodilator Response: Trough IC (L) Inspiratory Capacity – Tiotropium Versus Placebo
    • Time Frame: 30 days
    • Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters
  • Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo
    • Time Frame: 30 days
    • 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
  • Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo
    • Time Frame: 30 days
    • Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
  • IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline
    • Time Frame: baseline and 30 days (+2h) post dose
    • 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
  • TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo
    • Time Frame: one hour before intervention & 2 hrs. after after 30 days
    • 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

Secondary Measures

  • Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium
    • Time Frame: baseline to 30 days
    • 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
  • IC (Inspiratory Capacity, L) Post Mph (Metronome Paced Hyperventilation) Induced dh (Dynamic Hyperinflation) After Tiotropium and Extent of Lung CT Scored Emphysema
    • Time Frame: baseline to 30 days
    • Correlation between change in inspiratory capacity (L) post metronome paced hyperventilation induced dynamic hyperinflation and extent of lung ct scored emphysema
  • Extent of Lung CT Scored Emphysema and and Lung Function of FRC/TLC (Functional Residual Capacity(L)/Total Lung Capacity (L) After Tiotropium
    • Time Frame: baseline to trough 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Gelb, Arthur F., M.D.
  • Collaborator
    • Boehringer Ingelheim
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Arthur F Gelb, MD, Principal Investigator, Arthur F Gelb Medical Corporation
    • Noe Zamel, MD, Principal Investigator, Mt. Sinai Hosp. Toronto, Univ Toronto Medical Center

References

Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60.

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.

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