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Dynamic Hyperinflation and Tiotropium

Phase 4
Completed
Conditions
COPD
Interventions
Drug: Placebo
Registration Number
NCT00569270
Lead Sponsor
Gelb, Arthur F., M.D.
Brief Summary

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.

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Tiotropium 18 µg capsule, bronchodilatorPlacebotiotropium 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
2Placeboplacebo 18ug tiotropium for 1 month
Primary Outcome Measures
NameTimeMethod
Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)-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)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 Placebo30 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 FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo30 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 Placebo30 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 Placebo30 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 IC (L) Inspiratory Capacity - Tiotropium Versus Placebo30 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 TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo30 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 Baselinebaseline 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 Placeboone 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

Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo30 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: Trough FRC (L)- Tiotropium Versus Placebo30 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 Placebo30 days

Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo30 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

Secondary Outcome Measures
NameTimeMethod
Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropiumbaseline 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 Emphysemabaseline 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 Tiotropiumbaseline 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

Trial Locations

Locations (2)

Arthur F Gelb MD

🇺🇸

Lakewood, California, United States

Noe Zamel MD

🇨🇦

Toronto, Ontario, Canada

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