Dynamic Hyperinflation and Tiotropium

Study Overview
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Brief Summary
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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
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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

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

Conditions
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COPD

Intervention / Treatment
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* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tiotropium 18 µg capsule, bronchodilator<br>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<br>* 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<br>|
| Placebo Comparator: 2<br>placebo 18ug tiotropium for 1 month | Drug: Placebo<br>* 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<br>|

What is the study measuring?
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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 |