Dynamic Hyperinflation and Tiotropium

This study has been completed.
Sponsor:
Collaborators:
Boehringer Ingelheim
Pfizer
Information provided by (Responsible Party):
Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier:
NCT00569270
First received: December 6, 2007
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
COPD
Drug: tiotropium
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Simplified Detection of Dynamic Hyperinflation Using Metronome Paced Hyperventilation and the Effect of Tiotropium in Patients With COPD

Resource links provided by NLM:


Further study details as provided by Gelb, Arthur F., M.D.:

Primary Outcome Measures:
  • Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)- [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium [ Time Frame: baseline to 30 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Enrollment: 30
Study Start Date: October 2006
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: tiotropium
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
Other Name: Spiriva
Drug: tiotropium
daily tiotropium 18ug versus daily placebo for 30 days
Other Name: Spiriva
Placebo Comparator: 2
placebo 18ug tiotropium for 1 month
Drug: tiotropium
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
Other Name: Spiriva
Drug: placebo
18ug tiotropium placebo capsule daily for 1 month
Drug: tiotropium
daily tiotropium 18ug versus daily placebo for 30 days
Other Name: Spiriva

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

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569270

Locations
United States, California
Arthur F Gelb MD
Lakewood, California, United States, 90712
Canada, Ontario
Noe Zamel MD
Toronto, Ontario, Canada
Sponsors and Collaborators
Gelb, Arthur F., M.D.
Boehringer Ingelheim
Pfizer
Investigators
Principal Investigator: Arthur F Gelb, MD Arthur F Gelb Medical Corporation
Principal Investigator: Noe Zamel, MD Mt. Sinai Hosp. Toronto, Univ Toronto Medical Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier: NCT00569270     History of Changes
Other Study ID Numbers: 20061693, IIS Boehringer-Ingelheim, IIS Pfizer
Study First Received: December 6, 2007
Results First Received: August 20, 2011
Last Updated: October 4, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014