Investigating the Effects of Symbicort on the Ventilatory Kinematics in Patients With Obstructive Disease With Optoelectronic Plethysmography

This study has been terminated.
(The study was terminated as the medications for the study expired September of 2012.)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Matthew N. Bartels, Columbia University
ClinicalTrials.gov Identifier:
NCT01712854
First received: October 21, 2012
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to investigate how budesonide/formoterol fumarate dihydrate (Symbicort ©) affects dynamic hyperinflation in patients with obstructive disease using Optoelectronic Plethysmography (OEP). This study is unique as it will be the first randomized, doubleblind, crossover study with a placebo inhaler and budesonide/formoterol fumarate dihydrate as the intervention which will evaluate the effects on ventilatory mechanics through the use of OEP. The investigators plan to demonstrate that budesonide/formoterol fumarate dihydrate impacts dynamic hyperinflation which can be detected with OEP, and that budesonide/formoterol fumarate dihydrate may have an effect in the short term on exercise capacity during a constant load exercise test. The changes in ventilatory mechanics measured after budesonide/formoterol fumarate dihydrate by OEP will provide a unique evaluation of budesonide/formoterol fumarate dihydrate in a controlled setting also demonstrating the utility of OEP in evaluating of the effects of a medical treatment on hyperinflation in individuals with chronic obstructive lung disease (COPD).

  1. Primary Objective/Hypothesis: Our objective is to measure baseline, post treatment and post exercise spirometry and evaluate exercise dynamic hyperinflation before and after treatment using OEP. The investigators hypothesize that budesonide/formoterol fumarate dihydrate will decrease dynamic hyperinflation as measured by OEP.
  2. Primary Endpoint: Our primary endpoint is the change in dynamic hyperinflation, specifically end expiratory volumes, dynamic lung volumes and diaphragmatic paradoxical breathing as measured by OEP.
  3. Secondary Objective: Our secondary objective is to evaluate duration of steady state exercise and exercise capacity before and after treatment. Our secondary hypothesis is that decreases in dynamic hyperinflation during exercise will lead to improvements in dyspnea with exercise, and allow for increases in exercise capacity.
  4. Secondary endpoint: Exercise time, change in Borg scale at rest vs. Borg scale at steady state vs. Borg at end exercise.

Condition Intervention Phase
Chronic Obstructive Lung Disease
Drug: budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg inhaler
Drug: budesonide 80 mcg
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: Investigating the Effects of Symbicort on the Ventilatory Kinematics in Patients With Obstructive Disease With Optoelectronic Plethysmography

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • The change in dynamic hyperinflation measured by end expiratory volumes recorded by optoelectronic plethysmography (OEP). [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    Our objective is to measure baseline, post treatment and post exercise spirometry and evaluate exercise dynamic hyperinflation before and after treatment using OEP. We hypothesize that budesonide/formoterol fumarate dihydrate will decrease dynamic hyperinflation as measured by OEP.


Secondary Outcome Measures:
  • Exercise time in steady state exercise [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    Our secondary objective is to evaluate duration of steady state exercise and exercise capacity before and after treatment. Our secondary hypothesis is that decreases in dynamic hyperinflation during exercise will lead to improvements in dyspnea with exercise, and allow for increases in exercise capacity.


Enrollment: 9
Study Start Date: March 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg
Active medication.
Drug: budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg inhaler
INhaled long acting beta agonist and inhaled steroid versus inhaled steroid alone.
Other Name: budesonide/formoterol fumarate dihydrate versus budesonide only
Placebo Comparator: budesonide 80 mcg
placebo with no long acting beta agonist
Drug: budesonide 80 mcg

Detailed Description:

This study will be a prospective, randomized, double blind, crossover interventional design. The crossover allows for equality in number of subjects assigned to each treatment and for subjects to be their own controls. Baseline spirometry will be taken prior to exercise test. Subjects will be prepared for OEP. All exercise will take place on an electromagnetically braked cycle ergometer. Throughout the protocol heart rate, blood pressure, O2 saturation, ventilation, and metabolic data will be recorded. A modified exercise induced asthma protocol will be used. Unlike prior studies, ventilatory kinematics (with isolated diaphragmatic function) will be monitored throughout exercise using biomechanical motion analysis (OEP). This OEP analysis involves compartmentalization of the chest into three sections; 1) pulmonary rib cage, 2) diaphragmatic rib cage, and 3) abdomen to determine the contribution of each component to total lung volume. By measuring the percent contribution of compartment, we are able to better understand its impact on respiration. OEP will be able to quantify and assess the distortion effects of dynamic hyperinflation and obstruction.

Twenty moderate to severe COPD patients will be recruited. Subjects will refrain from their usual inhaled medications for 24 hours prior to the testing session. All subjects will be asked to verify that this is acceptable with their pulmonologist prior to participation. Subjects will also be asked to have their short acting bronchodilators and other regular medications available to be taken if symptoms should occur. During the initial screening, subjects will be familiarized with all procedures. Then baseline pulmonary function testing, and baseline resting OEP measurements will be performed. The subjects will then be randomized to receive either budesonide/formoterol fumarate dihydrate or a placebo. At that time, they will receive treatment with either placebo or budesonide/formoterol fumarate dihydrate and after 45 minutes, they will repeat spirometry and OEP and submaximal exercise testing with OEP. After one week, subjects will be tested again and switched to the opposite treatment (i.e. if on budesonide/formoterol fumarate dihydrate initially then switch to placebo and vice versa). The one week washout period between tests will include a resumption of the usual medications. The subjects will refrain from their inhaled medications for 24 hours before the second testing session, but use all of their other usual medications.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Moderate to severe COPD by GOLD criteria
  • Approval by pulmonologist
  • Informed consent
  • Age 40 to 75
  • Males and females
  • All races
  • Ex smoker or non smoker
  • Prior therapy allowed

Exclusion Criteria:

  • No active cardiac disease
  • Alpha1 Antitrypsin Deficiency
  • Active smoking
  • Reactive Airways Disease
  • Pulmonary Hypertension
  • Comorbid conditions preventing exercise (arthritic, neurologic, vascular, or other conditions)
  • BMI>30
  • Current enrollment in any other concurrent study at Columbia University Medical Center or sponsored by AstraZeneca at any other sites
  • Participation in any pharmacologic studies in the last 6 months prior to enrollment in this 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: NCT01712854

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
AstraZeneca
Investigators
Principal Investigator: Matthew Bartels, MD, MPH Columbia University
  More Information

No publications provided

Responsible Party: Matthew N. Bartels, John A. Downey Associate Professor of Clinical Rehabilitation Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01712854     History of Changes
Other Study ID Numbers: AAAI1932
Study First Received: October 21, 2012
Last Updated: October 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
COPD
Chronic Obstructive Lung Disease
Long acting beta agonist

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Budesonide
Formoterol
Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014