Effects of Symbicort on the Ventilatory Kinematics

• Sponsor: Columbia University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01712854
• Collaborator: AstraZeneca (Industry)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Chronic Obstructive Lung Disease	Drug: Budesonide; Drug: Symbicort	Phase 4

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 (Symbicort) or a placebo of budesonide only (Entocort EC). 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Symbicort A combination of budesonide + long acting beta agonist (Symbicort): Budesonide 80 mcg and formoterol fumarate dihydrate inhaler 4.5 mcg	Drug: Symbicort; A combination of budesonide and long acting beta agonist: Budesonide 80 mcg and formoterol fumarate dihydrate inhaler 4.5 mcg
Placebo Comparator: Budesonide only Budesonide 80 mcg (Entocort EC) only	Drug: Budesonide; budesonide 80 mcg

Outcome Measures

Primary Outcome Measures

1. The Change in Dynamic Hyperinflation Measured by End Expiratory Volumes Recorded by Optoelectronic Plethysmography (OEP). [2 hours]

   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

1. Exercise Time in Steady State Exercise [2 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Moderate to severe COPD by Global Initiative for Chronic Obstructive Lung Disease (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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT01712854
• Other Study ID Numbers: AAAI1932
• First Posted: Oct 24, 2012
• Last Update Posted: Sep 2, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Columbia University: COPD; Chronic Obstructive Lung Disease; Long acting beta agonist
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Budesonide; Budesonide, Formoterol Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	The principal investigator has left the institution. Attempts to contact the PI have been unsuccessful. Columbia will never have access to the data. Thus, data will not be analyzed. The only information available is the number of participants who started and completed the study, which was last reported to and approved by the IRB in February 2013.

Arm/Group Title	Active Medication or Placebo
Arm/Group Description	Data per arm is not available. Columbia will never have access to this data.
Period Title: Overall Study
STARTED	9
COMPLETED	8
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Active Medication or Placebo
Arm/Group Description	Data per arm is not available. Columbia will never have access to this data.
Overall Participants	9
Age, Customized (participants) [Number]
Between 40 and 75 years	9 100%
Sex/Gender, Customized (participants) [Number]
Male and Female	9 100%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	The Change in Dynamic Hyperinflation Measured by End Expiratory Volumes Recorded by Optoelectronic Plethysmography (OEP).
Description	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.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

The principal investigator has left the institution. Attempts to contact the PI have been unsuccessful. Columbia will never have access to the data. Thus, data will not be analyzed. The only information available is the number of participants who started and completed the study, which was last reported to and approved by the IRB in February 2013.

Arm/Group Title	Active Medication or Placebo
Arm/Group Description	Data per arm is not available. Columbia will never have access to this data.
Measure Participants	0

2. Secondary Outcome

Title	Exercise Time in Steady State Exercise
Description	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.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

The principal investigator has left the institution. Attempts to contact the PI have been unsuccessful. Columbia will never have access to the data. Thus, data will not be analyzed. The only information available is the number of participants who started and completed the study, which was last reported to and approved by the IRB in February 2013.

Arm/Group Title	Active Medication or Placebo
Arm/Group Description	Data per arm is not available. Columbia will never have access to this data.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	The principal investigator has left the institution. Attempts to contact the PI have been unsuccessful. Columbia will never have access to the data. Thus, data will not be analyzed. The only information available is the number of participants who started and completed the study, which was last reported to and approved by the IRB in February 2013.
Arm/Group Title	Active Medication or Placebo
Arm/Group Description	Data per arm is not available. Columbia will never have access to this data.
All Cause Mortality
	Active Medication or Placebo
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Active Medication or Placebo
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Active Medication or Placebo
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.