Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, aformoterol, Helium, Hyperpolarized helium, Hyperpolarized Noble Gas, MRI
Brief summary
The purpose of this study is to determine efficacy of MR imaging with hyperpolarized helium-3 gas in COPD patients both before and after treatment.
Detailed description
Hyperpolarized Helium Lung imaging has already been tested and proven to be scientifically possible in patients with a number of pulmonary disorders. However there is limited data on the sensitivity of this imaging technique, which would be essential for clinical use. This study is a double blinded study with two cohorts, each cohort being made up of patients with confirmed diagnosis of COPD. One group will receive a placebo while the other will receive treatment. A comparison of the data will resume once twenty patients have been consented and completed the study procedures.
Interventions
Patients will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the intervention (drug or placebo) will be administered and an hour will pass. Then three additional bags will be administered, again with five to ten minutes between each bag.
DRUGPlacebo
Subject will inhale a placebo (nebulized saline) with no drug.
DRUGAformoterol
Subjects will receive the drug arformoterol prior to scanning
Sponsors
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are male or female and are 50 years or older * Consent from the patient * Have been diagnosed with COPD * Must be able to hold their breath for up to 12 seconds * Must have a baseline FEV1 ≤ 80% of predicted but FEV1 \> 0.70 L * Must have a smoking history of 15 or more packs per year * Must have a breathlessness severity of ≥ 2 on the Medical Research Council dyspnea scale * Must be able to safely discontinue their respiratory medications for at least 12 hours.
Exclusion criteria
* Have any contraindications to an MR exam such as a pace-maker, metallic cardiac valves, magnetic material (i.e., surgical clips) implanted electronic infusion pumps or any other conditions that would preclude proximity to a strong magnetic field * Are undergoing the MR exam in an emergency situation * Are pregnant or become pregnant at any point within the study time. * People with psychiatric disorders will be excluded from the study. * Are claustrophobic and can not tolerate the imaging. * Uses supplemental oxygen * Have life-threatening or unstable respiratory status within 30 days before screening * Have a diagnosis of asthma and/or any chronic respiratory disease other than COPD * Have a lung resection greater than 1 full lobe * Have coronary artery disease or congestive heart failure * Are allergic to Arformoterol or similarly related drugs. * Are taking any of the drugs listed in the risks section and are unable to stop taking them.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Ventilation Volume | 2 hours | Subjects had hyperpolarized helium-3 MR scans completed before administration of an intervention and 2 hours after administration. These images were compared as described: The change in the total ventilation volume (Litres) measured in the hyperpolarized helium-3 MR image from pre-nebulizer inhalation to post-nebulizer inhalation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 | 2 hours | Spirometry was taken which measures FEV1 (in Litres), before administration of an intervention and again 2 hours after administration of an intervention. The change in FEV1 (Litres) from pre-nebulizer inhalation to post-nebulizer inhalation was compared. |
Countries
United States
Participant flow
Recruitment details
Patients with moderate to severe COPD were recruited and enrolled from the UMass Lung and Allergy Center from November 2008 to April 2011.
Participants by arm
| Arm | Count |
|---|---|
| Saline Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the placebo will be administered and an hour will pass. The placebo consists of a nebulized saline solution (2.1 mL). After administration of the placebo, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag. | 16 |
| Drug Subjects Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the drug aformoterol will be administered and an hour will pass. BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. After administration of the drug, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag. | 15 |
| Total | 31 |
Baseline characteristics
| Characteristic | Drug Subjects | Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 8 Participants | 15 Participants |
| Age Continuous | 68 years STANDARD_DEVIATION 11 | 63 years STANDARD_DEVIATION 7 | 66 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
Change in Total Ventilation Volume
Subjects had hyperpolarized helium-3 MR scans completed before administration of an intervention and 2 hours after administration. These images were compared as described: The change in the total ventilation volume (Litres) measured in the hyperpolarized helium-3 MR image from pre-nebulizer inhalation to post-nebulizer inhalation.
Time frame: 2 hours
Population: Analysis per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Subjects | Change in Total Ventilation Volume | 0.154317 Litres | Standard Deviation 0.512 |
| Brovana Subjects | Change in Total Ventilation Volume | -0.13687 Litres | Standard Deviation 0.306 |
Secondary
Change in FEV1
Spirometry was taken which measures FEV1 (in Litres), before administration of an intervention and again 2 hours after administration of an intervention. The change in FEV1 (Litres) from pre-nebulizer inhalation to post-nebulizer inhalation was compared.
Time frame: 2 hours
Population: As per protocol
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo Subjects | Change in FEV1 | -0.12 Litres | Standard Deviation 0.25 |
| Brovana Subjects | Change in FEV1 | 0.16 Litres | Standard Deviation 0.26 |