Assessment of Arformoterol for Chronic Obstructive Pulmonary Disease (COPD) Using Hyperpolarized 3He MRI

Not Applicable

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Hyperpolarized Helium-3
Drug: Aformoterol
Drug: Placebo

Registration Number: NCT00846287

Lead Sponsor: University of Massachusetts, Worcester

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drug Subjects	Hyperpolarized Helium-3	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 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.
Saline	Hyperpolarized Helium-3	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 placebo (nebulized saline solution) will be administered (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.
Drug Subjects	Aformoterol	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 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.
Saline	Placebo	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 placebo (nebulized saline solution) will be administered (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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.