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

Assessment of Arformoterol for COPD Using Hyperpolarized 3He MRI

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Hyperpolarized Helium-3; Drug: Aformoterol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States
      • UMASS Medical School Advanced MRI Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Drug Subjects; 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.	Drug: 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 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.; Other Names: HP 3He; Drug: Aformoterol; Subjects will receive the drug arformoterol prior to scanning; Other Names: Brovana
Placebo Comparator: Saline; 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: 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 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.; Other Names: HP 3He; Drug: Placebo; Subject will inhale a placebo (nebulized saline) with no drug.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 hours

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: February 16, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (Estimate): February 18, 2009

Study Record Updates

• Last Update Posted (Estimate): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 3, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: MRI; COPD; Helium; aformoterol; Hyperpolarized helium; Hyperpolarized Noble Gas
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: Docket # 12830