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

Purpose

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.

Condition	Intervention
Chronic Obstructive Pulmonary Disease	Drug: Hyperpolarized Helium-3 Drug: Placebo Drug: Aformoterol

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Diagnostic
Official Title:	Assessment of Arformoterol for COPD Using Hyperpolarized 3He MRI

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease) Gas

Drug Information available for: Formoterol fumarate Formoterol Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:

Change in Total Ventilation Volume [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
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:

Change in FEV1 [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
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.

Enrollment:	16
Study Start Date:	November 2008
Study Completion Date:	April 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: HP 3He Drug: Aformoterol Subjects will receive the drug arformoterol prior to scanning Other Name: 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 Name: HP 3He Drug: Placebo Subject will inhale a placebo (nebulized saline) with no drug. Other Name: Saline

Arms

Assigned Interventions

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 Name: HP 3He

Drug: Aformoterol

Subjects will receive the drug arformoterol prior to scanning

Other Name: 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 Name: HP 3He

Drug: Placebo

Subject will inhale a placebo (nebulized saline) with no drug.

Other Name: Saline

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.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846287

Locations

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

Sponsors and Collaborators

University of Massachusetts, Worcester

Investigators

Principal Investigator:

Mitchell S Albert, Ph.D.

UMASS Medical School

More Information

No publications provided

Responsible Party:	Mitchell Albert, Director of Advanced MRI Center, UMASS Medical Sch, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:	NCT00846287 History of Changes
Other Study ID Numbers:	Docket # 12830
Study First Received:	February 16, 2009
Results First Received:	June 19, 2012
Last Updated:	October 3, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Massachusetts, Worcester:

COPD
aformoterol
Helium

Hyperpolarized helium
Hyperpolarized Noble Gas
MRI

Additional relevant MeSH terms:

Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Formoterol
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013