Hyperpolarized 129Xe MRI for Imaging Pulmonary Function

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Duke University
Sponsor:
Information provided by (Responsible Party):
Bastiaan Driehuys, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01280994
First received: January 9, 2011
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to develop and evaluate the usefulness of MRI using 129Xe gas for regional assessment of pulmonary function. Specifically, three forms of 129Xe MRI contrast will be the investigators focus — 1) imaging of the 129Xe ventilation distribution, 2) imaging the alveolar microstructure via the 129Xe apparent diffusion coefficient (ADC), and 3) imaging 129Xe that dissolves in the pulmonary blood and tissues upon inhalation. Such imaging of 129Xe gas transfer is expected to be uniquely sensitive to pathologies affecting gas exchange (fibrosis, emphysema, pulmonary hypertension) and provide new insights regarding the normal resting heterogeneity of pulmonary gas exchange.


Condition Intervention Phase
Asthma
Chronic Obstructive Pulmonary Disease
Interstitial Lung Disease
Cystic Fibrosis
Pulmonary Hypertension
Drug: Xenon
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Hyperpolarized 129Xe MR Imaging of the Lung Function in Healthy Volunteers and Subjects With Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The purpose of this trial is to examine the ability of HP 129Xe imaging to characterize the lung in healthy and diseased states. The safety endpoint for each subject is to record any adverse events as a measure of safety and tolerability. The technical endpoint for each subject is the acquisition of technically adequate HP 129Xe MR images.


Estimated Enrollment: 160
Study Start Date: January 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Xenon

    Each subject will receive up to but not exceeding 5 doses of hyperpolarized 129Xenon gas during any given imaging session. One of these doses is used for calibrating the MRI scanner and will contain 200 ml Xe, and 800ml N2. Xenon Doses used for image acquisition will contain up to 100% xenon at a volume up to 1 liter. Subjects will receive no more than 4 doses consisting of 100% xenon at 1 liter.

    Xenon will be administered with at least a 10 minute interval between doses to ensure that there is no imaging or health effect from residual xenon

Detailed Description:

Non-invasive imaging of pulmonary function is expected to provide critical insights that are needed to spur progress in characterizing and treating chronic pulmonary diseases. The current primary diagnostic measure is pulmonary function testing (PFT), which was introduced in the mid-19th century, yet remains the standard of care today. PFTs have the advantage of being non-invasive and widely available, but suffer from poor sensitivity and high variability. Thus, PFTs are ineffective in assessing therapeutic response or disease progression on reasonable time scales, given the frequent heterogeneity of disease and the lung's compensatory mechanisms.

It has long been appreciated that improving sensitivity requires assessing the lungs regionally. To this end, methods, such as computed tomography (CT), provide insights into lung structure, but lung function must be inferred. However, of greater concern is the high radiation dose associated with CT, which precludes frequent longitudinal follow-up imaging. Alternatively, regional imaging of both ventilation and perfusion is possible using nuclear medicine techniques such as planar scintigraphy, single photon computed tomography (SPECT), or positron emission tomography (PET). However, as with CT imaging, all these modalities expose the subject to ionizing radiation and cannot be applied serially without a compelling clinical need. Moreover, these nuclear imaging modalities suffer from poor spatial and temporal resolution.

The key role for HP 129Xe MRI is that it can enable non-invasive high-resolution imaging of all aspects of pulmonary structure and function. We have recently shown HP 129Xe MRI to visualize pulmonary ventilation with high resolution, as well as the ability to show abnormalities of the alveolar microstructure that are associated with the emphysema phenotype of COPD. We have also demonstrated the fundamentally new capability to directly visualize the uptake of 129Xe into the pulmonary capillary blood and tissues, which can provide an even more complete picture of pulmonary function by supplying regional gas exchange information.

Xenon is a noble gas that is not chemically altered by the body. A small fraction of the inhaled Xe is absorbed into the blood stream and has documented anesthetic effects at moderate concentrations. The levels of gas used in this protocol are within the previously derived safe limits for both animals and humans. The stable isotope 129Xe can be hyperpolarized, which is a means to enhance its gross MRI signal by a factor of ∼100,000. Such signal enhancement makes it possible to image the inhaled gas with high spatial and temporal resolution. Moreover, the properties of 129Xe enable images to be acquired with multiple forms of contrast including ventilation, lung microstructure, and regional gas exchange. Because 129Xe MRI uses no ionizing radiation, and only an inhaled gas contrast agent, it has the potential to be used in longitudinal studies to test the effects of therapy or monitor progression of disease noninvasively.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion Criteria for Healthy Control Subjects

  1. Subject has no diagnosed pulmonary conditions
  2. Subject has not smoked in the previous 5 years.
  3. Smoking history, if any, is less than or equal to 5 pack-years.

Inclusion Criteria for Subjects with lung disease

  1. Subject has a diagnosis of pulmonary dysfunction made by a physician
  2. No acute worsening of pulmonary function in the past 30 days

Exclusion Criteria:

  1. Subject is less than 18 years old
  2. MRI is contraindicated based on responses to MRI screening questionaire
  3. Subject is pregnant or lactating
  4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI
  5. Subject has received an investigational medicinal product (not including 129Xe) within 30 days of MRI
  6. Subject has any form of known cardiac arrhythmia
  7. Subject does not fit into 129Xe vest coil used for MRI
  8. Subject cannot hold his/her breath for 15 seconds
  9. Subject deemed unlikely to be able to comply with instructions during imaging
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01280994

Contacts
Contact: Jane Stiles, BS 919-668-3135 janev.stiles@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: Bastiaan Driehuys, Ph.D         
Principal Investigator: Holman P McAdams, MD         
Sponsors and Collaborators
Bastiaan Driehuys
  More Information

Publications:
Responsible Party: Bastiaan Driehuys, Associate Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01280994     History of Changes
Other Study ID Numbers: Pro00025110
Study First Received: January 9, 2011
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Lung Disease
Pulmonary Disease
Diagnostic Imaging
MRI

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Interstitial
Lung Diseases, Obstructive
Asthma
Cystic Fibrosis
Fibrosis
Hypertension
Hypertension, Pulmonary
Respiration Disorders
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pancreatic Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Xenon
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014