Hyperpolarized Xenon-129 MRI: a New Multi-dimensional Biomarker to Determine Pulmonary Physiologic Responses to COPD Therapeutics

Hyper polarized xenon-129 MRI (HXe MRI) is a unique imaging test which can detect how air is flowing in and out of lungs and how oxygen can move from inhaled air into the blood. Chronic Obstructive Pulmonary Disease (COPD) is a disease in which patients develop narrowing of airways, thus, having difficulties breathing air in and out their lungs and also damaging the lung tissues which patients need to move oxygen from the air into blood.

In this study, two drugs which are already approved by FDA (Anoro and Arnuity) will be administered to patients who are already known to have COPD. While patients are being treated with these two drugs (one drug at a time over a month), lung health by using usual testing methods (CT scan of the lung, pulmonary function test, and blood test) will be assessed in addition to HXe MRI.

The goal of this study is to prove that the HXe MRI is an excellent imaging test to show the state of lung health among COPD patients and also to obtain new informations on how lung health changes with drugs that are already approved by US FDA. This work is anticipated to help develop HXe MRI as a new clinical test which can guide how to treat patients with COPD and if new therapies can improve lung health of patients with COPD.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Anoro Ellipta; Drug: Arnuity Ellipta

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Keswick, Virginia, United States, 22947
      • Roselove NUNOO-ASARE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• post bronchodilator PFT spirometry FEV1/FVC < 70% predicted
• History of diagnosis of COPD
• History of alpha 1 anti-trypsin deficiency

Exclusion Criteria:

• previous diagnosis of asthma, interstitial lung disease, pulmonary vascular disease, inability to complete MRI or any of the assessment testings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All COPD Subjects; All subjects will be assessed with hyper polarized xenon-129 MRI, pulmonary function test, quality of life measures (BDI, TDI, SGRQ, CRQ, BODE, GOLD), and blood test. Intervention: All subjects will received Anoro one puff once a day for 30 days first, then 3 day washout, then Arnuity 250 microgram one puff twice a day for 30 days to complete the study.	Drug: Anoro Ellipta; inhaler approved by FDA (strength umeclidinium 65 microgram + vilanterol 25 microgram) One puff once a day for 30 days; Other Names: umeclidinium + vilanterol; Drug: Arnuity Ellipta; inhaler approved by FDA (strength 250 microgram) One puff twice a day for 30 days; Other Names: fluticasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the hyper polarized MRI xenon-129 MRI (HXe MRI) assessment pre-post 30-day treatment of umeclidinium+vilanterol or Flovent	In vivo lung physiology measurement obtained by HXe MRI pre and post drug intervention. In vivo lung physiology is measured by % of the lung that does not ventilate (dead space ventilation), among of the dissolved xenon-129 gas location among airways, interstitial tissues, or circulating red blood cells. These measures will be reported as continuous variables for data analyses.	Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High resolution CT of lung	Quantification of emphysematous lung tissues and abnormally thickened airways in correlation with changed detectable by HXe MRI. % of lung tissues with emphysema will be quantified by measuring tissue density using Hounsfield Unit (HU). Based on COPDgene and other studies, we will use HU < -950 as emphysematous lung tissue. The lung CT scan will then be processed to yield % of lung tissue with emphysema. The airway thickness will be measured by standardized imaging algorithm developed by VIDA imaging.	First baseline only=day 0
Changes in pulmonary Function Test (PFT) from pre to post-umeclidinium+vilanterol or Flovent	Measurement of in vivo lung physiology using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. The gas exchange capacity will be assessed by diffusion capacity of carbon monoxide represented as percent DLCO. This is a standard clinical measure being used routinely in pulmonary clinics.	Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in Baseline Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.	Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in Transient Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.	Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in Saint George's Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.	Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in Chronic Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.	Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in BODE score from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. BODE score is calculated by the results from the pulmonary function test, modified medical research council score, and body mass index. This will yield a score ranging from 0 to 10 with higher scores predicting higher chance of mortality.	Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
Changes in GOLD Stage from pre to post-umeclidinium+vilanterol or flovent	Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. GOLD stage is calculated by a combination of pulmonary function test result, modified medical research council score, and history of frequency of COPD exacerbation previous 12 months. This score will yield GOLD stages A (mild) to , B, C, D (most severe).	Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Kun Qing, PhD, University of Virginia; Principal Investigator: Yun M Shim, MD, University of Virginia

Publications and helpful links

General Publications

• Qing K, Ruppert K, Jiang Y, Mata JF, Miller GW, Shim YM, Wang C, Ruset IC, Hersman FW, Altes TA, Mugler JP 3rd. Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI. J Magn Reson Imaging. 2014 Feb;39(2):346-59. doi: 10.1002/jmri.24181. Epub 2013 May 16.
• Qing K, Mugler JP 3rd, Altes TA, Jiang Y, Mata JF, Miller GW, Ruset IC, Hersman FW, Ruppert K. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR Biomed. 2014 Dec;27(12):1490-501. doi: 10.1002/nbm.3179. Epub 2014 Aug 22.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2017
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimated): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: MRI; COPD; emphysema; chronic obstructive pulmonary disease; hyper polarized gas MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Dermatologic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 19569-19352

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: At the conclusion of the study, correlation data between COPD phenotypes and changes in MRI characteristics will be shared. Data from individuals will be complied with unique study-generated subject ID after removing all personal identifiers. Once this is completed, the data may be shared with hyper polarized MR imaging network currently being formed in collaboration with University of WI, U Penn, Duke, U of Cincinnati, and U Missouri. The data will be accessible by these investigators after the data sharing plans are reviewed by the IRB of the record (at the University of Virginia).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No