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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03002389
• Other study ID #: 19569-19352
• Status: Recruiting
• Phase: Phase 2
• Start date: November 5, 2017
• Est. completion date: January 31, 2025

Study information

• Verified date: May 2022
• Source: University of Virginia
• Contact: Roselove Asare, RT
• Phone: 4342436074
• Email: rnn3b[@]virginia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: January 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Anoro Ellipta
inhaler approved by FDA (strength umeclidinium 65 microgram + vilanterol 25 microgram) One puff once a day for 30 days
• Arnuity Ellipta
inhaler approved by FDA (strength 250 microgram) One puff twice a day for 30 days

Locations

Country	Name	City	State
United States	Roselove NUNOO-ASARE	Keswick	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. 2 — View Citation

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):3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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