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Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI

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ClinicalTrials.gov Identifier: NCT03367312
Recruitment Status : Suspended (suspended for this protocol due to the pandemic,)
First Posted : December 8, 2017
Last Update Posted : May 20, 2020
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
Bastiaan Driehuys, Duke University

Brief Summary:
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI techniques for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated too test gas exchange dynamics with high temporal resolution. The conventional 1H MRi scans will include a free-breathing ultra-short echo time scan that provides images similar to that of a CT scan. This will be done pre, immediately post, and 2-4 hours post inhaled prostacyclin therapy.

Condition or disease Intervention/treatment Phase
Pulmonary Vascular Disease Drug: Hyperpolarized 129Xenon gas Phase 2

Detailed Description:

This study seeks to determine whether hyperpolarized 129Xenon MRI can detect improvements in pulmonary gas exchange in patients with Group 1 and 3 PH treated with iTRE. We will associate this with changes in serum concentrations of treprostinil and levels of peripheral vasodilation. This work seeks to apply and test a novel non-invasive methodology, hyperpolarized (HP) 129Xenon (Xe) magnetic resonance imaging (MRI), for the diagnosis of Pulmonary Vascular Disease. Hyperpolarized 129Xe MRI has been under active development and used in clinical research at Duke for over 7 years. If successful, 129Xe MRI could overcome the current limitations of PVD diagnosis while conferring a number of potential benefits. First, imaging the abnormalities in the lungs allows the diagnosis of PVD in the setting of concomitant heart or lung disease. With HP 129Xe MRI, abnormalities in gas exchange secondary to PVD can be directly visualized. Second, non-invasive diagnosis of PVD could remove the need for an invasive RHC. While RHC is a relatively safe procedure, there are a number of limitations to the interpretation of RHC, including arbitrary cutoffs for mPAP, PCWP, and PVR. Third, the abnormalities on HP 129Xe MRI could be used to non-invasively monitor response to therapy. If we are successful in demonstrating the applicability of HP 129Xe MRI, this technology holds the promise of greatly improving the diagnosis and management of PVD.

This study will enroll ten patients with pulmonary hypertension (PH). The ten patients will be World Health Organization (WHO) PH classification Group 1 or out-of-proportion Group 3, with lung disease. These patient have been inhaled treprostinil (iTRE) as standard of care for their PH. Inhaled treprostinil (iTRE) is an FDA approved medication under the brand name of Tyvaso. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. The medication is delivered noninvasively, directly to the lungs using the approved ultrasonic nebulizer delivery system. Patients will take the inhaled treatment four times a day, about every four hours.

The iTRE will be used to characterize their 129Xe MRI imaging, peripheral vasodilation and serum treprostinil concentration before and after treatment with iTRE. As iTRE has a plasma concentration half-life of ~ 45 minutes and time-to-peak concentration of 15 minutes, imaging done immediately before, 15 minutes after and 2-4 hours after drug treatment would potentially allow the visualization of changes in gas diffusion and peripheral vasodilation associated with iTRE. This is similar to changes seen in changes in ventilation in asthma after treatment with bronchodilators. Monitoring a later time point would also allow us to test whether vasodilation persists in the lung vasculature compared to the peripheral circulation. This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI techniques for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This will be a single-blinded open-label study enrolling 15 patients (accrued 12 subjects total) with Pulmonary Hypertension who are currently on a stable dose of Inhaled Prostacyclin for treatment of PH.
Masking: None (Open Label)
Masking Description: The outcomes assessor, the radiologist who is reading the imaging will be blinded to treatment.
Primary Purpose: Diagnostic
Official Title: Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pulmonary Hypertension Patients on Inhaled Prostacyclin
10 subjects will Pulmonary Hypertension on a stable dose of Inhaled Prostacyclin for treatment of PH.
Drug: Hyperpolarized 129Xenon gas
Hyperpolarized 129Xenon gas XeMRI scans will provide 3D images of ventilation and gas exchange pre, post, and 2-4 hours post inhaled prostacyclin treatment. Subjects will inhale HP 129Xe from the dose delivery bags with each scan and then move into the scanner and undergo basic 1H localizer and anatomical scans. Once localization is complete, subjects will undergo several MRI scans after inhalation of HPXe. This will occur as three scans at the three different time points (pre, post, and 2-4 hours post) of inhaled prostacyclin treatment.
Other Name: Xe MRI




Primary Outcome Measures :
  1. Diagnostic accuracy as measured by ROC analysis [ Time Frame: 2 weeks ]
    Determine diagnostic accuracy of XeMRI in detection in improvement in pulmonary gas exchange in patient with PH Group 1 and 3 treated with inhaled prostacyclin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with known Pulmonary Hypertension on treatment with inhaled prostacyclin (iTRE) that are followed in the Duke Pulmonary Vascular Disease Clinic. Inclusion criteria includes: Group 1 PH (mPAP ≥ 25 mmHg, PCWP ≤ 15 mmHg in the absence of significant concomitant left heart disease or lung disease), out-of-proportion Group 3 PH (mPAP ≥ 25 mmHg, PCWP ≤ 15 mmHg with PVR ≥ 5 WU and evidence of right heart failure in the setting of lung disease), maintenance on a stable, well-tolerated treatment dose of iTRE (ideally ≥ 8 breaths QID). Pregnant women will be excluded from this study. Women of childbearing potential must have a negative urine pregnancy test in order to participate on this study.

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03367312


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Bastiaan Driehuys
United Therapeutics
Investigators
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Principal Investigator: Sudarshan Rajagopal, MD, PhD Duke University
Study Director: Bastiann Driehays, PhD Duke University
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Responsible Party: Bastiaan Driehuys, Professor, Duke University Medical Center, Duke University
ClinicalTrials.gov Identifier: NCT03367312    
Other Study ID Numbers: Pro00086282
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Xenon
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs