Xenon MRI in Stable Pulmonary Hypertension (Jupiter AUGEAN)

Xenon MRI in Stable Patients With Pulmonary Hypertension

The objective of this project is to determine how pulmonary vascular remodeling in Pulmonary Arterial Hypertension (PAH) at cellular and pathological level is associated with gas exchange physiology changes and hemodynamics (monitored with 129Xe MRI/MRS) and how these signals change with disease progression or treatment.

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Artery Hypertension
• Intervention / Treatment: Drug: Hyperpolarized Xe129

Detailed Description

The clinical and research need for noninvasive biomarkers in pulmonary arterial hypertension (PAH) has led the study team to develop 129Xe magnetic resonance imaging (129Xe MRI) to image pulmonary vascular pathology through quantitative 3D maps of gas transfer across the pulmonary blood-gas barrier. 129Xe MRI, in combination with 129Xe spectroscopy (MRS), has a unique signature in PAH and can simultaneously measure capillary blood volume and hemodynamic changes associated with pulmonary vascular remodeling (Wang '19a). This project aims to determine how pulmonary vascular remodeling in PAH at a cellular and pathological level is related to gas exchange physiology changes and hemodynamics (monitored with 129Xe MRI/MRS) and the change in these signals over one year in patients with "stable" PAH. Our central hypothesis is that patients with "stable" PAH will display persistent abnormalities on 129Xe MRI/MRS consistent with pulmonary vascular remodeling and that some patients may have worsening of their disease while appearing to be "stable" disease.

The study team will assess the ability of 129Xe MRI to longitudinally monitor disease progression in patients with "stable" PAH. First, the team will enroll "stable" PAH patients and obtain detailed clinical information to be stored in the REDCAP database. The study team will then follow this cohort of PAH subjects for one year, performing 129Xe MRI scans at baseline, 3 months, 6 months and one year in addition to their standard-of-care assessments including appointments labs, echo, and 6MWTs.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Ptashnik, MS; Phone Number: 919-668-2642; Email: david.ptashnik@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stable on current treatment regimen and not planning to undergo initiation of new therapy for at least 3 months
2. Outpatients of any gender, Age 18-75
3. WHO functional class (FC) 1-3 symptoms with a diagnosis of group 1 PH (mean pulmonary artery pressures (mPAP) > 20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg and pulmonary vascular resistance (PVR) ≥3 WU)
4. Willing and able to give informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed).

5. Women of childbearing potential must have a negative urine pregnancy test before MRI

   Exclusion Criteria:

6. Sarcoidosis
7. Active cancer
8. Sickle cell anemia
9. Liver disease (Childs-Pugh class C)
10. Any conditions that prevent the performance of 129Xe MRI scans.
11. Prisoners and pregnant women will not be approached for the study
12. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
13. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements

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: Patients with Stable Pulmonary Arterial Hypertension; Stable on current treatment regimen and not planning to undergo initiation of new therapy for at least 3 months Intervention: Drug: 129Xe Hyperpolarized	Drug: Hyperpolarized Xe129; Hyperpolarized Xenon Gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary vascular function	Measured by RBC/Membrane metrics on Xe MRI	Baseline, 3 months, 6 months, 1 year
Change in pulmonary vascular function	Measured by RBC shift metrics on Xe MRI	Baseline, 3 months, 6 months, 1 year
Change in pulmonary vascular functoin	Measured by RBC amplitude oscillation metrics on Xe MRI	Baseline, 3 months, 6 months, 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six Minute Walk Test Distance (6MWD)	Distance patient is able to walk during a six minute walk test	Baseline, 3 months, 6 months, 1 year
NTproBNP	Lab value of NTproBNP	Baseline, 3 months, 6 months, 1 year
World Health Organization (WHO) Functional Class (FC)	Change in Functional Class of Pulmonary Hypertension symptoms	Baseline, 3 months, 6 months, 1 year
Hopsitalizations	Frequency of hospitalizations	Baseline, 3 months, 6 months, 1 year

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Sudarshan Rajagopal, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 3, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: Pro00113235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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