Xenon MRI Pulm Hypertension (Jupiter PH)

Xenon MRI in Pulmonary Hypertension

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Hypertension
• Intervention / Treatment: Drug: 129Xe Hyperpolarized

Detailed Description

In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the team will hypothesize are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects

In aim 3, The study team will test whether directly monitoring lung pathology with 129Xe MRI will provide additional prognostic information to standard-of-care clinical monitoring in 45 subjects (cohort 2). At 6-month follow-up appointments, standard-of-care assessments including labs, echocardiography, and six-minute walk distance and 129Xe MRI will be collected. The study team expect that In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the study team hypothesizes are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single-cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: David Ptashnik; Phone Number: 919-668-2642; Email: david.ptashnik@duke.edu
      • Principal Investigator: Sudarshan Rajagopal, MD
      • Sub-Investigator: Bastiann Driehays, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria of Cohort 1

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

1. Outpatients of either gender, Age 18-75
2. Awaiting a lung transplant
3. Diagnosis of precapillary PH (right heart catheterization demonstrating hemodynamic criteria of a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, pulmonary vascular resistance ≥ 3 WU, pulmonary capillary wedge pressure ≤ 15 mmHg) in the setting of Group 1 (PAH), 3 (PH due to chronic lung disease, 4 (PH due to pulmonary artery obstructions), or 5 (PH due to miscellaneous causes)
4. Willing and giving 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 of Cohort 1

Subjects presenting with any of the following will not be included in the trials:

1. Moderate to severe heart disease (LVEF <45%, Severe LV hypertrophy, Moderate to severe valvular disease)
2. PH due to schistosomiasis
3. Active cancer
4. Sickle cell anemia
5. Prisoners and pregnant women will not be approached for the study
6. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
7. 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

Inclusion Criteria of Cohort 2

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

1. Treatment naïve or treatment started within the last 3 months
2. Outpatients of either gender, Age 18-75
3. WHO functional class (FC) 2-3 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 of Cohort 2

Subjects presenting with any of the following will not be included in the trials:

1. Sarcoidosis
2. Active cancer
3. Sickle cell anemia
4. Liver disease (Childs-Pugh class C)
5. Any conditions that prevent the performance of 129Xe MRI scans.
6. Prisoners and pregnant women will not be approached for the study.
7. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine).
8. 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: end-stage pulmonary hypertension .; subjects with end-stage PH that currently on the waitlist for lung transplant	Drug: 129Xe Hyperpolarized; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC), as is the case for all protocols currently carried out under IND 109,490.
Other: following pulmonary arterial hypertension subjects; Following pulmonary arterial hypertension subjects upto 24 months	Drug: 129Xe Hyperpolarized; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC), as is the case for all protocols currently carried out under IND 109,490.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pulmonary vascular remodeling	The study team will determine whether the correlation between Red Blood Cell Signal from Xenon MRI to pathologic scoring of pulmonary vascular remodeling from histopathology is statistically significant.	5 years
Red Blood Cell Signal from Xenon MRI	We will determine whether the correlation between Red Blood Cell Signal from Xenon MRI to six minute walk distance, tricuspid annular plane excursion and right ventricular systolic pressure in longitudinal follow-up of PAH patients is statistically significant.	5 years

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Investigators: Principal Investigator: Sudarshan Rajagopal, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Xenon; Lung Transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: Pro00107613

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