Xenon MRI Pulm Hypertension

NCT ID: NCT04991454

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2026-08-30

Brief Summary

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.

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

Conditions

Pulmonary Hypertension; Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

end-stage pulmonary hypertension .

subjects with end-stage PH that currently on the waitlist for lung transplant

Group Type: OTHER

129Xe Hyperpolarized

Intervention Type: DRUG

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.

following pulmonary arterial hypertension subjects

Following pulmonary arterial hypertension subjects upto 24 months

Group Type: OTHER

129Xe Hyperpolarized

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bastiaan Driehuys

OTHER

Sponsor Role: lead

Responsible Party

Bastiaan Driehuys

Associate Professor of Radiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sudarshan Rajagopal, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Claudia Salazar

Role: CONTACT

claudia.salazar@duke.edu

+1 919 660 2026

Facility Contacts

David Ptashnik

Role: primary

david.ptashnik@duke.edu

919-668-2642

Other Identifiers

Pro00107613

Identifier Type: -

Identifier Source: org_study_id