Xenon MRI Pulm Hypertension

Phase 2

Recruiting

• Conditions: Pulmonary Hypertension; Pulmonary Arterial Hypertension
• Interventions: Drug: 129Xe Hyperpolarized

• Registration Number: NCT04991454
• Lead Sponsor: Bastiaan Driehuys

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

Study Timeline

• Study First Submitted: 2021-07-07
• Study First Submitted QC: 2021-07-27
• Study First Posted: 2021-08-05
• Study Start: 2021-09-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-14
• Primary Completion: 2026-08-30
• Study Completion: 2026-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
following pulmonary arterial hypertension subjects	129Xe Hyperpolarized	Following pulmonary arterial hypertension subjects upto 24 months
end-stage pulmonary hypertension .	129Xe Hyperpolarized	subjects with end-stage PH that currently on the waitlist for lung transplant

Primary Outcome Measures

Name	Time	Method
pulmonary vascular remodeling	5 years	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.
Red Blood Cell Signal from Xenon MRI	5 years	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.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States