129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)

Phase 2

Recruiting

• Conditions: Pulmonary Arterial Hypertension; Idiopathic Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension Associated With Connective Tissue Disease (Disorder); Connective Tissue Diseases
• Interventions: Drug: 129Xe Hyperpolarized

• Registration Number: NCT06104228
• Lead Sponsor: Bastiaan Driehuys

Brief Summary

The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD).

Detailed Description

Subject Enrollment This study will consent and enroll 20 subjects total.

• For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled.

Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints.

Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months

Secondary Study Endpoints

There will be several secondary endpoints for this trial:

* Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months

* Change in 6MWD from baseline to 12 months

* Change in NTproBNP from baseline to 12 months

* Change in WHO FC from baseline to 12 months

Primary Safety Endpoints

There will be several primary safety endpoints for this trial:

* Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE)

* Withdrawals due to adverse event or death

* Incidence of Adverse Events of Significant Interest (AESI):

* Electrocardiogram and any findings

* Physical examination and vital signs

Study Timeline

• Study First Submitted: 2023-10-23
• Study First Submitted QC: 2023-10-23
• Study First Posted: 2023-10-27
• Study Start: 2024-08-12
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2026-01-01
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Arm 1 -IPAH

• Age: 18-75 years
• WHO functional class 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 Wood Units (WU)
• No other cause identified for PAH

Arm 2 -PAH-CTD

• Age: 18-75 years
• WHO functional class (FC) 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 WU
• Diagnosis of connective tissue disease

Exclusion Criteria

• PH other than Idiopathic PAH or PAH associated with CTD; any conditions that prevent the performance of 129Xe MRI scans will be excluded from the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Idiopathic Pulmonary Arterial Hypertension	129Xe Hyperpolarized	Arm 1... patients with IPAH
Pulmonary Arterial Hypertension Associated with Connective Tissue Disease	129Xe Hyperpolarized	Arm 2... patients with CTD-PAH

Primary Outcome Measures

Name	Time	Method
Pulmonary Vascular Remodeling	1 year	The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months

Secondary Outcome Measures

Name	Time	Method
RBC Oscillation Amplitude	1 year	• Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months
6 Minute Walk Distance	1 Year	Change in 6MWD from baseline to month 12
NTproBNP	1 year	Change in NTproBNP from baseline to month 12
World Health Organization (WHO) Functional Class (FC)	1 year	Change in WHO FC from baseline to month 12

Trial Locations

Locations (1)

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