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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Connective Tissue Diseases, Pulmonary Arterial Hypertension, Idiopathic Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension Associated With Connective Tissue Disease (Disorder)

Intervention / Treatment
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* Drug: 129Xe Hyperpolarized


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Idiopathic Pulmonary Arterial Hypertension<br>Arm 1... patients with IPAH | Drug: 129Xe Hyperpolarized<br>* Each xenon dose will be limited to a volume less than 25% of a subject's total lung capacity (TLC), as is the case for all protocols currently carried out under IND 109490<br>|
| Other: Pulmonary Arterial Hypertension Associated with Connective Tissue Disease<br>Arm 2... patients with CTD-PAH | Drug: 129Xe Hyperpolarized<br>* Each xenon dose will be limited to a volume less than 25% of a subject's total lung capacity (TLC), as is the case for all protocols currently carried out under IND 109490<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Vascular Remodeling | 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 | 1 year | 

Secondary Outcome Measures

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