Pulmonary Artery Hypertension
Conditions
Brief summary
The objective of this project is to determine how pulmonary vascular remodeling in Pulmonary Arterial Hypertension (PAH) at cellular and pathological level is associated with gas exchange physiology changes and hemodynamics (monitored with 129Xe MRI/MRS) and how these signals change with disease progression or treatment.
Detailed description
The clinical and research need for noninvasive biomarkers in pulmonary arterial hypertension (PAH) has led the study team to develop 129Xe magnetic resonance imaging (129Xe MRI) to image pulmonary vascular pathology through quantitative 3D maps of gas transfer across the pulmonary blood-gas barrier. 129Xe MRI, in combination with 129Xe spectroscopy (MRS), has a unique signature in PAH and can simultaneously measure capillary blood volume and hemodynamic changes associated with pulmonary vascular remodeling (Wang '19a). This project aims to determine how pulmonary vascular remodeling in PAH at a cellular and pathological level is related to gas exchange physiology changes and hemodynamics (monitored with 129Xe MRI/MRS) and the change in these signals over one year in patients with stable PAH. Our central hypothesis is that patients with stable PAH will display persistent abnormalities on 129Xe MRI/MRS consistent with pulmonary vascular remodeling and that some patients may have worsening of their disease while appearing to be stable disease. The study team will assess the ability of 129Xe MRI to longitudinally monitor disease progression in patients with stable PAH. First, the team will enroll stable PAH patients and obtain detailed clinical information to be stored in the REDCAP database. The study team will then follow this cohort of PAH subjects for one year, performing 129Xe MRI scans at baseline, 3 months, 6 months and one year in addition to their standard-of-care assessments including appointments labs, echo, and 6MWTs.
Interventions
Hyperpolarized Xenon Gas
Sponsors
Regeneron Pharmaceuticals
Bastiaan Driehuys
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Stable on current treatment regimen and not planning to undergo initiation of new therapy for at least 3 months 2. Outpatients of any gender, Age 18-75 3. WHO functional class (FC) 1-3 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
6. Sarcoidosis 7. Active cancer 8. Sickle cell anemia 9. Liver disease (Childs-Pugh class C) 10. Any conditions that prevent the performance of 129Xe MRI scans. 11. Prisoners and pregnant women will not be approached for the study 12. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine) 13. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pulmonary vascular function | Baseline, 3 months, 6 months, 1 year | Measured by RBC/Membrane metrics on Xe MRI |
| Change in pulmonary vascular functoin | Baseline, 3 months, 6 months, 1 year | Measured by RBC amplitude oscillation metrics on Xe MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Six Minute Walk Test Distance (6MWD) | Baseline, 3 months, 6 months, 1 year | Distance patient is able to walk during a six minute walk test |
| NTproBNP | Baseline, 3 months, 6 months, 1 year | Lab value of NTproBNP |
| World Health Organization (WHO) Functional Class (FC) | Baseline, 3 months, 6 months, 1 year | Change in Functional Class of Pulmonary Hypertension symptoms |
| Hopsitalizations | Baseline, 3 months, 6 months, 1 year | Frequency of hospitalizations |
Outcome results
None listed