Hyperpolarized 129Xe MRI for Pulmonary Arterial Hypertension

(PH SOLAR Trial)

Overseen By Sudarshan Rajagopal, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bastiaan Driehuys

Disqualifiers: Heart disease, Sarcoidosis, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6-8 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Hyperpolarized 129Xe MRI for Pulmonary Arterial Hypertension?

Research shows that Hyperpolarized 129Xe MRI can detect abnormalities in lung function, such as gas exchange issues, which are important in diagnosing and monitoring pulmonary vascular diseases. This suggests it could be useful in managing conditions like pulmonary arterial hypertension by providing detailed lung imaging. ^{1 2 3 4 5}

How does hyperpolarized 129Xe MRI differ from other treatments for pulmonary arterial hypertension?

Hyperpolarized 129Xe MRI is unique because it is an imaging technique rather than a traditional drug treatment. It allows doctors to see how well air moves through the lungs and how gases are exchanged in the blood, which can help in diagnosing and monitoring pulmonary arterial hypertension more effectively than standard imaging methods. ^{1 2 3 4 6}

What is the purpose of this trial?

The main goal of this study is to develop a noninvasive signature for pulmonary vascular remodeling in Group 3 PH patients, using hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI). Such a signature may identify Group 3 PH responders to PAH-specific therapies. PAH's unique 129Xe MRI signature has been shown in previous studies. Past studies have lacked a pathologic "ground truth" correlate of these signatures, which could be provided by comparing them with the pathology of lung explant tissue from patients who have undergone a lung transplant. This signature could be validated in a cohort of patients with Group 3 PH in future studies.

Research Team

Sudarshan Rajagopal, MD, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults over 18 with certain lung diseases like IPF or COPD, with or without high blood pressure in the lungs (PH). Participants must not have severe heart disease, active cancer, liver disease, sarcoidosis, sickle cell anemia, and should be able to undergo MRI scans. Pregnant women and prisoners are excluded.

Inclusion Criteria

Willing and able to give informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed)

I have been diagnosed with IPF and high blood pressure in the lungs.

I have been diagnosed with IPF without high blood pressure in the lungs.

Exclusion Criteria

Prisoners and pregnant women will not be approached for the study

My heart function is reduced (LVEF < 45%) or I have severe thickening of my heart walls.

I have been diagnosed with sarcoidosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline 129Xe MRI to establish initial pulmonary vascular remodeling signature

1 day

1 visit (in-person)

Treatment

Participants receive PAH-specific therapies and undergo 129Xe MRI to monitor changes in pulmonary vascular remodeling

6-8 weeks

2-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hyperpolarized 129Xe

Trial Overview The study tests a noninvasive imaging technique using hyperpolarized Xenon gas (129Xe) during MRI to detect changes in the lungs' blood vessels of patients with Group 3 Pulmonary Hypertension. It aims to find a signature that predicts response to specific therapies.

Participant Groups

Group I: PAH: Experimental Treatment 1 Intervention

Clinical diagnosis of PAH (Group 1 PH) in the absence of severe chronic lung disease, left heart disease, chronic thromboembolism, sarcoidosis, sickle cell disease or other causes of non-Group 1 PH.

Group II: IPF-noPH Experimental Treatment 1 Intervention

Clinical diagnosis of IPF in the absence of precapillary PH

Group III: IPF-PH Experimental Treatment 1 Intervention

Clinical diagnosis of IPF with precapillary PH

Group IV: COPD-noPH Experimental Treatment 1 Intervention

Clinical diagnosis of COPD in the absence of precapillary PH.

Group V: COPD-PH Experimental Treatment 1 Intervention

Clinical diagnosis of COPD with precapillary PH

Who Is Running the Clinical Trial?

Bastiaan Driehuys

Lead Sponsor

Trials

15

Recruited

1,100+

Findings from Research

Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is a new imaging technique that can assess both how well air moves in and out of the lungs (ventilation) and how effectively gases are transferred in the lungs.

While most studies have focused on non-cancer lung diseases, HP 129 Xe MRI shows great potential for improving the management and understanding of lung cancer by evaluating these key lung functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. Song, EJ., Kelsey, CR., Driehuys, B., et al.[2022]

Hyperpolarized 129Xe MRI is a new imaging technique that allows for detailed lung imaging and can also detect 129Xe in the brain, providing insights into brain parenchyma and blood vessels.

The study outlines specific protocols for using 129Xe MRI in both rodents and humans, highlighting its potential for advanced medical imaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. Chahal, S., Prete, BRJ., Wade, A., et al.[2019]

Hyperpolarized (HP) (129)Xe MRI effectively identified significant pulmonary vascular disease (PVD) in two patients who had normal ventilation but decreased gas transfer, despite inconclusive results from other imaging methods.

The technique shows promise for diagnosing PVD and monitoring treatment responses, but further research is needed to establish its sensitivity and specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease. Dahhan, T., Kaushik, SS., He, M., et al.[2023]

The study involving 13 healthy volunteers demonstrated that MRI measurements of gas exchange using hyperpolarized 129 Xenon show good repeatability, particularly for the RBC:Barrier ratio, which had a high intraclass correlation coefficient of 0.92.

The RBC:Barrier ratio was strongly correlated with intervisit changes in DLCO, indicating its potential as a reliable imaging biomarker for assessing pulmonary function, independent of lung inflation volume.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeatability of regional pulmonary functional metrics of Hyperpolarized 129 Xe dissolved-phase MRI. Hahn, AD., Kammerman, J., Evans, M., et al.[2020]

The study introduces a new method for delivering hyperpolarized (129)Xe gas directly into the arterial blood of live rats using an extracorporeal circuit, allowing for continuous infusion and improved imaging capabilities.

This technique enables high-resolution, 3D MRI of lung ventilation and perfusion, facilitating detailed studies of the ventilation-perfusion ratio and potentially expanding the use of (129)Xe for functional imaging in other body areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe. Cleveland, ZI., Möller, HE., Hedlund, LW., et al.[2021]

Hyperpolarized 129Xe MRI (HypX-MRI) shows great promise as a new diagnostic tool, enhancing the detectability of lung structures and potentially allowing for better imaging of lipid-rich tissues, which has been challenging with traditional methods.

This technique could help identify issues like ventilation-perfusion mismatch in pulmonary diseases and may also be used for functional MRI studies of the brain, opening new avenues for understanding lung function and brain perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. Albert, MS., Balamore, D.[2019]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Repeatability of regional pulmonary functional metrics of Hyperpolarized 129 Xe dissolved-phase MRI. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]