Xenon MRI for Pulmonary Arterial Hypertension

(Jupiter PH Trial)

Overseen By David Ptashnik, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bastiaan Driehuys

Disqualifiers: Heart disease, Cancer, Sickle cell, 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: Unknown

Duration: 24 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are in Cohort 2, you must be either treatment naïve or have started treatment within the last 3 months.

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

Research shows that hyperpolarized 129Xe MRI can detect early changes in lung function related to pulmonary hypertension in animal models, suggesting it might help monitor the disease and assess treatment response in humans. ^{1 2 3 4 5}

How is the treatment 129Xe Hyperpolarized MRI different from other treatments for pulmonary arterial hypertension?

129Xe Hyperpolarized MRI is unique because it is a non-invasive imaging technique that allows doctors to see how well the lungs are working by assessing both ventilation (airflow) and gas exchange. Unlike traditional treatments that focus on managing symptoms, this method provides detailed images of lung function, which can help in diagnosing and monitoring the progression of pulmonary arterial hypertension. ^{3 4 5 6 7}

What is the purpose of this trial?

This trial uses a special MRI scan with a gas to monitor lung function in patients with severe lung disease. It targets those being monitored over time to better understand and track their condition. The MRI technique provides detailed lung function measurements and is well-tolerated, allowing for thorough exploration of lung function.

Research Team

Sudarshan Rajagopal, MD, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults aged 18-75 with Pulmonary Hypertension (PH), specifically those who are newly diagnosed or have started treatment within the last three months. Participants must be able to consent and follow the study schedule, and women of childbearing age need a negative pregnancy test before MRI scans. Those awaiting lung transplants can join too, but not if they have severe liver disease, heart issues, active cancer, sickle cell anemia or conditions preventing MRI use.

Inclusion Criteria

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

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

Women of childbearing potential must have a negative urine pregnancy test before MRI

Exclusion Criteria

Prisoners and pregnant women will not be approached for the study

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

I have sickle cell anemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 129Xe MRI scans and standard-of-care assessments including labs, echocardiography, and six-minute walk distance

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with 6-month follow-up appointments

5 years

Treatment Details

Interventions

• 129Xe Hyperpolarized

Trial Overview The trial is testing how a type of imaging called Xenon 129 Magnetic Resonance Imaging (MRI) can show changes in lung function and blood flow in patients with different types of Pulmonary Hypertension. It aims to understand how these images change with disease progression or after starting treatment.

Participant Groups

Group I: following pulmonary arterial hypertension subjects Experimental Treatment 1 Intervention

Following pulmonary arterial hypertension subjects upto 24 months

Group II: end-stage pulmonary hypertension . Experimental Treatment 1 Intervention

subjects with end-stage PH that currently on the waitlist for lung transplant

129Xe Hyperpolarized is already approved in United States for the following indications:

Approved in United States as Hyperpolarized 129Xe for:

• Pulmonary hypertension (investigational)

Who Is Running the Clinical Trial?

Bastiaan Driehuys

Lead Sponsor

Trials

15

Recruited

1,100+

Findings from Research

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 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]

This study is the first to use hyperpolarized 129Xe MRI to non-invasively assess pulmonary hypertension in a monocrotaline rat model, showing reduced gas exchange early in the disease and changes in tissue uptake later on.

The imaging results correlated well with histological findings, indicating that 129Xe MRI could be a valuable tool for monitoring disease progression and treatment response in pulmonary hypertension without the need for invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension. Virgincar, RS., Nouls, JC., Wang, Z., et al.[2021]

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 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]

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]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension. [2021]

4. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

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

Development of hyperpolarized noble gas MRI. [2019]

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

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