Xenon MRI for Idiopathic Pulmonary Fibrosis

Overseen By Matthew P Kummerer, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Pirfenidone, Nintedanib

Disqualifiers: Pregnancy, Cardiac arrhythmia, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

34 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is being done to determine whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Idiopathic Pulmonary Fibrosis (IPF) patients receiving approved IPF treatments. Subjects will undergo an approximately hour long comprehensive MRI protocol, including administration of multiple doses of hyper-polarized 129 Xenon. The subjects will have this initial study prior to initiation of IPF therapies. Then the subjects will have repeat studies at 3, 6 and 12 months following the initiation of therapy. Additional studies including pulmonary function studies, serum for bio markers, 6 minute walk distance and a high-resolution computed tomography (HRCT) scan (only at the 6 month visit) will be performed to determine how 129 Xenon MRI performs relative to standard of care evaluations for IPF. The MRI uses a magnet and radio waves to make diagnostic medical images of the body. There have been no ill effects reported from exposure to the magnetism or radio waves used in this test. Risks of the xenon gas are slight numbness in legs, nausea, a feeling of well-being, and mild tingling in fingertips. You will have pulmonary function testing for the study, you may experience breathlessness or dizziness during or immediately following these tests.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be new to IPF treatments like nintedanib or pirfenidone.

What data supports the effectiveness of the treatment Hyperpolarized 129 Xenon Gas for idiopathic pulmonary fibrosis?

Research shows that Hyperpolarized 129 Xenon MRI can effectively image lung function and detect impaired lung physiology in idiopathic pulmonary fibrosis (IPF). It provides detailed images of how gas moves through the lungs, which can help monitor disease progression and assess treatment response. ^{1 2 3 4 5}

Is hyperpolarized 129 Xenon gas safe for use in humans?

Research shows that hyperpolarized 129 Xenon gas has been used safely in both healthy volunteers and people with lung diseases for MRI imaging. It is considered tolerable and has been studied for its ability to help visualize lung function without significant safety concerns. ^{1 5 6 7 8}

How does Xenon MRI differ from other treatments for idiopathic pulmonary fibrosis?

Xenon MRI is unique because it uses hyperpolarized xenon-129 gas as a contrast agent to provide detailed images of lung function, specifically assessing ventilation and gas transfer, which is not possible with standard imaging techniques. This approach offers a novel way to evaluate lung physiology in patients with idiopathic pulmonary fibrosis, potentially identifying issues that other treatments might miss. ^{1 2 8 9 10}

Research Team

Robert Tighe, MD

Principal Investigator

Duke University Health Systems

Eligibility Criteria

This trial is for adults over 18 with a clinical diagnosis of Idiopathic Pulmonary Fibrosis (IPF) who haven't started treatment. They must be able to consent and follow the study schedule. People can't join if they don't fit in the MRI coil, have had cardiac issues or severe respiratory illness recently, are pregnant, need supplemental oxygen, or have conditions affecting their ability to participate.

Inclusion Criteria

I am over 18 years old and not hospitalized.

I have been diagnosed with IPF and have not started treatment with nintedanib or pirfenidone.

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

Exclusion Criteria

I have had a heart rhythm problem in the last month.

I haven't had a lung infection in the last 30 days.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline MRI

Participants undergo a comprehensive MRI protocol using hyper-polarized 129 Xenon gas prior to initiation of IPF therapies

1 hour

1 visit (in-person)

Treatment and Monitoring

Participants receive approved IPF treatments and undergo repeat MRI studies at 3, 6, and 12 months, along with additional pulmonary function studies and biomarker assessments

12 months

3 visits (in-person) at 3, 6, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hyperpolarized 129 Xenon Gas

Trial Overview The study tests if MRI scans using hyperpolarized 129 Xenon gas can track lung function changes in IPF patients over time compared to standard treatments. Participants will undergo MRIs before starting therapy and at intervals up to one year after beginning treatment.

Participant Groups

Group I: Newly Diagnosed Idiopathic Pulmonary Fibrosis (IPF) Experimental Treatment 1 Intervention

Whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Idiopathic Pulmonary Fibrosis (IPF) patients receiving approved IPF treatments

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

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 xenon-129 MRI detected significant lung function impairments in patients with usual interstitial pneumonia (UIP), showing a ventilation defect fraction of 30% compared to 21% in healthy controls, indicating its efficacy in identifying lung abnormalities.

The MRI also revealed elevated levels of xenon dissolved in the lung interstitium in UIP patients, which could serve as an early indicator of lung fibrosis, even when traditional pulmonary function tests showed normal or mild impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis. Qing, K., Altes, TA., Mugler, JP., et al.[2023]

Hyperpolarized 129Xe MRI effectively identifies functional impairment in patients with idiopathic pulmonary fibrosis (IPF), showing a significant increase in barrier uptake compared to healthy individuals, indicating its potential as a diagnostic tool.

The MRI metrics correlated strongly with pulmonary function tests (PFTs) but poorly with CT fibrosis scores, suggesting that 129Xe MRI may provide a more accurate assessment of lung function and disease progression in IPF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis. Wang, JM., Robertson, SH., Wang, Z., et al.[2018]

Hyperpolarized (HP) noble gas MRI, particularly using 129Xe, has shown promising results in assessing lung ventilation and regional lung physiology, making it a potential game-changer in pulmonary medicine.

Despite being limited to select academic institutions currently, advancements in polarizer technology suggest that HP 129Xe MRI could soon become more widely available for clinical use, enhancing the diagnostic capabilities for lung conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. Ebner, L., Kammerman, J., Driehuys, B., et al.[2018]

Hyperpolarized noble gas MRI using helium-3 or xenon-129 enhances MRI signal, making it a promising method for imaging lung function and ventilation.

While there are safety considerations and challenges in clinical application, this technology holds potential for better understanding lung microstructure and function in various pulmonary diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary hyperpolarized noble gas MRI: recent advances and perspectives in clinical application. Liu, Z., Araki, T., Okajima, Y., et al.[2017]

Inhalation of hyperpolarized (129)Xe gas was well tolerated among 42 participants, including healthy individuals and those with various pulmonary diseases, with only two mild adverse events reported, indicating a strong safety profile.

The study showed that while there were statistically significant changes in oxygen saturation and heart rate after inhalation, these changes were clinically insignificant and resolved quickly, suggesting that (129)Xe inhalation is safe for use in both healthy and diseased lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Shukla, Y., Wheatley, A., Kirby, M., et al.[2022]

A new continuous-flow system for producing hyperpolarized xenon (129Xe) has been developed, achieving production rates of 0.3 liters per hour with 64% polarization, significantly improving the availability of this imaging agent for lung MRI studies.

This technology allows for the production of multiliter quantities of hyperpolarized xenon several times daily, enabling more extensive human lung imaging studies that were previously limited by the availability of hyperpolarized gas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. Hersman, FW., Ruset, IC., Ketel, S., et al.[2022]

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. Australia pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis. [2023]

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

Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Pulmonary hyperpolarized noble gas MRI: recent advances and perspectives in clinical application. [2017]

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

Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. [2022]

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

Large production system for hyperpolarized 129Xe for human lung imaging studies. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

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

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