129Xe MRI for Lung Disease

Overseen By Bastiaan Driehuys, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bastiaan Driehuys

Disqualifiers: Pregnancy, Cardiac arrhythmia, Respiratory illness, 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 5 days

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special lung scan using hyperpolarized xenon gas can enhance understanding of lung diseases. It examines changes in the scan after treatments such as oxygen therapy or blood transfusions. Individuals with chronic lung issues, like interstitial lung disease or chronic blood clots in the lungs, as well as healthy volunteers, may be eligible. The study aims to find better ways to manage lung conditions by analyzing these advanced scans. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in lung disease management.

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 trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that hyperpolarized Xe129 for lung imaging is safe. Studies have found it is well-tolerated by both healthy individuals and those with lung conditions like COPD (chronic obstructive pulmonary disease). The FDA has approved its use for lung MRIs in children aged 12 and older, indicating it is considered safe for regular medical use.

Oxygen therapy is generally safe and commonly used for various conditions. However, some risks exist, such as infection or receiving too much oxygen, which could harm the lungs. Medical settings usually manage these risks well.

Overall, previous research has shown both treatments under study to be safe, although doctors monitor the risks associated with oxygen therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it uses hyperpolarized Xe129 MRI, a cutting-edge imaging technique, to provide detailed pictures of lung function and structure. Unlike traditional imaging methods that primarily focus on the anatomy of the lungs, hyperpolarized Xe129 offers a unique view into how gases move and exchange in the lungs, which is crucial for understanding conditions like chronic thromboembolic pulmonary hypertension (CTEPH) and interstitial lung disease (ILD). This method can potentially lead to more precise diagnoses and better-targeted treatments by revealing functional changes that are not visible with standard imaging techniques.

What evidence suggests that this trial's treatments could be effective for lung disease?

Research has shown that hyperpolarized 129Xe MRI, one of the methods studied in this trial, is a promising tool for assessing lung function. It can detect changes in lung function and structure. Studies have found that this method effectively identifies problems in lung tissue and helps track treatment progress for lung diseases.

Oxygen Administration, another treatment arm in this trial, has evidence suggesting it can improve quality of life and help individuals with interstitial lung disease (ILD) exercise more easily. Oxygen therapy also reduces tiredness and shortness of breath during exercise. These findings support the potential effectiveness of both treatments in managing lung conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Joseph Mammarappallil, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with interstitial lung disease, thromboembolic pulmonary hypertension, or who are healthy volunteers. Participants must be able to give consent and follow the study plan. Smokers or those with recent respiratory illness, certain heart conditions, low oxygen levels, MRI contraindications, inability to hold breath for 10 seconds, pregnancy or lactation are excluded.

Inclusion Criteria

I am over 18 and agree to follow the study rules for my pulmonary embolism.

Exclusion Criteria

I cannot hold my breath for 10 seconds.

Subject deemed unlikely to be able to comply with instructions during imaging

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo interventions such as transfusion, phlebotomy, oxygen administration, or surgical treatment for pulmonary embolism

Up to 5 days

1 visit (in-person)

Follow-up

Participants are monitored for changes in RBC to membrane ratio, RBC chemical shift, and RBC oscillation amplitude

3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized Xe129
• Oxygen Administration

Trial Overview The study tests how three biomarkers from a special type of MRI using hyperpolarized Xenon gas (129Xe) change in response to interventions like oxygen administration. It aims to improve understanding of various lung diseases and their treatment.

How Is the Trial Designed?

Group I: Transfusion and Phlebotomy Patients Active Control 1 Intervention

Individuals receiving treatment for their blood hemoglobin levels or are a healthy volunteer who is planning to donate blood.

Group II: Oxygen Administration Patients Active Control 2 Interventions

Individuals diagnosed with a chronic blood clot in their lungs and are planning on having surgery to remove it (CTEPH), or have an interstitial lung disease (ILD), or have dyspnea, or are a healthy volunteer.

Group III: Acute or Chronic Pulmonary Embolism Patients Active Control 1 Intervention

Individuals recently diagnosed with a blood clot in their lungs.

Who Is Running the Clinical Trial?

Bastiaan Driehuys

Lead Sponsor

Trials

15

Recruited

1,100+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study involving 10 patients with pulmonary hypertension due to heart failure, breathing oxygen-enriched air significantly improved exercise performance, increasing maximum work rate (Wmax) and cycling time during tests.

Patients reported less dyspnea and showed better blood oxygenation and ventilatory efficiency while using oxygen, suggesting that supplemental oxygen could enhance exercise capacity and comfort for those with PH-HFpEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Breathing Oxygen-Enriched Air on Exercise Performance in Patients With Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction: A Randomized, Placebo-Controlled, Crossover Trial. Müller, J., Lichtblau, M., Saxer, S., et al.[2021]

Long-term oxygen therapy is effective in prolonging survival for hypoxemic patients with chronic lung disease, making it a crucial treatment option.

In addition to survival benefits, oxygen therapy can improve various aspects of health, including exercise capacity, sleep quality, and overall pulmonary function, especially in patients experiencing desaturation during activities or sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lung disease: when to prescribe home oxygen. Tarpy, SP., Farber, HW.[2006]

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]

Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with chronic obstructive pulmonary disease (COPD), with no serious adverse events reported.

While 91% of participants experienced mild and transient symptoms such as dizziness and euphoria, these symptoms resolved quickly without the need for clinical intervention, indicating that the procedure is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Driehuys, B., Martinez-Jimenez, S., Cleveland, ZI., et al.[2022]

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]

The recent FDA approval of hyperpolarized 129Xe as an MR contrast agent highlights its growing importance in lung imaging, prompting the need for standardized techniques across research and clinical sites.

The 129Xe MRI Clinical Trials Consortium has established best practices for the entire workflow of 129Xe MRI, including safety monitoring and technical considerations, to ensure effective and safe imaging of lung ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation. Garrison, WJ., Mugler, JP., Mata, JF., et al.[2023]

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 gas is safe and well-tolerated as an inhaled contrast agent for MRI in children, with no serious adverse events reported during the study involving 28 participants aged 6 to 16 years.

While some children experienced mild and temporary changes in oxygen saturation and heart rate after inhalation, these effects were consistent with expected physiological responses and resolved quickly, indicating that 129Xe MRI is feasible for assessing lung function in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Walkup, LL., Thomen, RP., Akinyi, TG., et al.[2022]

The study demonstrated that injecting hyperpolarized xenon-129 (129Xe) into the bloodstream of rats is a safe method that produces a strong signal in the lungs, allowing for effective imaging of pulmonary perfusion and gas exchange.

This technique revealed important insights, such as ventilation-perfusion deficits and temporary impairments in gas exchange due to saline overload, suggesting its potential as a sensitive and non-invasive tool for evaluating lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe. Driehuys, B., Möller, HE., Cleveland, ZI., et al.[2021]

Oxygen therapy significantly improves exercise capacity in patients with chronic respiratory diseases, primarily by reducing dynamic hyperinflation, and is beneficial not only for those with severe hypoxemia but also for mild hypoxemic patients who experience desaturation during exercise.

Both continuous and intermittent oxygen delivery methods are effective in enhancing exercise tolerance and reducing hypoxemia, suggesting that ambulatory oxygen should be prescribed for all patients on long-term oxygen therapy who engage in outdoor activities, as well as for normoxemic patients with severe exertional desaturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits of oxygen on exercise performance in patients with chronic lung diseases]. Nasiłowski, J.[2013]

In a study of 3,046 patients with pulmonary arterial hypertension (PAH), those with severe reduction in lung carbon monoxide diffusing capacity (DLCO) who used supplemental oxygen had a significantly lower risk of all-cause mortality (hazard ratio 0.56) compared to those who did not use oxygen.

There was no observed benefit of supplemental oxygen in patients with no, mild, or moderate DLCO reduction, indicating that oxygen therapy may be particularly beneficial for those with severe lung function impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of supplemental oxygen in patients with pulmonary arterial hypertension in REVEAL. Farber, HW., Badesch, DB., Benza, RL., et al.[2020]

The infusion of oxygen-enriched liquid was effective in correcting severe hypoxemia in 9 patients with SARS and AIDS, showing significant improvements in oxygen levels and vital signs within 20 minutes to 4 hours of treatment.

This novel therapy bypasses damaged alveoli, allowing for increased blood oxygen levels and could be a life-saving option for patients with severe respiratory issues related to infectious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study of infusion of oxygen-enriched liquid to correct severe hypoxemia in infectious diseases: a report of pilot clinical study]. He, Q., Xu, C., Wang, S., et al.[2016]

Citations

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Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary ... Conclusion: The hyperpolarized 129Xe MRI was highly sensitive to regional functional changes in subjects with UIP and may represent a new tool ...

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Hyperpolarized 129Xe MRI and Spectroscopy: Quantitative ... Hyperpolarized xenon 129 (129Xe) MRI uses inhaled 129Xe gas to visualize pulmonary function and microstructure.

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Hyperpolarized 129-Xenon MRI in Fibrosing Interstitial ... This project aims to investigate the potential of non-invasive imaging to identify and monitor the earliest signs and physiological effects of pulmonary ...

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Hyperpolarized Xenon-129 MRI: Narrative Review of ... This indicates that three-dimensional single-breath chemical shift imaging 129XeMRI can effectively characterize lung diseases, monitor treatment responses, and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666675824001589

Direct imaging of pulmonary gas exchange with ... Hyperpolarized 129Xe gas MRI has shown significant promise in detecting and evaluating abnormalities in pulmonary small airways, parenchyma, and ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/214375s000lbl.pdf

XENOVIEW (xenon Xe 129 hyperpolarized), for oral inhalation The safety and effectiveness of XENOVIEW have been established in pediatric patients aged 12 years and older for use with MRI to evaluate lung ventilation.

7. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.220069

Lung Abnormalities Detected with Hyperpolarized 129 Xe ... Hyperpolarized xenon 129 MRI and total lung diffusion capacity for carbon monoxide demonstrate significantly impaired gas transfer in nonhospitalized ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02112929

Regional Lung Imaging Using Hyperpolarized Xenon Gas Hyperpolarized xenon, in the doses given for imaging has been shown to be safe. Conventional MRI has limited use in respiratory disease, because the lung is ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/xenon-xe-129-hyperpolarized-inhalation-route/description/drg-20543669

Xenon xe 129 hyperpolarized (inhalation route) Xenon Xe 129 is a hyperpolarized contrast agent that is inhaled before an MRI to help diagnose problems in the lungs.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3244666/

Safety and Tolerability of Hyperpolarized 129Xe MR ... Chronic Obstructive Pulmonary Disease: Safety and Tolerability of Hyperpolarized 129 Xe MR Imaging in Healthy Volunteers and Patients