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

Trial Summary

What is the purpose of this trial?

The goal of this NIH-sponsored study is to characterize three biomarkers derived from 129Xe gas exchange MRI and to understand how they change in response to interventions.

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.

What data supports the effectiveness of this treatment for lung disease?

Research shows that oxygen therapy can improve exercise performance and reduce breathlessness in patients with chronic lung diseases and pulmonary hypertension. This suggests that the use of oxygen, as part of the treatment, may help improve lung function and quality of life for patients with lung disease. ^{1 2 3 4 5}

Is hyperpolarized 129Xe MRI safe for humans?

Research shows that hyperpolarized 129Xe MRI is generally safe and well-tolerated in both healthy individuals and those with lung diseases, including children with cystic fibrosis. Studies have evaluated its safety during inhalation and breath-holding, with no significant adverse effects reported. ^{6 7 8 9 10}

How does hyperpolarized 129Xe MRI differ from other treatments for lung disease?

Hyperpolarized 129Xe MRI is unique because it provides detailed images of lung function by assessing both ventilation (airflow) and gas transfer, unlike traditional imaging methods that may not capture these processes as effectively. This technique uses a special form of xenon gas that enhances the MRI signal, allowing for better visualization of lung structure and function, which can be particularly useful in managing lung diseases. ^{8 10 11 12 13}

Research Team

Joseph Mammarappallil, MD

Principal Investigator

Duke University

Eligibility Criteria

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, can follow study rules, and have ILD, CTEPH, or am healthy.

I am over 18, can follow study rules, and need a blood transfusion or have too many red blood cells.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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. Poland pubmed.ncbi.nlm.nih.gov

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

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

Use of supplemental oxygen in patients with pulmonary arterial hypertension in REVEAL. [2020]

3. Switzerland 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. [2021]

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

Chronic lung disease: when to prescribe home oxygen. [2006]

5. China 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]. [2016]

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

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation. [2023]

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

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]