Hp 129Xenon Imaging for Bronchiolitis Obliterans Syndrome

Overseen By Megan Schmitt, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Bleeding disorders, Claustrophobia, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 3

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The research is being conducted to develop new imaging methods that are sufficiently sensitive to allow for early diagnosis of BOS, a chronic allograft rejection affecting 50-60% of lung transplanted recipients who survive 5 years after transplant. Although lung transplantation has evolved into an effective therapeutic option for a large number of pediatric patients with end-stage pulmonary disease, long-term survival after lung transplantation is far worse than after the transplantation of other solid organs. This research may improve patient outcomes through earlier diagnosis of changes leading to BOS by obtaining image guided research biopsies of transplanted lung. Biopsies may be used for future research of ex vivo biomarkers of BOS and in the development of treatments through future clinical trials.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Hp 129Xenon, Hyperpolarized 129-Xenon, Xe-129 for Bronchiolitis Obliterans Syndrome?

Research shows that Hyperpolarized 129 Xenon MRI is a promising tool for assessing lung function, as it can evaluate ventilation and gas transfer, which are crucial for understanding lung diseases. This imaging technique has been used to study various lung conditions, suggesting its potential usefulness in managing lung-related issues. ^{1 2 3 4 5}

Is Hp 129Xenon imaging safe for humans?

Research indicates that hyperpolarized 129Xenon (HP 129Xe) MRI is generally considered safe for use in humans, including children, as a contrast agent for lung imaging. It has been used in studies for various lung conditions, and safety considerations have been a focus in its development. ^{1 2 3 4 6}

How does hyperpolarized 129 Xenon imaging differ from other treatments for bronchiolitis obliterans syndrome?

Hyperpolarized 129 Xenon imaging is unique because it is a non-invasive imaging technique that allows doctors to see how well air moves in and out of the lungs and how gases are exchanged in the lung tissue. This is different from other treatments that might focus on medication or surgery, as it provides detailed images to help understand lung function and guide treatment decisions. ^{1 2 4 5 7}

Research Team

Jason Woods, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for people who had a lung transplant within the last decade or are being evaluated for one. They must be able to hold their breath up to 16 seconds. It's not suitable for those with bleeding disorders, claustrophobia, recent respiratory infections, pregnant individuals, or anyone who can't undergo MRI scans.

Inclusion Criteria

I have had a lung transplant in the last 10 years or am being considered for one.

You can hold your breath for about 16 seconds.

Exclusion Criteria

Standard MRI exclusion criteria

I have a bleeding disorder.

You feel very uncomfortable in small spaces or cannot stay still for medical scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Biopsy

Participants undergo 129Xe MRI and image-guided bronchial biopsies to detect early BOS and understand disease progression

6 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and biopsy procedures

6 months

1 visit (in-person)

Long-term Follow-up

Participants are followed up to 12 months post-transplant to capture MRI images for clinician assessment

12 months

Treatment Details

Interventions

• Hp 129Xenon

Trial Overview The study is testing Hp129 Xenon as a new imaging method aimed at early detection of Bronchiolitis Obliterans Syndrome (BOS), which affects many lung transplant recipients over time. The goal is to use these images to guide biopsies and help develop future treatments.

Participant Groups

Group I: Hp 129Xenon Experimental Treatment 1 Intervention

Participants will inhale up to 4 doses of Hp129Xenon; each dose will be no more than 1 liter.

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

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]

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]

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]

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 continuous flow-type hyperpolarizing (CF-HP) system allows for effective lung imaging using hyperpolarized (129)Xe MRI at very low concentrations of xenon, minimizing the anesthetic effects and reducing xenon consumption.

Using a 70% xenon gas mixture resulted in better signal-to-noise ratios for both gas and dissolved-phase images compared to a 3% mixture, although the apparent diffusion coefficient (ADC) was higher with the 3% mixture, indicating a complex relationship between concentration and imaging quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. Wakayama, T., Kitamoto, M., Ueyama, T., et al.[2015]

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 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]

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

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

3. Ireland pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. [2015]

6. 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]

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

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