HP 129Xe MRI for Lung Transplant Rejection

No longer recruiting at 1 trial location

Overseen By Giles Santyr, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Disqualifiers: Pregnancy, Psychiatric disorders, Claustrophobia, 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: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for assessing lung function in individuals who have undergone a double lung transplant. Researchers use a special type of MRI with hyperpolarized 129Xe gas (also known as XENOVIEW or Hyperpolarized Xenon-129) to detect changes in the lungs. The trial targets both stable transplant patients and those with CLAD, a type of chronic lung problem. Candidates may qualify if they have had a double lung transplant, have been stable for over a year, and do not require daily supplemental oxygen. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant advancements in post-transplant care.

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 healthcare provider.

What prior data suggests that hyperpolarized 129Xe MRI is safe for lung transplant recipients?

Research shows that hyperpolarized 129Xenon (129Xe) is generally safe and well-tolerated for lung imaging. Studies have demonstrated that using 129Xe in MRI scans can assess lung function without causing harmful effects. It acts as a contrast agent, enhancing the visibility of lung structures during the scan.

One study found that the FDA approved the process used to prepare 129Xe, further supporting its safety. Although not all studies focused solely on safety, they reported no negative effects from using 129Xe. This suggests that inhaling 129Xe for MRI scans is safe for patients, even those who have had lung transplants.

Overall, 129Xe has been used safely in various imaging studies, providing confidence in its safety for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of hyperpolarized 129Xenon (129Xe) MRI for lung transplant rejection because it offers a unique way to detect and monitor this condition. Unlike traditional methods, which rely on invasive biopsies or imaging techniques with limited sensitivity, 129Xe MRI allows for a non-invasive, detailed visualization of lung function and gas exchange. This technique uses hyperpolarized 129Xe gas that participants inhale, providing clearer and more precise images of lung tissues, potentially identifying rejection earlier and more accurately. This novel approach could lead to quicker interventions and better outcomes for lung transplant recipients.

What evidence suggests that hyperpolarized 129Xe MRI is effective for assessing lung transplant rejection?

Research has shown that hyperpolarized xenon-129 MRI effectively assesses lung function. Studies have found it can identify areas in the lungs that aren't working properly. For lung transplant patients, this technique helps detect changes in lung structure and function. One study found that this method is safe and provides clear images of lung performance. These findings suggest that xenon-129 MRI could be a valuable tool for monitoring lung health after a transplant. Participants in this trial will inhale hyperpolarized 129Xe gas to evaluate its effectiveness in monitoring lung transplant rejection. ^{1 2 3 6 7}

Who Is on the Research Team?

Giles Santyr, PhD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for stable adult lung transplant recipients at UHN Toronto Lung Transplant Program. It includes those diagnosed with CLAD and those without it after a year of follow-up, provided they have an FEV1 over 1.0 L and are double lung transplant recipients. Exclusions apply to pregnant women, individuals unable to travel for MRI scans, or with conditions that prevent MRI use.

Inclusion Criteria

FEV1 > 1.0 L

PFT measurements within 1 month of scan visit

I have received a double lung transplant.

Exclusion Criteria

Baseline oxygen saturation of less than 88%

I cannot travel to get an MRI scan.

I need extra oxygen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants inhale hyperpolarized 129Xe gas and undergo MRI to evaluate lung function and structure

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 129Xenon

Trial Overview The study tests the use of hyperpolarized 129Xe MRI in detecting changes in the lungs of patients who have received transplants. The goal is to see if this imaging method can effectively identify structural and functional changes associated with lung transplant rejection (CLAD).

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 1 Intervention

Participants will inhale hyperpolarized 129Xe gas.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

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 (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 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 (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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04941573

NCT04941573 | Assessment of Chronic Lung Allograft ... This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129.

2. mearis.cms.gov mearis.cms.gov/public/publications/ntap/NTP221017PBF9L

MEARIS™ | Publication | ntap | NTP221017PBF9L - CMS XENOVIEWTM, prepared from the Xenon Xe 129 Gas blend, is a hyperpolarized contrast agent indicated for use with magnetic resonance imaging (MRI) for evaluation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6945824/

Xenon-129 MRI detects ventilation deficits in paediatric ... [7] reported that 62% of their paediatric HSCT cohort had reductions in lung function of >10% in the first 3–9 months post-transplantation.

4. news.med.virginia.edu news.med.virginia.edu/research/scientists-earn-7-4-million-for-research-using-hyperpolarized-xenon-mri-to-study-lung-transplant-rejection-and-abnormal-blood-flow-in-lungs-of-e-cigarette-users/

Scientists Earn $7.4 Million for Lung Research Using ... Michael Shim, MD, were awarded two, five-year NIH R01 grants totaling $7.4 million for research using hyperpolarized xenon-129 MRI to evaluate ...

5. xenoview.net xenoview.net/about-xenoview/efficacy-and-safety/

Efficacy and Safety - Xenoview .net Study results demonstrate well-tolerated, safe, and effective measurement of regional lung ventilation with XENOVIEW.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05550662

HP 129Xe MRI for Evaluation of CLAD in Lung Transplant ... 129Xe-MRI could provide a diagnostic tool that is able to detect CLAD more sensitively and earlier than the current gold standard measurements of spirometry and ...

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

Safety and Tolerability of Hyperpolarized 129Xe MR ... Although these studies reported no adverse events, they were not specifically designed to assess the safety and tolerability of hyperpolarized 129Xe. Xenon, ...