Assessment of Chronic Lung Allograft Dysfunction Using Single-breath & Multi-breath Hyperpolarized Xenon-129 MRI

NCT ID: NCT04941573

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-19
• Study Completion Date: 2025-09-04

Brief Summary

This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129. Once inhaled, this gas can provide information to imagers regarding lung functionality across specific regions of the lungs by assessing the replacement of air during the normal breathing cycle, how much oxygen is in the airspaces, and if the natural spongy tissue structure has been compromised by lung disease. Of the 90 subjects, 70 will be patients who received lung transplantation from the Penn/Temple Lung Transplant Teams and are receiving follow up treatment at HUP or TUH, 10 will be healthy control subjects who participated favorably in our HP 129Xe imaging protocol, and 10 will be patients who have been diagnosed with chronic obstructive pulmonary disease (COPD)-preferentially recruited from the Temple University COPDGene cohort, who have never undergone a lung transplant. 20 of the lung transplant recipient subjects will be patients who have received a recent clinical diagnosis of chronic lung allograft dysfunction (CLAD) prior to enrollment in our study, while the other 50 will have recently undergone their initial transplant surgery at the time of enrollment.

Detailed Description

This study assesses the operating characteristics of HP 129Xe MRI in an effort to evaluate its performance in identifying early signs of CLAD or graft acceptance in 70 total lung transplant recipients, 20 of whom have been recently diagnosed with CLAD, 10 non-transplant COPD subjects, and 10 healthy control patients. These subjects will be recruited from the patients of transplant pulmonologists on the Penn and Temple Lung Transplant Team. Subjects will be recruited regardless of race or gender. Study visits will last 1-2 hours for each subject and will occur at various time points following their operation. The baseline visit will occur at the conclusion of their 3 month post-transplant visit, with study follow-up visits occurring at the conclusion of the 6, 9, 12, 18, and 24 month post-transplant visit. For the convenience of the subjects, most study visits will begin at the conclusion of their follow-up visit with their transplant pulmonologist. If this does not work for the subject, an alternative date will be scheduled and the PFT's/Physical exam results from the most recent visit with their transplant pulmonologist will be used for that study visit. There will be a 45-day imaging window for each post-transplant visit, allowing MR imaging to be performed within 45 days before or after the anticipated imaging date, granting more flexibility for both subjects and researchers to ensure that each imaging session is successfully completed. If patients decide to not participate in this study, their decision will not affect their standing with HUP or their physician. Both healthy control subjects and non-transplant COPD subjects will be imaged twice within approximately one week to ensure imaging metric reproducibility in both cohorts. Diagnosed CLAD subjects will undergo a single imaging session each. The images of the diagnosed CLAD subjects will serve as a necessary reference for predicting the early decline of lung function in pre-CLAD transplant recipients.

Conditions

Lung Transplant Rejection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Post-lung transplant patients not diagnosed with CLAD

This group will have a target enrollment of 50 subjects recruited from the lung transplant patients of pulmonologists from Penn and Temple Lung Transplant Team.

The subjects will undergo hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung at 3, 6, 9, 12, 18, and 24 months following the transplant. Additional pulmonary tests and questionnaires will be performed to assess the lung health status of the patients.

Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Intervention Type: COMBINATION_PRODUCT

Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Post-lung transplant patients diagnosed with CLAD

This group will have a target enrollment of 20 subjects recruited from the lung transplant patients of pulmonologists from Penn and Temple Lung Transplant Team, and whom have been recently diagnosed with CLAD.

The subjects will undergo a single imaging session of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung.

Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Intervention Type: COMBINATION_PRODUCT

Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Non-transplant COPD patients

This group will have a target enrollment of 10 subjects recruited from the pool of advanced stages of COPD visiting patients from Penn and Temple pulmonologists.

The subjects will undergo two imaging sessions of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung within approximately week to ensure imaging metric reproducibility.

Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Intervention Type: COMBINATION_PRODUCT

Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Healthy control subjects

This group will have a target enrollment of 10 subjects recruited from general population and not suffering from any chronic lung diseases.

The subjects will undergo two imaging sessions of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung within approximately week to ensure imaging metric reproducibility.

Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Intervention Type: COMBINATION_PRODUCT

Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Interventions

Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• For transplant recipients: the subject is a lung transplant recipient who is over 18 years of age, underwent lung transplantation at the Hospital of the University of Pennsylvania or Temple University Hospital, and is receiving follow up care from the Penn or Temple Lung Transplantation teams following said transplant. Written informed consent will be obtained and documented after the subject receives oral and written information about the study.
• For diagnosed CLAD patients: the subject is a lung transplant recipient who is over 18 years of age, underwent lung transplantation at the Hospital of the University of Pennsylvania or Temple University Hospital, and has recently received a clinical diagnosis of CLAD. Written informed consent will be obtained and documented after the subject receives oral and written information about the study.
• For non-transplant COPD patients: the subject is over 18 years old, has been diagnosed with chronic obstructive pulmonary disease, and has never received a lung transplant.
• For healthy controls: the subject is over 18 years of age.

Exclusion Criteria

• Patients less than 18 years old
• Patients known to be pregnant - a positive pregnancy test will be used to respectively exclude pregnant patients,
• Any known contraindication to MRI examination
• Anyone with an implanted metal device
• Inability to provide informed consent
• A language, communication, cognitive or behavioral impairment that might interfere with fully informed participation in the study.
• History of uncompensated organ failure (i.e. organ failure that is not stabilized through medical intervention), which will be assessed by the PI.
• Homelessness or other unstable living situation
• Active drug or alcohol dependence
• Claustrophobia
• Subjects weighting more than 300 pounds.
• Subjects with chest size larger than the bore of MRI machine from the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Xemed LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maxim Itkin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

834759

Identifier Type: -

Identifier Source: org_study_id