Imaging Techniques for Chronic Rejection

Overseen By Sean Fain, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sean Fain

Disqualifiers: Cardiac disease, Pregnancy, Oxygen dependence, others

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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This studies purpose is to confirm the efficacy and efficiency of using OE-MRI and MRI with hyperpolarized gas techniques and Iodinated contrast CT scan, this will enhance understanding of CLAD pathophysiology. Moreover, this project is foundational to performing additional studies to establish if novel MRI imaging can serve as an objective confirmatory diagnostic tool for CLAD in post-transplant patients.

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 the treatment 129Xe MRI scans and Oxygen enhanced magnetic resonance imaging (OE-MRI) Scan for chronic rejection?

Research shows that oxygen-enhanced MRI can help detect lung function issues in patients with lung transplants, and similar techniques have been used to assess lung conditions like bronchiolitis obliterans syndrome. These imaging methods can provide valuable information about lung health and help monitor transplant patients. ^{1 2 3 4 5}

Is it safe to use MRI imaging techniques like 129Xe MRI and OE-MRI in humans?

MRI imaging techniques, including those using gadolinium-based contrast agents, are generally considered safe, with low rates of adverse reactions like hypersensitivity. However, there is limited data on specific risks like nephrogenic systemic fibrosis (a rare condition affecting the skin and organs) in patients with severe kidney issues. ^{6 7 8 9 10}

How does the treatment using 129Xe MRI scans and Oxygen enhanced MRI differ from other treatments for chronic rejection?

The treatment using 129Xe MRI scans and Oxygen enhanced MRI is unique because it provides detailed imaging of lung function and ventilation without the need for invasive procedures. Unlike traditional methods, it uses hyperpolarized xenon gas and oxygen to enhance MRI images, allowing for a non-invasive assessment of lung health and function, which is particularly useful for detecting changes related to chronic rejection. ^{3 11 12 13 14}

Research Team

Sean Fain, Ph.D

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for English-speaking adults aged 18-80 who have had a bilateral lung transplant at least 6 months ago. They must be non-smokers with stable lung function tests and no current lung infections or rejection. Participants need to have normal chest X-rays and be able to consent.

Inclusion Criteria

I am between 18 and 80 years old.

I speak English.

My lung function tests are stable and above 90% of my best recorded values.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Testing

Subjects undergo MRI with hyperpolarized gas techniques, Iodinated contrast CT scan, and pulmonary function tests

1 session

1 visit (in-person)

Follow-up

Participants are monitored for changes in lung function and imaging results

3 months

Treatment Details

Interventions

• 129Xe MRI scans
• Oxygen enhanced magnetic resonance imaging (OE-MRI) Scan

Trial Overview The study is testing the effectiveness of advanced MRI techniques (OE-MRI, hyperpolarized gas MRI) and contrast-enhanced CT scans in understanding Chronic Lung Allograft Dysfunction (CLAD) in patients who've undergone lung transplants.

Participant Groups

Group I: Post Lung Transplant with normal functioning Experimental Treatment 4 Interventions

Subjects who have had a lung transplant and now have normal lung function

Group II: Post Lung Transplant with Chronic Lung Allograft Dysfunction (CLAD) Experimental Treatment 4 Interventions

Subjects who have had a lung transplant that now have CLAD

Group III: Healthy Normal Subjects Active Control 4 Interventions

Healthy subjects, with no lung diagnosis, who are non-smokers.

Who Is Running the Clinical Trial?

Sean Fain

Lead Sponsor

Trials

1

Recruited

100+

Findings from Research

In a study of 728 patients and 25 volunteers, regadenoson stress cardiac magnetic resonance (CMR) was found to be safe, with no serious adverse events like death or myocardial infarction reported.

The most common side effects were mild, including dyspnoea (30%), chest discomfort (27%), and headache (15%), indicating that while some patients experienced discomfort, the overall tolerability of regadenoson CMR is high.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of regadenoson CMR. Nguyen, KL., Bandettini, WP., Shanbhag, S., et al.[2021]

In a study of 72,839 patients undergoing gadolinium-enhanced cardiac magnetic resonance imaging, the incidence of acute adverse events (AAEs) was low at 0.36%, with severe AAEs occurring in only 0.033% of cases.

AAE rates were influenced by factors such as the type of gadolinium-based contrast agent used, the presence of pharmacological stress during imaging, and the specific indications for the imaging, with higher rates observed during stress imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients. Uhlig, J., Lücke, C., Vliegenthart, R., et al.[2021]

Over a 10-year period, the FDA received 1568 reports of adverse events related to magnetic resonance (MR) systems, with 1548 reports analyzed, highlighting the importance of monitoring safety in MR imaging.

The most common serious injuries reported were thermal events, accounting for 59% of cases, followed by mechanical events (11%), projectile events (9%), and acoustic events (6%), indicating specific risks associated with MR environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-related FDA adverse event reports: A 10-yr review. Delfino, JG., Krainak, DM., Flesher, SA., et al.[2020]

Gadoxetic acid, a gadolinium-based contrast agent, showed a low incidence of hypersensitivity reactions (0.3%) in 14,850 administrations, with no reported deaths, indicating a favorable safety profile.

The risk of nephrogenic systemic fibrosis (NSF) in patients with severe kidney impairment remains uncertain, with an upper bound estimate of 2.8% based on limited data, suggesting more research is needed to fully understand this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis. Schieda, N., van der Pol, CB., Walker, D., et al.[2020]

Ferumoxytol-enhanced cardiac MRI can be safely performed without anesthesia in neonates and young infants, showing a low need for additional imaging (only 4.8% of cases required further diagnostics).

The 4D flow MRI technique was found to be significantly better than MR angiography for assessing various cardiac structures, indicating its potential as a superior imaging method for complex congenital heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia. Lai, LM., Cheng, JY., Alley, MT., et al.[2018]

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]

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]

References

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

Chronic Lung Allograft Dysfunction: Oxygen-enhanced T1-Mapping MR Imaging of the Lung. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation. [2021]

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

Review of oxygen-enhanced lung mri: Pulse sequences for image acquisition and T1 measurement. [2023]

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

Utility of cardiac magnetic resonance imaging for the diagnosis of heart transplant rejection. [2019]

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

Noninvasive assessment of early kidney allograft dysfunction by blood oxygen level-dependent magnetic resonance imaging. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of regadenoson CMR. [2021]

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

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients. [2021]

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

MRI-related FDA adverse event reports: A 10-yr review. [2020]

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

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis. [2020]

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

Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia. [2018]

11. England pubmed.ncbi.nlm.nih.gov

T1 based oxygen-enhanced MRI in tumours; a scoping review of current research. [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. England pubmed.ncbi.nlm.nih.gov

Oxygen-enhanced 3D radial ultrashort echo time magnetic resonance imaging in the healthy human lung. [2021]

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

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