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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new imaging techniques, such as special MRI scans, to better understand and diagnose chronic lung rejection in lung transplant patients. The study aims to determine if these scans can reliably confirm lung issues post-transplant. Participants fall into three groups: those with normal lung function after a transplant, those with lung problems after a transplant, and healthy non-smokers without lung issues. Suitable candidates include non-smokers who had a lung transplant at least six months ago or healthy non-smokers without lung problems. As a Phase 1, Phase 2 trial, this research focuses on understanding how the imaging works in people and measuring its effectiveness in a smaller group, offering participants a chance to contribute to groundbreaking diagnostic advancements.

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 prior data suggests that these imaging techniques are safe for post-transplant patients?

Research shows that both 129Xe MRI scans and oxygen-enhanced MRI scans are under study for their safety and usefulness in detecting lung problems. Studies have found that 129Xe MRI scans can identify lung issues earlier than traditional methods. Although specific safety data for 129Xe MRI scans is limited, previous studies suggest they are safe for patients with lung transplants.

For oxygen-enhanced MRI, earlier research suggests it can help predict problems related to lung transplants. While detailed safety information isn't widely available, using oxygen in MRI scans is generally considered non-invasive and low-risk.

Since this trial is in the early stages, it primarily focuses on assessing safety and effectiveness, meaning safety data is still being collected. Participants should consider this when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these imaging techniques for chronic rejection because they offer a new way to understand lung function after transplant. Unlike traditional biopsies or CT scans, 129Xe MRI and Oxygen Enhanced MRI (OE-MRI) provide non-invasive, detailed images of how air and blood flow through the lungs. This could help detect chronic lung allograft dysfunction (CLAD) earlier and more accurately. By improving how we monitor lung health, these techniques have the potential to guide better treatment decisions and improve outcomes for transplant patients.

What evidence suggests that these imaging techniques are effective for chronic rejection?

Research has shown that 129Xe MRI scans, one of the imaging techniques studied in this trial, can detect early signs of chronic lung allograft dysfunction (CLAD), a serious issue for lung transplant patients. Studies have found that these scans can predict the onset of CLAD, which affects up to 80% of lung transplant recipients within five years. The oxygen-enhanced MRI (OE-MRI), another technique under investigation, also shows promise in detecting CLAD-related problems. It can identify issues with lung grafts, possibly before other symptoms appear. This trial examines both MRI methods for their ability to provide early warnings, potentially leading to better long-term outcomes for patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Sean Fain, Ph.D

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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.

I am willing and able to give my consent for treatment.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

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

NCT04941573 | Assessment of Chronic Lung Allograft ... 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 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2950133424000661

Hyperpolarized 129 Xe MRI and spectroscopy of gas ... Chronic lung allograft dysfunction (CLAD) is the leading cause of long-term mortality in lung transplant recipients and is of paramount concern for clinicians.

3. reporter.nih.gov reporter.nih.gov/project-details/11109637

Predicting the onset of chronic rejection in lung transplant ... Summary Up to 80% of lung transplant recipients who survive beyond five years will develop chronic lung allograft dysfunction (CLAD), a heterogenous, ...

4. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.230636

Using Functional Lung MRI to Predict Chronic ... Recorded outcomes were CLAD and survival at 5.6 years. Of the 24 ... 129Xe MRI Clinical Trials Consortium. https://www.129xectc.org ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05550662

HP 129Xe MRI for Evaluation of CLAD in Lung Transplant ... Lung transplantation is an effective treatment for end-stage lung disease. However, median survival post-LTx is 6 years. This is primarily due to chronic lung ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522250618

Novel Magnetic Resonance Imaging for Assessment of ... This pilot study shows that UTE and HP 129 Xe MRI are feasible in patients with bronchial stenosis related to lung transplantation and may provide structural ...

7. go.drugbank.com go.drugbank.com/conditions/DBCOND0066453

Lung Transplant Rejection (DBCOND0066453) HP 129Xe MRI for Evaluation of CLAD in Lung Transplant ... Safety of Endobronchial Mesenchymal Stromal Cells in the Treatment of Chronic Lung Allograft ...