MRI with Gadolinium + Ferumoxytol for Brain Conditions

Overseen By Lisa C Muir, MPA:HA, CCRP

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Parenteral iron, Gadolinium

Disqualifiers: Uncal herniation, Pregnancy, Iron overload, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a special MRI using gadolinium (a contrast agent) and ferumoxytol (an iron-based contrast agent) to better diagnose brain and central nervous system issues. The researchers aim to determine how well these imaging agents identify problems like tumors, swelling, or other abnormalities. Participants will receive both agents in different orders to compare results. This trial may suit those with ongoing neurological symptoms, such as frequent headaches or seizures, or those with brain abnormalities found through other tests. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in diagnostic imaging.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have allergies to certain drugs or have received ferumoxytol recently, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that gadolinium-based contrast agents, used in MRI scans, usually do not harm the brain. However, they can sometimes cause side effects like headaches, dizziness, and changes in taste. The FDA is investigating the risk of gadolinium accumulating in the brain with repeated use, but no harmful effects have been found so far.

Ferumoxytol, another MRI contrast agent, has FDA approval for treating iron deficiency anemia, indicating it has been tested for safety in people. However, it can sometimes cause allergic reactions.

Overall, both gadolinium and ferumoxytol are considered safe, but discussing any concerns with a healthcare professional before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using MRI with gadolinium and ferumoxytol for brain conditions because this approach could enhance imaging precision. Unlike standard MRI contrast agents, ferumoxytol is an iron-based compound that can provide clearer, longer-lasting images, which may help in identifying brain abnormalities more accurately. Additionally, by using both gadolinium and ferumoxytol, researchers hope to combine the benefits of two different contrast agents to improve diagnostic capabilities. This dual-contrast method could lead to better diagnosis and treatment planning for patients with complex brain conditions.

What evidence suggests that this MRI technique is effective for diagnosing brain conditions?

This trial will compare gadolinium and ferumoxytol in MRI scans for brain conditions. Studies have shown that both substances enhance MRI clarity, improving the diagnosis of brain and nerve issues. In this trial, participants in Group I will receive gadolinium followed by ferumoxytol, while those in Group II will receive ferumoxytol followed by gadolinium. Gadolinium is commonly used to enhance MRI image detail, especially for the brain. Ferumoxytol, an iron-based agent, also improves MRI results and serves as an option for those allergic to other contrast agents. Both substances highlight certain tissues and blood vessels in the scan, aiding doctors in identifying problems. Although concerns exist about gadolinium accumulating in the brain after multiple uses, no harmful health effects have been proven. These agents aim to provide clearer images, leading to better diagnoses. ^{1 2 5 6 7}

Who Is on the Research Team?

Michael F Regner, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with brain abnormalities (tumors or other issues) who have neurological symptoms like headaches or seizures. They must be over 10 years old, able to undergo MRI without anesthesia, and not pregnant. Women of childbearing age should use contraception. Participants can't join if they have severe brain swelling signs, are pregnant/lactating, have iron overload conditions, recent ferumoxytol use, multiple drug allergies, or certain metal implants.

Inclusion Criteria

I am at least 10 years old.

All subjects, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines

I have experienced neurological symptoms like headaches or seizures.

Exclusion Criteria

Subjects with three or more drug allergies from separate drug classes

I do not have genetic hemochromatosis or it has been ruled out with normal TS and SF tests.

I do not have severe brain symptoms like sudden pupil changes, quick muscle weakness, or fast drops in alertness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gadolinium and ferumoxytol intravenously and undergo MRI over 60 minutes on day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ferumoxytol
• Gadolinium
• Magnetic Resonance Imaging

Trial Overview The study is testing how well two types of MRI contrast agents—gadolinium and ferumoxytol—work in diagnosing central nervous system problems. It aims to improve detection and diagnosis of brain-related health issues by comparing the effectiveness of these imaging techniques.

How Is the Trial Designed?

Group I: Group II (ferumoxytol, gadolinium, MRI) Experimental Treatment 3 Interventions

Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.

Group II: Group I (gadolinium, ferumoxytol, MRI) Experimental Treatment 3 Interventions

Patients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.

Magnetic Resonance Imaging is already approved in United States for the following indications:

Approved in United States as Lumakras (sotorasib) for:

• Non-small cell lung cancer with KRAS G12C mutation

Approved in United States as Vectibix (panitumumab) for:

• Advanced colorectal cancer that is wild-type RAS

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Published Research Related to This Trial

In a study involving 49 pediatric patients and 19 young adults, ferumoxytol was found to be well tolerated as an intravenous MRI contrast agent, with only four mild adverse events reported, all of which were self-resolving.

No significant effects on vital signs, kidney function, or liver enzymes were observed after administration, indicating a favorable safety profile for doses of 5 mg Fe/kg or lower, although further research is needed to assess the risk of anaphylactic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults. Muehe, AM., Feng, D., von Eyben, R., et al.[2018]

Gadolinium-based contrast agents, while commonly used in MRI, raise safety concerns due to risks like nephrogenic systemic fibrosis and tissue deposition, particularly in certain patient populations.

Ferumoxytol presents a promising alternative as a contrast medium for MRI, offering unique properties such as prolonged intravascular signal and delayed uptake by macrophages, which could enhance its clinical applications in abdominal imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pictorial review on abdominal applications of ferumoxytol in MR imaging. Kordbacheh, H., Baliyan, V., Parakh, A., et al.[2020]

In a study of 86 pediatric patients and young adults, ferumoxytol was found to be an effective intravenous MRI contrast agent, with 95.4% of the images rated as at least diagnostic quality by radiologists.

While there was a statistically significant but clinically insignificant drop in blood pressure after ferumoxytol injection, further large-scale studies are needed to determine optimal dosing and safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic safety and efficacy of ferumoxytol as an intravenous contrast agents in pediatric patients and young adults. Ning, P., Zucker, EJ., Wong, P., et al.[2016]

Ferumoxytol-enhanced MRI is as effective as gadolinium-enhanced MRI for detecting intracranial metastatic disease, based on a study of 19 patients with various types of cancer.

The study found no significant differences in the number or size of metastatic lesions detected by either imaging method, suggesting that ferumoxytol could be a safe alternative when gadolinium is contraindicated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI Is Not Inferior to Gadolinium-Enhanced MRI in Detecting Intracranial Metastatic Disease and Metastasis Size. Hamilton, BE., Barajas, R., Nesbit, GM., et al.[2021]

In a study of 49 MRI scans from 70 adults, ferumoxytol was found to provide different enhancement characteristics compared to gadoteridol, particularly in T1-weighted images, suggesting its potential as an alternative MRI contrast agent for patients with renal failure.

Ferumoxytol showed contrast-enhanced hypointensity in 53% of cases, while gadoteridol showed none, indicating that ferumoxytol may have unique diagnostic properties that warrant further investigation across various CNS disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging. Hamilton, BE., Nesbit, GM., Dosa, E., et al.[2021]

Ferumoxytol, an iron oxide nanoparticle approved for treating iron deficiency, is being increasingly used off-label as an MRI contrast agent, especially in pediatric patients, due to its safety profile and lack of long-term tissue retention.

Unlike traditional gadolinium-based contrast agents, ferumoxytol is biodegradable and poses no risk of nephrogenic systemic fibrosis, making it a safer alternative for high-quality vascular and cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art. Adams, LC., Jayapal, P., Ramasamy, SK., et al.[2023]

In a multicenter study involving 3215 patients who received 4240 ferumoxytol injections for MRI, the use of ferumoxytol was well tolerated with no severe or life-threatening adverse events reported.

Only 1.9% of patients experienced adverse reactions related to ferumoxytol, mostly mild, indicating a positive safety profile for its off-label diagnostic use as an alternative to gadolinium-based contrast agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. Nguyen, KL., Yoshida, T., Kathuria-Prakash, N., et al.[2023]

Ferumoxytol shows strong relaxation properties, making it a promising alternative to gadolinium-based contrast agents for magnetic resonance imaging (MRI), with effective relaxivities measured at both 1.5 T and 3.0 T.

The study highlights that while ferumoxytol's relaxation rates are linear in saline and plasma, they exhibit nonlinear behavior in blood, which is crucial for optimizing MRI protocols using this agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relaxivity of Ferumoxytol at 1.5 T and 3.0 T. Knobloch, G., Colgan, T., Wiens, CN., et al.[2020]

Ferumoxytol, an FDA-approved iron supplement, shows promise as a safer alternative to gadolinium-based contrast agents for MRI, particularly in children, as it does not deposit in the brain and can be metabolized.

Studies indicate that ferumoxytol provides significant signal enhancement in MRI, making it a potentially effective option for improving diagnostic accuracy in pediatric imaging compared to traditional gadolinium chelates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. Daldrup-Link, HE., Theruvath, AJ., Rashidi, A., et al.[2022]

Ferumoxytol, an iron oxide nanoparticle, provides enhanced imaging of malignant brain tumors, peaking in contrast enhancement 24 to 28 hours after injection, making it effective for dynamic MRI assessments.

Unlike gadolinium, which leaks from blood vessels early, ferumoxytol remains intravascular during the initial phase, improving the accuracy of tumor perfusion evaluations across various magnetic field strengths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neuwelt, EA., Várallyay, CG., Manninger, S., et al.[2022]

Citations

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Gadolinium Deposition in Neurology Clinical Practice - PMC To date, no evidence links gadolinium deposition with any adverse health outcome. Updated medical society guidelines emphasize the importance of an ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10344828/

Gadolinium contrast agents- challenges and opportunities of a ... Comparing with CAs used in medical modalities, gadolinium contrast has a reduced risk of acute responses than iodine contrast, there is no substitute for MRI ...

3. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/gadolinium-pentetate-meglumine

Gadolinium Pentetate Meglumine - an overview Gadolinium chelates have been used successfully in place of iodinated contrast media for image-guided spine interventions and have become an alternative to ...

4. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-evaluating-risk-brain-deposits-repeated-use-gadolinium-based

FDA evaluating the risk of brain deposits with repeated use ... FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging.

5. emjreviews.com emjreviews.com/flagship-journal/article/the-application-safety-and-recent-developments-of-commonly-used-gadolinium-based-contrast-agents-in-mri-a-scoping-review-j190324/

The Application, Safety, and Recent Developments of ... Gadopentetate dimeglumine was a widely used contrast agent in MRI scans before the suspension, improving accuracy in liver and brain imaging.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11282029/

MRI contrast agents and retention in the brain - PubMed Central Gadolinium currently serves as the basis for MRI contrast agents used clinically. No adverse neurological manifestations have been detected in relation to ...

7. sciencedirect.com sciencedirect.com/topics/nursing-and-health-professions/gadolinium-pentetate-meglumine

Gadolinium Pentetate Meglumine - an overview The most common adverse events of gadobenate dimeglumine were headache (16%), dizziness (4.6%), and taste disturbances (4.6%); the most common adverse reactions ...