Enhanced MRI Imaging for Epilepsy

Overseen By Sandy Arcand

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Disqualifiers: Non-English, Pregnancy, Breastfeeding, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve surgery outcomes for people with temporal lobe epilepsy (TLE) by using new MRI imaging techniques. It targets individuals with medication-resistant TLE, particularly those with hippocampal changes visible on an MRI. The study uses Ferumoxytol (also known as Feraheme), a drug originally used for anemia, to enhance MRI brain images. Participants should have TLE with hippocampal sclerosis visible on an MRI. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 this MRI method is safe for epilepsy patients?

Research has shown that ferumoxytol, the treatment under study, has been used in other medical studies and is generally safe. In a large study with 8,666 patients, only 0.2% experienced serious side effects. The most common side effects were mild, such as diarrhea, headache, and nausea. However, a small risk of serious allergic reactions exists.

Ferumoxytol is already approved in the U.S. for treating iron deficiency anemia, which enhances its safety profile. While it is usually well-tolerated, discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Ferumoxytol for enhanced MRI imaging in epilepsy because it offers a unique approach to visualizing brain activity. Unlike standard imaging techniques, Ferumoxytol acts as a superparamagnetic iron oxide nanoparticle, providing clearer and more detailed images of brain structures. This could lead to better detection and understanding of epileptic foci, potentially improving diagnosis and treatment planning. The prospect of obtaining more precise images with Ferumoxytol could revolutionize how doctors approach and manage epilepsy compared to current imaging methods.

What evidence suggests that this MRI method is effective for predicting surgical outcomes in temporal lobe epilepsy?

Studies have shown that using ferumoxytol as an MRI contrast agent can enhance the imaging of small brain areas, such as the hippocampus. This is crucial because changes in these regions might predict the success of epilepsy surgery. In this trial, participants will receive ferumoxytol, which alters the magnetic properties of tissues, allowing doctors to see blood vessels more clearly in MRI scans. Research indicates that this method is generally safe and does not cause serious side effects. By providing clearer images, it could help identify the best candidates for epilepsy surgery and potentially lead to better outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Donald Gross, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with temporal lobe epilepsy (TLE), a common type of epilepsy that often doesn't respond to medication. Participants should be interested in undergoing MRI scans using ferumoxytol, an iron supplement being tested as a contrast agent.

Inclusion Criteria

I am 18-64 with temporal lobe epilepsy and MRI shows my hippocampus is scarred.

Exclusion Criteria

Inability to provide informed consent

Women who are actively breast feeding

I am not allergic to Feraheme or any IV iron products.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ferumoxytol infusion and undergo MRI imaging to assess hippocampal microvasculature

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse events post-MRI and data quality is assessed

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ferumoxytol

Trial Overview The study tests advanced MRI techniques using ferumoxytol to better visualize blood vessels in the hippocampus—a brain area critical for TLE. The goal is to improve how we predict who will benefit from surgery by studying these small regions more clearly.

How Is the Trial Designed?

Group I: Ferumoxytol (Feraheme) Experimental Treatment 1 Intervention

Each participant and control will receive Ferumoxytol (Feraheme) 4 mg/kg diluted with 60ml normal saline, administered at 150-200ml/Hr by a registered nurse using a MRI compatible IV infusion pump

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

A new MRI contrast agent that can cross the blood-brain barrier significantly improves the visualization of lesions in patients with drug-resistant focal epilepsy, potentially increasing the effectiveness of surgical treatment.

In mouse models, this contrast agent responds to electric-field changes during seizures, enhancing MRI signals and helping to identify seizure foci that are otherwise difficult to detect, which could lead to better diagnosis and management of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An electric-field-responsive paramagnetic contrast agent enhances the visualization of epileptic foci in mouse models of drug-resistant epilepsy. Wang, C., Sun, W., Zhang, J., et al.[2021]

A new epilepsy-specific MRI protocol was developed based on a study of 2,740 patients, which includes essential sequences like FLAIR and T(2)-weighted images to reliably detect small epileptogenic lesions.

This protocol, featuring specific slice thickness and orientations, aims to improve early identification of patients who may benefit from epilepsy surgery, making it practical for use outside specialized centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages. Wellmer, J., Quesada, CM., Rothe, L., et al.[2022]

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 is a promising alternative to standard gadolinium-based contrast agents for MRI, especially in patients with impaired kidney function, due to its unique properties like prolonged blood pool phase and delayed intracellular uptake.

Clinical studies indicate that ferumoxytol is generally safe and effective, with very few cases of anaphylactoid reactions, making it a viable option for imaging various organs and the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Toth, GB., Varallyay, CG., Horvath, A., et al.[2022]

In a study of 671 MR imaging procedures using ferumoxytol in 331 patients, no serious or life-threatening adverse events were reported, indicating a strong safety profile for this contrast agent.

The overall rate of mild adverse events was 10.6%, with common issues including hypertension and nausea, suggesting that while some patients may experience side effects, serious complications are rare when proper precautions are taken.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Does the Boxed Warning Tell Us? Safe Practice of Using Ferumoxytol as an MRI Contrast Agent. Varallyay, CG., Toth, GB., Fu, R., et al.[2023]

Ferumoxytol, an intravenous treatment for iron deficiency anemia, can cause significant imaging artifacts in brain MRIs performed within 3 days of administration, affecting the diagnostic quality of the scans.

Recognizing these artifacts, such as susceptibility effects on various MRI sequences and altered vascular signals, is crucial for clinicians to avoid misinterpretations and unnecessary follow-up examinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidental ferumoxytol artifacts in clinical brain MR imaging. Bowser, BA., Campeau, NG., Carr, CM., et al.[2018]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06483061

Enhanced MRI Imaging in Healthy Participants and ... Recently high-resolution vascular imaging of the hippocampus using ferumoxytol as an MRI contrast agent has been reported by researchers at Wayne State ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5505659/

Current and Potential Imaging Applications of Ferumoxytol for ... Ferumoxytol for MR imaging. Initially, ferumoxytol was developed as an MRI contrast agent due to its effectiveness in shortening T1 and T2 relaxation times.

3. withpower.com withpower.com/trial/phase-2-epilepsy-8-2024-ab12f

Enhanced MRI Imaging for Epilepsy Ferumoxytol, used as an MRI contrast agent, has been shown to be generally safe in humans, with no severe or life-threatening adverse events reported in a large ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06483061/enhanced-mri-imaging-in-healthy-participants-and-participants-with-epilepsy

Enhanced MRI Imaging in Healthy Participants and ... New MRI methods have been developed at Wayne State University to image hippocampal blood vessels using ferumoxytol infusion.

5. clinicaltrials.eu clinicaltrials.eu/inn/ferumoxytol/

Ferumoxytol – Application in Therapy and Current Clinical ... As an Imaging Agent: When used in MRI, the iron particles in ferumoxytol affect the magnetic properties of tissues, allowing for enhanced visualization of blood ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/022180s025lbl.pdf

Feraheme. - accessdata.fda.gov Risk Summary. Limited available data with ferumoxytol use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/76/NCT00659776/Prot_SAP_000.pdf

NCT00659776 MR, Histologic and EM Imaging Of ... To assess side effects/safety of ferumoxytol when given during MRI. ... An independent Data Monitoring Committee met to review the clinical safety data for all.

8. go.drugbank.com go.drugbank.com/drugs/DB06215

Ferumoxytol: Uses, Interactions, Mechanism of Action Hypersensitivity. The FDA has Feraheme (ferumoxytol) may cause serious hypersensitivity reactions, including anaphylaxis and/or anaphylactoid reactions.

9. feraheme.com feraheme.com/wp-content/uploads/2020/07/Radiologist-Letter.pdf

Dear Radiologist Adverse Reactions The most common adverse reactions (≥ 2%) are diarrhea, headache, nausea, dizziness, hypotension, constipation, and peripheral edema. Please ...