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

Trial Summary

What is the purpose of this trial?

Temporal lobe epilepsy (TLE) is a common type of epilepsy and one of the most likely to not be controlled by medication. For patients who do not respond to medication, surgery can result in a cure of seizures. Given the fact that around 50% of patients who undergo surgery are seizure free at 10 years there is a need to improve the understanding of what factors best predict surgical outcomes in order to improve our ability to select candidates for surgery. The demonstration of abnormalities in the temporal lobe on MRI is one of the best predictors of seizure free surgical outcomes. Recent studies suggest that changes in specific subregions of the hippocampus could be the strongest predictors of surgical success, however the small size of these regions, (millimeters) make them very difficult to study with standard clinical MRI. Recently new MRI methods have been developed at Wayne State University to image hippocampal blood vessels using ferumoxytol infusion. Feraheme (ferumoxytol) is a drug that is approved in the United States for the treatment of iron deficiency anemia and is currently being studied as an MRI contrast agent in 8 active clinical trials in the United States as well as a Parkinson's Disease study in Canada.

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 drug Ferumoxytol, Feraheme, in enhancing MRI imaging for epilepsy?

Research shows that a similar MRI contrast agent, which includes superparamagnetic iron oxide, improves the visibility of seizure-related brain areas in mouse models of epilepsy. This suggests that Ferumoxytol, which also contains iron oxide, might help in better identifying epileptic regions in humans. ^{1 2 3 4 5}

Is ferumoxytol safe for use in 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 study. Mild to moderate reactions occurred in a small percentage of cases, similar to minor reactions seen with other iron infusions. ^{6 7 8 9 10}

How does the enhanced MRI imaging treatment for epilepsy differ from other treatments?

This treatment uses a special MRI contrast agent that responds to electric-field changes in the brain during seizures, improving the visibility of seizure foci in patients with drug-resistant epilepsy. Unlike standard MRI, this approach enhances the detection of epileptic lesions that are not easily seen, potentially increasing the success of surgical interventions. ^{1 2 3 11 12}

Research Team

Donald Gross, MD

Principal Investigator

University of Alberta

Eligibility Criteria

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

I weigh more than 127.5 kg.

Inability to provide informed consent

I am a woman who can have children and my pregnancy test is positive.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

References

1. England 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. [2021]

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

MR imaging of epilepsy: state of the art at 1.5 T and potential of 3 T. [2006]

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

Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages. [2022]

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

Diagnostic value of MRI in the presurgical evaluation of patients with epilepsy: influence of field strength and sequence selection: a systematic review and meta-analysis from the E-PILEPSY Consortium. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Construction of Pepstatin A-Conjugated ultrasmall SPIONs for targeted positive MR imaging of epilepsy-overexpressed P-glycoprotein. [2021]

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

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. [2023]

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

What Does the Boxed Warning Tell Us? Safe Practice of Using Ferumoxytol as an MRI Contrast Agent. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Incidental ferumoxytol artifacts in clinical brain MR imaging. [2018]

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

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Hemodynamic safety and efficacy of ferumoxytol as an intravenous contrast agents in pediatric patients and young adults. [2016]

11. Germany pubmed.ncbi.nlm.nih.gov

Ultra-fast low-angle rapid acquisition and relaxation enhancement (UFLARE) in patients with epilepsy. [2019]

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

Efficacy of gadolinium administration in magnetic resonance imaging screening of patients with complex partial seizures and results of a normal neurologic examination. [2019]