Novel MRI for Predicting Stroke Risk in Brain Artery Disease

Overseen By Timothy J Carroll, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwestern University

Disqualifiers: Claustrophobia, Metallic implants, Dementia, 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: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new type of MRI to better predict stroke risk in individuals with certain brain artery diseases. The MRI examines blood flow and oxygen use in the brain, potentially aiding doctors in understanding and planning treatments for conditions like aneurysms and intracranial atherosclerosis, where brain arteries narrow. Participants will undergo various MRI procedures, including Neurovascular Imaging, to determine which provides the best insights. This trial suits those who have experienced symptoms like transient ischemic attacks or strokes related to intracranial atherosclerosis and have imaging tests showing significant artery narrowing. As a Phase 4 trial, this research aims to understand how the already FDA-approved MRI benefits more 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 is the safety track record for these treatments?

Research has shown that ferumoxytol infusion, used in one part of this trial, is generally safe but carries some risks. Studies have found that allergic reactions, though uncommon, can occur. Low blood pressure has also been reported. Most mild side effects occur within 48 hours of the infusion and are not life-threatening.

For the MRI with the Tc-99m-HMPAO tracer, research indicates that this tracer is often used in medical imaging to assess blood flow in the brain. It is generally safe, and side effects are rare. The tracer mimics natural substances in the body, aiding doctors in observing brain function.

Both treatments have been studied in other settings, demonstrating a good safety record. However, discussing any personal health concerns with a doctor before joining a trial is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this trial?

Researchers are excited about these imaging techniques because they offer new ways to assess stroke risk in brain artery disease. Unlike standard imaging methods, the MRI with Gadavist uses a pulse oximeter to sync with the heartbeat, aiming to gauge oxygen use in the brain, a potential stroke predictor. The MRI with the Tc-99m-HMPAO tracer provides detailed blood flow insights using a unique tracer that mimics natural body processes. Meanwhile, the ferumoxytol infusion MRI provides a different angle by using a non-gadavist contrast to possibly highlight inflammation or other risk factors. These innovative approaches could lead to more precise stroke risk assessments, paving the way for better prevention strategies.

What evidence suggests that this trial's treatments could be effective for predicting stroke risk in brain artery disease?

Research shows that MRI scans with ferumoxytol, which participants in this trial may receive, effectively highlight brain areas affected by blood vessel problems. Ferumoxytol, an iron-based substance, clarifies MRI images by revealing changes in the brain's blood supply. Studies have found that MRIs enhanced with ferumoxytol are safe and provide clear images, aiding doctors in predicting future stroke risk. The trial also tests MRI with the Tc-99m-HMPAO tracer, which visualizes blood flow in the brain to identify potential issues. Each technique offers unique insights into cerebral blood movement and assists in planning treatments for conditions like stroke. These imaging methods help doctors understand and manage stroke risk in patients with intracranial atherosclerotic disease (ICAD). ^{3 6 7 8 9}

Who Is on the Research Team?

Sameer Ansari, MD, PhD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with intracranial atherosclerosis confirmed by imaging, showing moderate to severe stenosis. Participants must have symptoms linked to this condition and be referred by specific clinical services at Northwestern University or the University of Chicago.

Inclusion Criteria

I have severe narrowing in certain brain arteries confirmed by imaging and have had symptoms or a stroke related to this.

I have been diagnosed with intracranial atherosclerosis and am seeing a specialist at Northwestern University or the University of Chicago.

Exclusion Criteria

I am over 85 years old.

I do not have serious medical conditions or a history of drug allergies, and I am free from Alzheimer's or dementia.

I don't have claustrophobia, metallic implants, a pacemaker, severe kidney issues, or allergies to MRI contrast or IV iron.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI Evaluation

Participants undergo various MRI scans to evaluate cerebrovascular reserve, tissue perfusion, and inflammation in ICAD plaques.

1-2 weeks

Multiple visits for MRI scans

Treatment Evaluation

Evaluation of different treatment options and outcomes based on MRI findings to stratify treatment routes.

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after MRI evaluations and treatment stratification.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Feraheme
• Neurovascular Imaging
• Standard of Care MRI Imaging
• Treatment Evaluation

Trial Overview The study tests Feraheme's effectiveness in predicting stroke risk in patients with ICAD using MRI. It evaluates brain lesions and treatment outcomes to determine which standard care options are most effective based on mortality and morbidity rates.

How Is the Trial Designed?

Group I: Arm 3 - Feumoxytol infusion and MRI Brain Experimental Treatment 1 Intervention

An intravenous ferumoxytol infusion (before the patient leaves Northwestern or University of Chicago after stroke care or at another visit) and an MRI exam 72 hours later. This MRI examination will last approximately 30 minutes and will not involve gadavist. All arm 3 procedures will be performed either at Northwestern or University of Chicago.

Group II: Arm 1 - MRI Brain with Gadavist Active Control 1 Intervention

A research MRI exam that uses the signal from a finger pulse oximeter to synchronize the MRI scan to the subjects heart beat will be acquired. The Gadavist contrast injection will be used during this MRI examination to provide images of cerebral blood flow which will serve as reference standard to identify regions of the brain compromised by cerebral vascular disease. The experimental MRI scan in this case is intended to measure the utilization of oxygen by the brain which is believed to be a predictor of future stroke. All arm 1 procedures will be performed either at Northwestern or University of Chicago.

Group III: Arm 2 - MRI Brain with Tc-99m-HMPAO tracer Active Control 1 Intervention

This type of MRI shows the flow of blood in different areas of the brain and will be performed at University of Chicago. This is done with a tracer called Tc-99m-HMPAO, injected through a vein in the arm. HMPAO is Technetium-99m hexamethyl propylenamine oxime and used clinically to assess blood supply in the brain. This MRI will be performed one hour after the injection of this tracer at University of Chicago and will last up to one hour. A tracer is a specially designed drug that is bound to a radioactive material. Tracers are designed to act like natural products in the body allowing imaging to look at how the body is working. Tracers are designed to look at very specific organ functions and, in this case, brain.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study of 26 patients with moyamoya disease, MR angiography accurately identified 82% of arteries, while MR imaging identified 70%, indicating that both imaging techniques are effective for assessing this condition.

MR imaging showed higher sensitivity (92%) compared to MR angiography (73%) for diagnosing moyamoya disease, suggesting that using both methods together provides the most comprehensive evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moyamoya disease: comparison of assessment with MR angiography and MR imaging versus conventional angiography. Yamada, I., Suzuki, S., Matsushima, Y.[2016]

In a study of 154 patients with carotid plaques, carotid MRI revealed that symptomatic patients had significantly higher rates of intraplaque hemorrhage (IPH), fibrous cap rupture (FCR), and gadolinium enhancement (GE) compared to asymptomatic patients, indicating these features are associated with plaque vulnerability.

The study found that IPH was consistently higher in symptomatic patients regardless of the time since their neurological event, while FCR differences were significant only within the first 15 days after the event, suggesting that carotid MRI can be a valuable tool in assessing plaque risk and guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution magnetic resonance imaging of carotid atherosclerosis identifies vulnerable carotid plaques. Millon, A., Mathevet, JL., Boussel, L., et al.[2015]

Magnetic resonance imaging (MRI) techniques, including diffusion weighted imaging and perfusion imaging, are being integrated into stroke clinical trials to enhance patient selection based on specific ischemic pathophysiology.

These imaging methods serve as direct biomarkers to assess the effectiveness of treatments for ischemic stroke, potentially leading to more targeted and effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of diffusion and perfusion magnetic resonance imaging as a tool in acute stroke clinical trials. Warach, S.[2020]

Neuroimaging, especially MRI, is crucial for assessing individual stroke patients, as it can help tailor treatments based on the specific risk of damage and potential for recovery.

Current MRI techniques are being utilized in both preclinical research and clinical settings to better characterize strokes, which may lead to improved treatment decisions and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of magnetic resonance imaging to predict outcome after stroke: a review of experimental and clinical evidence. Farr, TD., Wegener, S.[2022]

Novel MRI techniques, such as diffusion-weighted and perfusion-weighted imaging, are enhancing the noninvasive assessment of brain function and are already improving the clinical management of acute stroke patients.

Other advanced MRI methods, like spectroscopic imaging and diffusion tensor imaging, show promise for future research in understanding stroke recovery, although they have not yet been widely adopted in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications. Neumann-Haefelin, T., Moseley, ME., Albers, GW.[2007]

In a study of 81 patients with posterior circulation large artery occlusion, susceptibility-weighted MRI successfully identified thrombi in 33.3% of symptomatic patients, indicating its potential as a diagnostic tool.

The presence of blooming artifacts on MRI was significantly more common in patients with cardioembolic strokes (60%) compared to those with other causes, suggesting that this imaging technique can help differentiate the underlying mechanisms of stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial Posterior Circulation Large Artery Thrombi Visualized Using Susceptibility-Weighted MRI. Wang, N., Hu, Q., Wang, Q., et al.[2018]

MRI is not only crucial for diagnosing ischemic stroke but also serves as a prognostic tool that can predict clinical outcomes based on the severity and location of the ischemic damage, as well as cerebral blood flow dynamics.

The development of prognostic algorithms that utilize MRI data can help clinicians tailor treatments for patients, optimizing the risk-benefit ratio for therapies in both acute and chronic stages of ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of MRI as a prognostic tool in ischemic stroke. Arsava, EM.[2012]

In a study of 2403 ischemic stroke events among 2269 patients, MRI findings did not significantly alter the incidence estimates of strokes when compared to a strictly clinical definition of stroke.

Both definitions of stroke (clinical case definition and physician's opinion including MRI) resulted in similar incidence rates, indicating that MRI does not substantially change the classification of stroke events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of Magnetic Resonance Imaging (MRI) on ischemic stroke detection and incidence: minimal impact within a population-based study. Kleindorfer, D., Khoury, J., Alwell, K., et al.[2018]

The study successfully demonstrated that MRI with targeted contrast agents can effectively detect the neuroinflammatory biomarker ICAM-1 after a stroke, highlighting its potential for diagnosis and treatment monitoring.

Among the tested agents, the ICAM-1-targeted micron-sized iron oxide particles (MPIO) were found to be the most effective for in vivo MRI detection of cerebrovascular inflammation, despite both agents showing similar binding efficacy in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI of ICAM-1 upregulation after stroke: the importance of choosing the appropriate target-specific particulate contrast agent. Deddens, LH., van Tilborg, GA., van der Toorn, A., et al.[2022]

In a study of 136 hospital-admitted stroke patients, 62% were able to undergo MRI, indicating that MRI can be a viable first-line imaging option for acute stroke cases.

However, medical instability was the primary reason for not performing MRI, and hypoxia occurred in 18% of patients during the scan, highlighting the need for careful monitoring by experienced clinicians during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance brain imaging in patients with acute stroke: feasibility and patient related difficulties. Hand, PJ., Wardlaw, JM., Rowat, AM., et al.[2018]

In a study involving 148,489 patients over 10 years, gadoteric acid (Dotarem®) was found to be a safe MRI contrast agent, with only 0.3% of patients experiencing adverse events, primarily mild symptoms like nausea and vomiting.

The diagnostic effectiveness was high, with 99.8% of examinations yielding useful results and excellent or good image quality in 97.7% of cases, indicating that gadoteric acid is effective for routine MRI procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients. Braun, J., Busse, R., Darmon-Kern, E., et al.[2020]

Magnetic resonance angiography (MRA) is increasingly used for diagnosing carotid bifurcation atherosclerotic disease and is effective in screening and diagnostic settings.

MRA is also valuable for detecting intracranial aneurysms, characterizing arteriovenous malformations, evaluating intracranial atherosclerotic disease, and noninvasively diagnosing arterial dissection, while magnetic resonance venography (MRV) helps confirm cerebral venous thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR angiography of the head and neck. Patel, MR., Edelman, RR.[2004]

This study analyzed 29 patients with various intracranial vasculopathies using multicontrast vessel wall MRI, demonstrating that combining T1- and T2-weighted imaging significantly improves the differentiation of intracranial atherosclerotic disease (ICAD) from other conditions, increasing sensitivity from 90.1% to 96.3%.

ICAD lesions were found to have distinct characteristics, such as a higher likelihood of eccentric wall involvement (90.1%) and T2 hyperintensity (79%), compared to reversible cerebral vasoconstriction syndrome and vasculitis, indicating that these imaging features can help accurately identify the type of vasculopathy present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicontrast high-resolution vessel wall magnetic resonance imaging and its value in differentiating intracranial vasculopathic processes. Mossa-Basha, M., Hwang, WD., De Havenon, A., et al.[2022]

Contrast-enhanced high-resolution MRI is a feasible method for evaluating changes in symptomatic middle cerebral artery (MCA) stenotic plaques over time, as demonstrated in a study of 7 patients followed from 1 month to 7 months after stroke onset.

The study found that in 4 out of 7 patients, the signal intensity of plaques decreased over time, indicating potential stability, while 2 patients experienced ischemic strokes, suggesting that monitoring plaque changes could be crucial for predicting stroke recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced High-Resolution MRI for Evaluating Time Course Changes in Middle Cerebral Artery Plaques. Abe, A., Sekine, T., Sakamoto, Y., et al.[2018]

In a study of 40 patients with acute pontine infarction, high-resolution MRI revealed that those with undetected basilar artery plaques had significantly worse functional outcomes compared to those without plaques, including higher rates of neurological deterioration and unfavorable outcomes.

The presence of relevant basilar artery plaques was identified as a strong independent predictor of poor functional recovery, even when standard MRA results appeared normal, highlighting the importance of using HR-MRI for better patient assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implications of Basilar Artery Plaques in the Pontine Infarction with Normal Basilar Angiogram: A High-Resolution Magnetic Resonance Imaging Study. Cho, HJ., Kim, KH., Kim, EJ., et al.[2019]

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