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

Trial Summary

What is the purpose of this trial?

The cerebral and spinal vasculature possesses several unique properties: it is composed of relatively small vessels, it has a highly connected network architecture, and, due to the confined space around the brain, disruptions in flow (rupture, shunting, or blockage) can cause a clinical impact quickly. These features apply across various pathological conditions that alter the distribution of blood through the cerebral vasculature, such as aneurysm, intracranial atherosclerotic disease (ICAD) and arteriovenous malformation (AVM) as well as others. Neurovascular disease is a leading cause of mortality due to stroke in the United States and encompasses a broad range of pathologies including but not limited to cerebral arteriovenous malformation, intracranial atherosclerotic disease, intracranial aneurysms and other neurovascular abnormalities. Novel modalities for assessing disease states in patients with these pathologic conditions are constantly being developed and the understanding of risk factors, disease progression, and effective therapy is rapidly evolving. Neurovascular imaging is at the forefront of this progress. The identification of new predictive biomarkers regarding the risk of rupture, progression, or recurrence will improve prognosis and treatment planning. In this study, there will be evaluation of the various types of brain lesions and different treatment options that have been used by the treating physicians and, grade outcome based on the standard of care MRI imaging. This can help the Investigators stratify the treatment routes, that are better than the other by assessing the mortality and morbidity rates. Investigators are evaluating intracranial lesions and their treatment outcomes can help analyze which standard of care treatment is better than the others at a setting like Northwestern.

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 treatment Feraheme in predicting stroke risk in brain artery disease?

Research shows that MRI, especially with advanced imaging techniques, is a valuable tool in predicting stroke outcomes and guiding treatment decisions. This suggests that using MRI with Feraheme, a contrast agent, could help in assessing stroke risk and tailoring individual treatment plans. ^{1 2 3 4 5}

Is the novel MRI for predicting stroke risk safe for humans?

MRI is generally considered safe for humans, and a large study involving 148,489 patients found that MRI with intravenous contrast had a low rate of adverse events (unwanted effects). ^{6 7 8 9 10}

How is Neurovascular Imaging different from other treatments for brain artery disease?

Neurovascular Imaging, using advanced MRI techniques, is unique because it provides a noninvasive and rapid way to assess brain function and blood flow, helping to predict stroke risk more accurately than traditional methods. Unlike other treatments, it uses diffusion-weighted and perfusion-weighted imaging to offer detailed insights into brain artery conditions without the need for invasive procedures. ^{11 12 13 14 15}

Research Team

Sameer Ansari, MD, PhD

Principal Investigator

Northwestern University

Eligibility Criteria

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.

I am between 18 and 85 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

MRI of ICAM-1 upregulation after stroke: the importance of choosing the appropriate target-specific particulate contrast agent. [2022]

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

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

4. Japan pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced High-Resolution MRI for Evaluating Time Course Changes in Middle Cerebral Artery Plaques. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

High-resolution magnetic resonance imaging of carotid atherosclerosis identifies vulnerable carotid plaques. [2015]

7. England 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. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Magnetic resonance brain imaging in patients with acute stroke: feasibility and patient related difficulties. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients. [2020]

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

MR angiography of the head and neck. [2004]

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

New magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications. [2007]

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

Intracranial Posterior Circulation Large Artery Thrombi Visualized Using Susceptibility-Weighted MRI. [2018]

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

Multicontrast high-resolution vessel wall magnetic resonance imaging and its value in differentiating intracranial vasculopathic processes. [2022]

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

Moyamoya disease: comparison of assessment with MR angiography and MR imaging versus conventional angiography. [2016]

15. United States 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. [2019]