Intracranial AtherosclerosisPhase 4NCT05515874
Predicting Stroke Risk in ICAD With Novel MRI
A Phase 4 study testing Feraheme in people with Intracranial Atherosclerosis, run by Northwestern University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Intracranial Atherosclerosis
- What is being tested?
- Feraheme
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 30 Jun 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than 18 - 85 years
- All symptomatic patients referred to the Stroke Neurology, Cerebrovascular Surgery, or Interventional Neuroradiology inpatient/outpatient clinical services at Northwestern University or the University of Chicago with diagnosis of intracranial atherosclerosis.
- CTA/MRA/DSA imaging findings confirm the presence of moderate to severe stenosis >50% of ≥ 1 segment of the supra-clinoid ICA, A1-A2 ACA, M1-M2 MCA, distal vertebral-basilar artery, P1-P2 PCA and complete cervical or intracranial carotid occlusions utilizing the SAMMPRIS stenosis criteria (3) Symptomatic patients defined as an association between the intracranial stenosis and perfusion/thromboembolic ischemia related symptoms of the corresponding vascular territory, based on either neurological exam (TIAs/stroke) and/or acute/subacute infarcts documented on MR-DWI within 7 days of presentation.
Who cannot join
- Standard contraindications to MRI: claustrophobia, metallic implants, pacemaker, compromised kidney function (GFR < 40 ml/min), history of reaction to MRI contrast agent, history of allergic reactions to ferumoxytol or other IV iron products,
- elderly patients > 85 years
- multiple or serious medical conditions, or history of multiple drug allergies Other confounders of neuro-functional exams, i.e. Alzheimer's Disease or dementia.
- Severe >70% cervical carotid or vertebral artery proximal stenosis, or tandem intracranial stenosis
- VULNERABLE POPULATIONS
- N/A
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Predicting Stroke Risk in Intracranial Atherosclerotic Disease With Novel High Resolution, Functional and Molecular MRI Techniques
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.
Read the detailed description
The long-term goal of this work is to reduce the incident of stroke by identifying the most vulnerable patients using MRI scans. Currently roughly 1 of every 8 patient who have had an initial stroke from intracranial atherosclerosis disease (ICAD) will suffer a second stroke within a year. Patients who are likely to fail medical management have loss of cerebrovascular reserve, poor collateral arterial blood supply, and/or inflammatory plaque that is vulnerable to rupture from active macrophage infiltration. Investigator's goal is to identify vulnerable patients to inform the selection for new medical management protocols or intervention with intracranial stenting or stent-less angioplasty. Investigators will develop a suite of novel MRI scans and evaluate them in the intended patient population, comparing to reference standard CO2 Challenge CVR, HMPAO SPECT, and to perform direct intracranial plaque molecular imaging for active macrophages.
ICAD is one of the most common causes of stroke worldwide with a high risk of recurrent stroke. ICAD patients with severe stenosis (70 to 99%) are at particularly high risk for recurrent stroke in the vascular territory of the stenosis (~12 to 20% within 12 months), despite aggressive treatment with aspirin, clopidogrel (Plavix), management of risk factors (hypertension, smoking etc.), and lifestyle modification. The use of new, preventative treatments including angioplasty/stenting or new anti-platelet/anti-inflammatory medications would benefit the most vulnerable patients that may be able to be identified with investigator's MR imaging protocol prior to the failure of medical management. Investigator's novel MR imaging biomarkers will improve the risk stratification for ICAD related stroke and recurrent stroke in this vulnerable, high risk population.
The Specific Aims of this study are:
Specific Aim 1: To develop and validate an MRI scan protocol for quantification of cerebrovascular reserve that does not require externally administered physiologic stressors.
Specific Aim 2: To develop and validate an MRI tissue perfusion protocol that can quantify the blood supplied through critical collateral arterial pathways.
Specific Aim 3: To correlate dynamic contrast enhancement (Ktrans plaque permeability) and Fe- ferumoxytol uptake, as MRI biomarkers of inflammation (macrophage infiltration) in unstable ICAD plaques.
Upon successful completion of this proposal Investigators will have developed three biomarkers of key risk factors for ICAD related stroke that will alter the management of patients in favor of earlier stroke prevention.
- Conditions
- Intracranial Atherosclerosis
- Being tested
- Feraheme
- Keywords
- STROKE, PLAQUE, STENOSIS
- Medical subject headings
- Intracranial Arteriosclerosis, Stroke, Plaque, Amyloid, Constriction, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerahemeDrug
Also called ferumoxytol, iron
Ferumoxytol contains iron and is used for the treatment of anemia, so it may affect any iron supplementation prescribed by a physician. Iron is metabolized in the liver, so impaired liver function could interfere with the metabolism of ferumoxytol.
Patients will receive up to a total maximum ferumoxytol dose of 4 mg/kg (71.6 µmol Fe/kg) of body weight, diluted in 200 mL of 0.9% normal saline, at a rate of 10 ml/minute for 20 minutes, The injection rate and maximum dosage are well within the safety thresholds regarding the FDA recommendation of ferumoxytol use.
| Study group | Role | What they receive |
|---|---|---|
| Feumoxytol infusion and MRI Brain | Experimental | 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. Receives: Drug: Feraheme |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome
1.Primary
CG-OEF based CVR measured as tissue oxygen extraction a peak Systolic vs mid-diastolic cardiac phase correlates with reference standard perfusion changes measures in response to hypercapnia challenge (CO2 inhalation).
OEFCVR=(OEF_Systolic-OEF_Diastolic)/OEF_Systolic x 100%
Primary Outcome Measure: Local change in CVR (as a percentage) in areas of the brain affected by atherosclerosis.
CVR = (CBF2- CBF1)/CBF1 X 100%,
where CBF is tissue perfusion, measured before (CBF1) and after (CBF2) inhalation of CO2.
Measured: one year - We are not using clinical endpoints, it is a developmental and pilot feasibility study of novel MRI applications to assess MR OEF/CVR, using quantitative MR PWI as marker of disease severity]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2022
- Study start1 Sep 2020
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Why it stopped: No participants were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracranial AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Chicago
- Responsible party
- Sponsor
- Investigators
- Sameer A Ansari, MD, PhD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05515874
- Sponsor's protocol ID
- STU00212754
- Status last verified
- Mar 2026
- First submitted
- 21 Dec 2021
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Stroke Risk in Intracranial Atherosclerotic Disease With Novel High Resolution, Functional and Molecular MRI Techniques
- ClinicalTrials.gov ID
- NCT05515874
- Acronym / sponsor ID
- STU00212754
- Conditions
- Intracranial Atherosclerosis
- Keywords
- STROKE, PLAQUE, STENOSIS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- University of Chicago
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 25 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The long-term goal of this work is to reduce the incident of stroke by identifying the most vulnerable patients using MRI scans. Currently roughly 1 of every 8 patient who have had an initial stroke from intracranial atherosclerosis disease (ICAD) will suffer a second stroke within a year. Patients who are likely to fail medical management have loss of cerebrovascular reserve, poor collateral arterial blood supply, and/or inflammatory plaque that is vulnerable to rupture from active macrophage infiltration. Investigator's goal is to identify vulnerable patients to inform the selection for new medical management protocols or intervention with intracranial stenting or stent-less angioplasty. Investigators will develop a suite of novel MRI scans and evaluate them in the intended patient population, comparing to reference standard CO2 Challenge CVR, HMPAO SPECT, and to perform direct intracranial plaque molecular imaging for active macrophages.
ICAD is one of the most common causes of stroke worldwide with a high risk of recurrent stroke. ICAD patients with severe stenosis (70 to 99%) are at particularly high risk for recurrent stroke in the vascular territory of the stenosis (~12 to 20% within 12 months), despite aggressive treatment with aspirin, clopidogrel (Plavix), management of risk factors (hypertension, smoking etc.), and lifestyle modification. The use of new, preventative treatments including angioplasty/stenting or new anti-platelet/anti-inflammatory medications would benefit the most vulnerable patients that may be able to be identified with investigator's MR imaging protocol prior to the failure of medical management. Investigator's novel MR imaging biomarkers will improve the risk stratification for ICAD related stroke and recurrent stroke in this vulnerable, high risk population.
The Specific Aims of this study are:
Specific Aim 1: To develop and validate an MRI scan protocol for quantification of cerebrovascular reserve that does not require externally administered physiologic stressors.
Specific Aim 2: To develop and validate an MRI tissue perfusion protocol that can quantify the blood supplied through critical collateral arterial pathways.
Specific Aim 3: To correlate dynamic contrast enhancement (Ktrans plaque permeability) and Fe- ferumoxytol uptake, as MRI biomarkers of inflammation (macrophage infiltration) in unstable ICAD plaques.
Upon successful completion of this proposal Investigators will have developed three biomarkers of key risk factors for ICAD related stroke that will alter the management of patients in favor of earlier stroke prevention.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Feumoxytol infusion and MRI Brain | Experimental | Drug: FerahemeAn 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age greater than 18 - 85 years
- All symptomatic patients referred to the Stroke Neurology, Cerebrovascular Surgery, or Interventional Neuroradiology inpatient/outpatient clinical services at Northwestern University or the University of Chicago with diagnosis of intracranial atherosclerosis.
- CTA/MRA/DSA imaging findings confirm the presence of moderate to severe stenosis >50% of ≥ 1 segment of the supra-clinoid ICA, A1-A2 ACA, M1-M2 MCA, distal vertebral-basilar artery, P1-P2 PCA and complete cervical or intracranial carotid occlusions utilizing the SAMMPRIS stenosis criteria (3) Symptomatic patients defined as an association between the intracranial stenosis and perfusion/thromboembolic ischemia related symptoms of the corresponding vascular territory, based on either neurological exam (TIAs/stroke) and/or acute/subacute infarcts documented on MR-DWI within 7 days of presentation.
Key exclusion criteria (6 listed)
- Standard contraindications to MRI: claustrophobia, metallic implants, pacemaker, compromised kidney function (GFR < 40 ml/min), history of reaction to MRI contrast agent, history of allergic reactions to ferumoxytol or other IV iron products,
- elderly patients > 85 years
- multiple or serious medical conditions, or history of multiple drug allergies Other confounders of neuro-functional exams, i.e. Alzheimer's Disease or dementia.
- Severe >70% cervical carotid or vertebral artery proximal stenosis, or tandem intracranial stenosis
- VULNERABLE POPULATIONS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FerahemeAlso: ferumoxytol, ironFerumoxytol contains iron and is used for the treatment of anemia, so it may affect any iron supplementation prescribed by a physician. Iron is metabolized in the liver, so impaired liver function could interfere with the metabolism of ferumoxytol. Patients will receive up to a total maximum ferumoxytol dose of 4 mg/kg (71.6 µmol Fe/kg) of body weight, diluted in 200 mL of 0.9% normal saline, at a rate of 10 ml/minute for 20 minutes, The injection rate and maximum dosage are well within the safety thresholds regarding the FDA recommendation of ferumoxytol use. | Drug | Feumoxytol infusion and MRI Brain |
Primary outcome
Primary Outcome
Time frame: one year - We are not using clinical endpoints, it is a developmental and pilot feasibility study of novel MRI applications to assess MR OEF/CVR, using quantitative MR PWI as marker of disease severity]
1.Primary CG-OEF based CVR measured as tissue oxygen extraction a peak Systolic vs mid-diastolic cardiac phase correlates with reference standard perfusion changes measures in response to hypercapnia challenge (CO2 inhalation). OEFCVR=(OEF_Systolic-OEF_Diastolic)/OEF_Systolic x 100% Primary Outcome Measure: Local change in CVR (as a percentage) in areas of the brain affected by atherosclerosis. CVR = (CBF2- CBF1)/CBF1 X 100%, where CBF is tissue perfusion, measured before (CBF1) and after (CBF2) inhalation of CO2.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Intracranial Atherosclerosis
Not yet recruiting
EDAS Revascularization for Symptomatic Intracranial Atherosclerotic Steno-occlusive Disease
Intracranial Atherosclerosis, Intracranial Arterial Stenosis
RecruitingObservational study
BASIS Technique for Endovascular Therapy of Acute Large Vessel Occlusion Strokes Due to Intracranial Atherosclerotic Disease
Acute Ischemic Stroke, ICAS - Intracranial Atherosclerosis
Not yet recruiting
INtensive liPid-lowering Therapy for Acute High-risk IntracRanial or Extracranial atheroSclerosis -II (INSPIRES-2)
Ischemic Stroke or High-risk TIA (ABCD² ≥ 4)
Not yet recruitingPhase 4
RESCUE: PCSK9 Inhibitors for Carotid Vulnerable Plaque Remodeling
Atherosclerosis Cerebral, Carotid Plaque
RecruitingObservational study
High-resolution Magnetic Resonance Imaging of Intracranial Atherosclerotic Plaques in Ischemic Stroke
Stroke, Intracranial Atherosclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sameer A Ansari, MD, PhD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Feraheme in people with Intracranial Atherosclerosis, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome (time frame: one year - We are not using clinical endpoints, it is a developmental and pilot feasibility study of novel MRI applications to assess MR OEF/CVR, using quantitative MR PWI as marker of disease severity]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.