Predicting Stroke Risk in ICAD With Novel MRI

NCT05515874 | Completed Phase 4 FDA Drug

• 1 other identifier: STU00212754
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Intracranial Atherosclerosis

Keywords

STROKE; PLAQUE; STENOSIS

Outcome Measures

Primary Outcomes (1)

• 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.

  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]

Study Arms (3)

Arm 1 - MRI Brain with Gadavist

NO 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.

Arm 2 - MRI Brain with Tc-99m-HMPAO tracer

NO 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.

Arm 3 - 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.

Drug: Feraheme

Interventions

Feraheme DRUG

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.

Also known as: ferumoxytol, iron

Arm 3 - Feumoxytol infusion and MRI Brain

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• University of Chicago: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Intracranial Arteriosclerosis; Stroke; Plaque, Amyloid; Constriction, Pathologic

Interventions

Ferrosoferric Oxide; Iron

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Metals, Heavy; Elements; Transition Elements; Metals

Study Officials

• Sameer A Ansari, MD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Radiology

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: August 25, 2022
• Study Start: September 1, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)