Predicting Stroke Risk in ICAD With Novel MRI

Intracranial Atherosclerosis Clinical Trial

Official title:

Predicting Stroke Risk in Intracranial Atherosclerotic Disease With Novel High Resolution, Functional and Molecular MRI Techniques

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05515874
• Other study ID #: STU00212754
• Status: Recruiting
• Phase: Phase 4
• Start date: August 16, 2021
• Est. completion date: March 30, 2026

Study information

• Verified date: November 2023
• Source: Northwestern University
• Contact: Sameer A Ansari, MD, PhD
• Phone: 215-740-0191
• Email: s-ansari[@]northwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 30, 2026
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Atherosclerosis
• Intracranial Arteriosclerosis
• Intracranial Atherosclerosis

Intervention

Drug:
• Feraheme
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.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]