Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI
Primary Purpose
Stroke, Intracranial Atherosclerosis
Status
Enrolling by invitation
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ferumoxytol Injectable Product
Sponsored by
About this trial
This is an interventional diagnostic trial for Stroke
Eligibility Criteria
80 patients will be enrolled in this prospective cross-sectional study of 2 cohorts:(A) Intracranial atherosclerosis & (B) Intracranial aneurysms
Inclusion Criteria:
(A) cohort: 60 intracranial atherosclerosis (stenosis less than 25%)
- recent ischemic stroke (less than or equal to 14 days)
(B) cohort: 20 intracranial aneurysms patients participants:
- 10 asymptomatic
- 10 with recent intracranial aneurysm(s) rupture (less than or equal to 7 days).
Exclusion Criteria:
- Less than 18 years old
- Documented history of atrial fibrillation (for intracranial atherosclerosis cohort).
- Carotid stenosis greater than 70% (for intracranial atherosclerosis cohort).
- Pregnant women
- Contrast allergy
- Acute or chronic kidney disease with glomerular filtration rate<30 ml/min/1.73m2
- Intravenous iron sensitivity
- Serum ferritin and transferrin saturation above age-adjusted upper limit of normal. If serum ferritin is above normal, but transferrin saturation is normal, the patient is not excluded.
- Pacemaker or other MRI contraindications
Sites / Locations
- Yale University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
80 patients with intracranial atherosclerosis
Outcomes
Primary Outcome Measures
Vessel Wall Enhancement with Gadolinium compared to Vessel Wall Enhancement with Ferumoxytol in intracranial atherosclerosis (ICAS) group.
Both patient groups will have a high-resolution vessel wall enhancement-gadolinium MRI at baseline with a delayed high-resolution vessel wall enhancement-Ferumoxytol MRI. Prevalence will be analyzed between the different participants in each group.
Hypothesis: Participants with intracranial atherosclerosis will have a high prevalence of vessel wall enhancement.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03084523
Brief Title
Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI
Official Title
Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
April 26, 2017 (Actual)
Primary Completion Date
November 27, 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Intracranial atherosclerosis (ICAS) accounts for 10 to 40%, depending on ethnicity, of the 700,000 ischemic strokes in the United States every year. The annual rate of recurrent stroke in patients with optimally treated ICAS remains more than twice the average of other stroke etiologies (12.5% vs. 5). A robust literature has established that vessel wall magnetic resonance imaging (vwMRI) of extracranial carotid vessel wall enhancement (VWE) can predict stroke, independent of stenosis. VWE has been reported in symptomatic ICAS, but the role of local and systemic inflammation is unknown. Inflammatory biomarkers are elevated in symptomatic extracranial atherosclerosis, but the association with vwMRI findings in ICAS has not yet been explored. VWE is typically demonstrated by the uptake of gadolinium MRI contrast into the aneurysm wall or atherosclerotic plaque. A novel MRI contrast agent, ferumoxytol, allows multi-contrast weighting on T1w and T2w images and provides important insight into the role of local vessel wall inflammation by accumulating in macrophages on delayed T2* sequences. To identify effective prevention and treatment strategies for cerebrovascular disease, we need to critically evaluate vwMRI techniques, determine VWE prevalence, and explore the link between VWE and inflammation.
Detailed Description
Intracranial atherosclerosis accounts for 10 to 40%, depending on ethnicity, of the 700,000 ischemic strokes in the United States every year.The annual rate of recurrent stroke in patients with optimally treated Intracranial atherosclerosis remains more than twice the average of other stroke etiologies (12.5% vs. 5%).A robust literature has established that vessel wall MRI of extracranial carotid vessel wall enhancement can predict stroke, independent of stenosis. Vessel wall enhancement has been reported in symptomatic intracranial atherosclerosis. Vessel wall enhancement is typically demonstrated by the uptake of gadolinium MRI contrast into the atherosclerotic plaque. A novel MRI contrast agent, ferumoxytol, allows multicontrast weighting on T1w and T2w images and provides important insight into the role of local vessel wall inflammation by accumulating in macrophages on delayed T2* sequences.
To identify effective prevention and treatment strategies for cerebrovascular disease, the investigator(s) need to critically evaluate vessel wall MRI techniques, determine vessel wall enhancement prevalence, and explore the link between vessel wall enhancement and inflammation. The investigator(s) hypothesize that vessel wall enhancement is reliable, associated with symptomatic Intracranial atherosclerosis. In order to answer our hypotheses, the investigator(s) propose a pilot study on 80 participants. The investigator(s) will opportunistically enroll participants who receive standard of care vessel wall MRI with gadolinium contrast or perform a baseline vessel wall MRI with gadolinium if needed. Intracranial atherosclerosis participants will have a total of 2-3 study vessel wall MRIs. Study MRI #1 will be performed with gadolinium, if a standard of care MRI has not already been performed. Study MRI #2 will be performed 72-78 hours post- using ferumoxytol contrast infusion. Study MRI #3 is a follow-up vessel wall MRI with gadolinium in 1 year.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Intracranial Atherosclerosis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
80 patients with intracranial atherosclerosis
Intervention Type
Drug
Intervention Name(s)
Ferumoxytol Injectable Product
Other Intervention Name(s)
Feraheme
Intervention Description
Patients will be administered a single dose of ferumoxytol as an MRI contrast
Primary Outcome Measure Information:
Title
Vessel Wall Enhancement with Gadolinium compared to Vessel Wall Enhancement with Ferumoxytol in intracranial atherosclerosis (ICAS) group.
Description
Both patient groups will have a high-resolution vessel wall enhancement-gadolinium MRI at baseline with a delayed high-resolution vessel wall enhancement-Ferumoxytol MRI. Prevalence will be analyzed between the different participants in each group.
Hypothesis: Participants with intracranial atherosclerosis will have a high prevalence of vessel wall enhancement.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
80 patients will be enrolled in this prospective cross-sectional study of Intracranial atherosclerosis.
Inclusion Criteria:
intracranial atherosclerosis (stenosis ≥50%)
recent ischemic stroke (less than or equal to 14 days)
Exclusion Criteria:
Less than 18 years old
Documented history of atrial fibrillation
Carotid stenosis greater than 70%
Pregnant women
Contrast allergy
Acute or chronic kidney disease with glomerular filtration rate<30 ml/min/1.73m2
Intravenous iron sensitivity
Serum ferritin and transferrin saturation above age-adjusted upper limit of normal. If serum ferritin is above normal, but transferrin saturation is normal, the patient is not excluded.
Pacemaker or other MRI contraindications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam de Havenon, MD
Organizational Affiliation
Yale School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI
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