Ignite Creation Date:
2024-05-06 @ 10:58 AM
Last Modification Date:
2024-10-26 @ 12:38 PM
Study NCT ID:
NCT03396822
Status:
COMPLETED
Last Update Posted:
2024-02-28
First Post:
2018-01-04
Brief Title:
Meningeal Inflammation on 7T MRI as a Tool for Measuring and Predicting Ocrelizumab Response in Multiple Sclerosis
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Meningeal Inflammation on 7T MRI as a Tool for Measuring and Predicting Ocrelizumab Response in Multiple Sclerosis
Status:
COMPLETED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Multiple Sclerosis MS is an autoimmune disorder of the central nervous system In MS inflammation is known to attack areas of the brain spinal cord and optic nerves resulting in disability Current MRI technology provides an adequate view of the impact of MS on the white matter of the brain which contains many of the connections between neurons Quantification of lesions in the white matter due to MS are a standard part of clinical trials and clinical care in MS However it has long been known that MS not only can affect the white matter but also the gray matter which contains the majority of the nerve cells in the brain and can cause inflammation in the meninges the protective tissue that surrounds the brain and spinal cord Autopsy studies have shown that the inflammation seen in the meninges is driven by a B-cells a subset of white blood cells and that meningeal inflammation may be responsible for damage to the gray matter of the brain
Ocrelizumab is a new treatment for multiple sclerosis This medication works by targeting and destroying circulating B-cells It is thought that this may reduce the level of meningeal inflammation in patients with multiple sclerosis By reducing meningeal inflammation this medication may result in less damage to the gray matter and subsequently less disability in MS patients
In this study the investigators will evaluate the use of a method on 7 tesla 7T MRI to identify inflammation in the meninges as a potential predictor of response to ocrelizumab treatment for multiple sclerosis Further the investigators will evaluate if this MRI technique can be used to monitor the long-term effect of the medication on meningeal inflammation and the development of damage to the gray matter of the brain
Ocrelizumab is a new treatment for multiple sclerosis This medication works by targeting and destroying circulating B-cells It is thought that this may reduce the level of meningeal inflammation in patients with multiple sclerosis By reducing meningeal inflammation this medication may result in less damage to the gray matter and subsequently less disability in MS patients
In this study the investigators will evaluate the use of a method on 7 tesla 7T MRI to identify inflammation in the meninges as a potential predictor of response to ocrelizumab treatment for multiple sclerosis Further the investigators will evaluate if this MRI technique can be used to monitor the long-term effect of the medication on meningeal inflammation and the development of damage to the gray matter of the brain
Detailed Description:
Twenty-two 22 participants will be recruited from the University of Maryland Center for Multiple Sclerosis Treatment and Research Participants will be included if they are aged 18-65 have a diagnosis of relapsing or progressive multiple sclerosis per revised 2010 McDonald Criteria and are planning to begin ocrelizumab therapy for multiple sclerosis as prescribed by their treating physician Participants will be excluded if they are unable to undergo an MRI due to metallic implantsdevices or claustrophobia have a history of allergy to gadolinium contrast or are unable to provide informed consent
All participants will undergo a baselinescreening study visit prior to initiation of ocrelizumab This will include signing of informed consent a clinical interview to collect demographic and clinical data a physical examination to calculate the EDSS score and implementation of the component tests of the Multiple Sclerosis Functional Composite MSFC All participants will then undergo an MRI on a 7T Philips Achieva scanner housed at the Kennedy Krieger Institute Baltimore MD This will be a whole brain MRI including 07mm3 resolution magnetization prepared 2 rapid acquisition gradient echo MP2RAGE and MPFLAIR images acquired both pre- and post-intravenous infusion of gadolinium contrast
MP2RAGE images will be processed to create T1 maps and T1-weighted images All images MPFLAIR included will be co-registered to the pre-contrast MP2RAGE T1 map Subtraction images will be created by subtracting the pre-contrast MPFLAIR scan from post-contrast images Regions of hyperintensity on the subtraction image will be reviewed on anatomical images and marked as regions of leptomeningeal enhancement if they have an amorphous appearance and are present in the leptomeningeal space
Participants who are found to have leptomeningeal enhancement on their baseline scan will be considered as having passed screening and will proceed with further study procedures Those that do not have meningeal enhancement on a baseline scan will not return for a follow up visit
Participants who have passed screening and thus have meningeal enhancement on their baseline scan will then undergo initiation of ocrelizumab per clinical trial or commercial drug protocol as previously planned by their treating neurologists Participants will then return for a follow up visit within 1 month after their 12 month ocrelizumab infusion All of the above study procedures will be repeated on that date
Follow up images for each subject will undergo co-registration to the pre-contrast MP2RAGE T1 map This will allow co-registered review of baseline and 1 year follow up MPFLAIR images side-by-side for review of the presence or absence of enhancing foci noted at baseline on the 1 year follow up scan Subtraction images will also be created utilizing the 1 year pre- and post-contrast MPFLAIR scan for quantification of the number of enhancing foci on the 1 year follow up scan by the same procedures as above A semi-automated region growing painting tool will be used to create masks over areas of contrast enhancement which will be used to quantify enhancing focus volume on the baseline and follow up scan Further subtraction mapping will be utilized to highlight regions of hypointensity present in the cortex on MP2RAGE T1 that were not present on baseline MP2RAGE T1 which would indicate a new cortical lesion at follow up
All participants will undergo a baselinescreening study visit prior to initiation of ocrelizumab This will include signing of informed consent a clinical interview to collect demographic and clinical data a physical examination to calculate the EDSS score and implementation of the component tests of the Multiple Sclerosis Functional Composite MSFC All participants will then undergo an MRI on a 7T Philips Achieva scanner housed at the Kennedy Krieger Institute Baltimore MD This will be a whole brain MRI including 07mm3 resolution magnetization prepared 2 rapid acquisition gradient echo MP2RAGE and MPFLAIR images acquired both pre- and post-intravenous infusion of gadolinium contrast
MP2RAGE images will be processed to create T1 maps and T1-weighted images All images MPFLAIR included will be co-registered to the pre-contrast MP2RAGE T1 map Subtraction images will be created by subtracting the pre-contrast MPFLAIR scan from post-contrast images Regions of hyperintensity on the subtraction image will be reviewed on anatomical images and marked as regions of leptomeningeal enhancement if they have an amorphous appearance and are present in the leptomeningeal space
Participants who are found to have leptomeningeal enhancement on their baseline scan will be considered as having passed screening and will proceed with further study procedures Those that do not have meningeal enhancement on a baseline scan will not return for a follow up visit
Participants who have passed screening and thus have meningeal enhancement on their baseline scan will then undergo initiation of ocrelizumab per clinical trial or commercial drug protocol as previously planned by their treating neurologists Participants will then return for a follow up visit within 1 month after their 12 month ocrelizumab infusion All of the above study procedures will be repeated on that date
Follow up images for each subject will undergo co-registration to the pre-contrast MP2RAGE T1 map This will allow co-registered review of baseline and 1 year follow up MPFLAIR images side-by-side for review of the presence or absence of enhancing foci noted at baseline on the 1 year follow up scan Subtraction images will also be created utilizing the 1 year pre- and post-contrast MPFLAIR scan for quantification of the number of enhancing foci on the 1 year follow up scan by the same procedures as above A semi-automated region growing painting tool will be used to create masks over areas of contrast enhancement which will be used to quantify enhancing focus volume on the baseline and follow up scan Further subtraction mapping will be utilized to highlight regions of hypointensity present in the cortex on MP2RAGE T1 that were not present on baseline MP2RAGE T1 which would indicate a new cortical lesion at follow up
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None