Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation
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|ClinicalTrials.gov Identifier: NCT04230174|
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Using magnetic resonance-PET (MR-PET) imaging with [11C]PBR28, a second-generation 18kDa translocator protein (TSPO) radiotracer, we have previously demonstrated abnormally high TSPO expression, indicative of microglia activation, across different brain tissue compartments of multiple sclerosis (MS) patients1.
In this study, we propose to study the efficacy of ocrelizumab, a humanized monoclonal antibody that has been shown to decrease neuroinflammation in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (MS) patients.
We will test these effects by studying a cohort of 24 MS patients (12 RRMS, 12 progressive MS). Participants will be studied before (within 3 months prior to initiating treatment) and after treatment with ocrelizumab (~12 month follow up), a therapeutic drug that will be part of their standard medical care. We will use [11C]PBR28 to help determine changes in neuroinflammation.
The purpose of this study is to determine the effects of ocrelizumab treatment on neuroinflammation by analyzing the uptake and distribution of [11C]PBR28 in individuals with multiple sclerosis. The specific aims of the current study are:
- To assess whether treatment with ocrelizumab in subjects with either relapsing-remitting MS or progressive MS is associated with decreased [11C]PBR28 binding in the cortex and white matter (lesions and normal appearing white matter), suggesting reduced neuroinflammation.
- To assess whether changes in neuroinflammation under ocrelizumab treatment, as measured by [11C]PBR28 uptake at 12-month follow up relative to baseline, are associated with changes in structural MR metrics of brain tissue damage including white matter lesion load, cortical atrophy, and demyelination in the cortex and in the normal-appearing white matter as measured by magnetization transfer ratio (MTR).
- To explore whether changes in functional and structural imaging metrics under ocrelizumab are associated with changes in clinical outcome measures.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Drug: 11C-PBR28||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||24 multiple sclerosis patients|
|Masking:||None (Open Label)|
|Official Title:||Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation|
|Estimated Study Start Date :||February 2020|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||July 2022|
Experimental: Multiple sclerosis patients
Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy.
This study will evaluate, serially, functional and structural tissue changes in the cortex and WM of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.
- Neuroinflammation Changes under Ocrelizumab Therapy [ Time Frame: 12 months ]To measure changes in 11C-PBR28 uptake in the brain of multiple sclerosis patients under Ocrelizumab therapy
- To assess whether changes in neuroinflammation under Ocrelizumab treatment relate to changes in structural MR metrics of brain tissue damage [ Time Frame: 12 months ]To measure changes in 11C-PBR28 uptake in the brain of multiple sclerosis patients under Ccrelizumab therapy correlate with changes in WM lesion load, cortical atrophy and demyelination in the cortex and in the NAWM as measured by magnetization transfer ratio (MTR)
- To explore whether changes in functional and structural imaging metrics under Ocrelizumab are associated with changes in clinical outcomes measures [ Time Frame: 12 months ]To measure whether changes in 11C-PBR28 uptake or in structural imaging metrics correlate with measures of neurological disability and cognition
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04230174
|Contact: Caterina Mainero, MD, PhDfirstname.lastname@example.org|
|Contact: Ambica Mehndiratta, BScemail@example.com|
|Principal Investigator:||Caterina Mainero, MD, PhD||Massachusetts General Hospital|