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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
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Caterina Mainero, Massachusetts General Hospital

Study Description
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Brief Summary:

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:

  1. 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.
  2. 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).
  3. 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 24 multiple sclerosis patients
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: 11C-PBR28
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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)


Secondary Outcome Measures :
  1. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent
  2. RRMS and/or PMS subtype
  3. EDSS between 0 and 7.0
  4. Express at least one high-affinity (Ala147) allele of the TSPO receptor for PBR28
  5. Initiating Ocrelizumab treatment within the next 3 months

Exclusion Criteria:

  1. Hypersensitivity to trial medications
  2. History of life-threatening reaction to Ocrelizumab
  3. Acute or uncontrolled chronic medical condition
  4. Impaired hearing
  5. Claustrophobia
  6. 300 lbs of greater (weight limit of MRI table)
  7. Pregnancy or breastfeeding
  8. Sensitivity to imaging agents
  9. Contraindications to MRI
  10. Use of benzodiazepines, topiramate, doxycycline, mynocicline
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Caterina Mainero, MD, PhD 617-724-7746 cmainero@mgh.harvard.edu
Contact: Ambica Mehndiratta, BSc 617-724-8823 amehndiratta1@mgh.harvard.edu

Sponsors and Collaborators
Massachusetts General Hospital
Genentech, Inc.
Investigators
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Principal Investigator: Caterina Mainero, MD, PhD Massachusetts General Hospital
More Information
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Responsible Party: Caterina Mainero, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04230174    
Other Study ID Numbers: 2019P002865
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
 Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases