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NCT Number: NCT04230174

Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation

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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Nervous System Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Hypersensitivity to trial medications
  • History of life-threatening reaction to Ocrelizumab
  • Acute or uncontrolled chronic medical condition
  • Impaired hearing
  • Claustrophobia
  • 300 lbs of greater (weight limit of MRI table)
  • Pregnancy or breastfeeding
  • Sensitivity to imaging agents
  • Contraindications to MRI
  • Use of benzodiazepines, topiramate, doxycycline, mynocicline

Treatment and study plan

11C-PBR28

Drug

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.

Primary outcomes

  1. 11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR)

    Time frame: Baseline to 12 month

    The primary endpoint is change in mean 11C-PBR28 SUVR in multiple sclerosis patients after 1-year of ocrelizumab therapy in different brain regions.

Secondary outcomes

  1. Magnetization Transfer Ratio (MTR)

    Time frame: Baseline to 12-month

    Secondary endpoint is changes in mean magnetization transfer ratio (MTR) in cortex and normal appearing white matter (NAWM) of multiple sclerosis patients after 1-year of ocrelizumab therapy. MTR is defined as: S0 - S_MT/S0; where S0 is the signal intensity without the magnetization transfer (MT) pulse and S_MT is the signal intensity with the MT pulse. It is dimensionless because it is defined as a ratio of two signals with the same physical units, so the units cancel out. Larger MTR indicate stronger interaction between free water protons and macromolecular-bound protons.

  2. Cortical Thickness

    Time frame: Baseline to 12-month

    Secondary endpoint is changes in cortical thickness after 1-year ocrelizumab treatment in patients with multiple sclerosis.

  3. White Matter (WM) Lesion Volume

    Time frame: Baseline to 12 months

    Secondary endpoint is changes in WM lesion load after 1-year of ocrelizumab therapy in patients with MS.

Sponsors and collaborators

Lead sponsor

Massachusetts General Hospital

Other

Collaborators

  • Genentech, Inc.

Registry information

Important dates

Study start
2020
Primary completion
2024
Study completion
2025
First posted
Jan 18, 2020
Registry last updated
Dec 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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