Multiple SclerosisPhase 4NCT04230174
Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation
A Phase 4 study testing 11C-PBR28 in people with Multiple Sclerosis, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- 11C-PBR28
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Dec 2020to 30 Apr 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- Pregnancy or breastfeeding
- Sensitivity to imaging agents
- Contraindications to MRI
- Use of benzodiazepines, topiramate, doxycycline, mynocicline
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
About this study
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.
Read more
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.
- Conditions
- Multiple Sclerosis
- Being tested
- 11C-PBR28
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-PBR28Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Multiple sclerosis patients | Experimental | Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. Receives: Drug: 11C-PBR28 |
What is being measured
The primary outcome is the main question the study is designed to answer.
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR)
The primary endpoint is change in mean 11C-PBR28 SUVR in multiple sclerosis patients after 1-year of ocrelizumab therapy in different brain regions.
Measured: Baseline to 12 month
Secondary outcomes (3)
Magnetization Transfer Ratio (MTR)
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.
Measured: Baseline to 12-month
Cortical Thickness
Secondary endpoint is changes in cortical thickness after 1-year ocrelizumab treatment in patients with multiple sclerosis.
Measured: Baseline to 12-month
White Matter (WM) Lesion Volume
Secondary endpoint is changes in WM lesion load after 1-year of ocrelizumab therapy in patients with MS.
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start29 Dec 2020
- Primary completion9 Oct 2024
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 24 multiple sclerosis patients
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Caterina Mainero, Massachusetts General Hospital
- Investigators
- Caterina Mainero, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04230174
- Sponsor's protocol ID
- 2019P002865
- Status last verified
- Dec 2025
- First submitted
- 13 Jan 2020
- Last updated
- 30 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation
- ClinicalTrials.gov ID
- NCT04230174
- Acronym / sponsor ID
- 2019P002865
- Conditions
- Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 29 Dec 2020 (actual)
- Primary completion
- 9 Oct 2024 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Posted 30 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 24 multiple sclerosis patients
| Arm | Type | Receives |
|---|---|---|
| Multiple sclerosis patients | Experimental | Drug: 11C-PBR28Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- Hypersensitivity to trial medications
- History of life-threatening reaction to Ocrelizumab
- Acute or uncontrolled chronic medical condition
- Impaired hearing
- Claustrophobia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 11C-PBR28This 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. | Drug | Multiple sclerosis patients |
Primary outcome
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.
3 secondary outcomes
Magnetization Transfer Ratio (MTR)
Time frame: Baseline to 12-month
Cortical Thickness
Time frame: Baseline to 12-month
White Matter (WM) Lesion Volume
Time frame: Baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caterina Mainero, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 11C-PBR28 in people with Multiple Sclerosis, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) (time frame: Baseline to 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.