Recruiting
Phase 1
Phase 2

Brain Imaging

Sponsor:

Brigham and Women's Hospital

Code:

NCT02649985

Conditions

Multiple Sclerosis

Alzheimer's Disease

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

[F-18]PBR06

[C-11]PBR28

Study Details

Brief summary:

The specific aims of the study are:

Primary: To determine the presence and regional distribution of microglial activation, as assessed by Fluorine-18 (18F) labeled "Peripheral Benzodiazepine Receptor 06" (PBR06) -PET, in subjects with active Relapsing Remitting Multiple Sclerosis (RRMS), Secondary Progressive Multiple Sclerosis (SPMS), and Alzheimer's Disease (AD) as compared to healthy controls

Secondary:

1. To assess the relationship between microglial activation and clinical variables including disease severity and comorbidities (such as pain, fatigue and/or depression), as well as clinical MRI findings (such as lesions and atrophy)
2. A pilot substudy aims to establish the non-inferiority of \[F-18\]PBR06 as compared with Carbon-11 \[C-11\] labeled "Peripheral Benzodiazepine Receptor 28" (PBR28) PET in patients with RRMS.

Hypothesis: The working hypothesis is that there is microglial activation in multiple sclerosis and Alzheimer's disease as compared to healthy controls and that the pattern/ regional distribution of microglial activation is different in Multiple Sclerosis (MS) versus AD and correlates with disease severity and comorbidities.

In addition, the investigators hypothesize that \[F-18\]PBR06-PET scans will be at least as good as \[C-11\]PBR28-PET scans, the current gold standard.

Conditions

Multiple Sclerosis

Alzheimer's Disease

Study ID

NCT02649985

Start date

May 2, 2016

Status verified date

Jan, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

1. Male and female subjects age 18 to 70 years. For Alzheimer's Disease patients and healthy controls, the age range is going to be 18 to 85 years. This is because Alzheimer's disease subjects are usually older and it'd be difficult to recruit Alzheimer's patients who are younger than 70 years. Multiple Sclerosis, on the other hand, is a disease of a younger population.
2. For RRMS, it needs to be active, which is defined as at least one relapse in the past 12 months, at least one gadolinium enhancing lesion on MRI within 12 months of enrollment or at least one new FLAIR bright lesion on MRI within 6 months of enrollment.
3. For SPMS, deterioration in EDSS score in the last year is required.
4. For the subjects in the Ocrelizumab arm, only the subjects who have already been prescribed Ocrelizumab by their treating MS neurologist but have not yet started the first infusion, will be included.
5. For the Foralumab arm, patients enrolled in approved IRB protocols (2021P000105, 2022P000005, 2022P001075) will be enrolled.
6. For the steroids arm, only subjects who have already been prescribed steroids by their treating MS neurologist, but have not yet initiated treatment, will be included.
7. AD subjects with MMSE score of 20-26.
8. Subjects willing to undergo PET and MRI imaging
9. Subjects willing and able to give informed consent

Exclusion Criteria:

1. Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
2. Individuals with bipolar disease and schizophrenia
3. Concurrent medical conditions that contraindicate study procedures.
4. Women who are pregnant or nursing. Also, any woman who is seeking to become pregnant or suspects she is pregnant will be excluded from enrollment.
5. Claustrophobia
6. Non-MRI compatible implanted devices
7. For the Ocrelizumab arm, subjects already on Ocrelizumab will be excluded. 8. For the steroids arm, subjects who have already started steroid treatment will be excluded.

9\. For the Ocrelizumab arm, steroids arm, and longitudinal arm, subjects with abnormal serum creatinine will be excluded.

Study Design

Enrollment

250 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: Relapsing-Remitting Multiple Sclerosis

Subjects meeting the definition for RRMS by the International Panel Criteria, who are active, as defined by at least one MS relapse in the past 12 months, at least one gadolinium enhancing lesion on a MRI within 12 months of enrollment, or at least one new FLAIR bright lesion on MRI within 6 months of enrollment.

The study will be performed in two phases. In the early pilot phase, 8 subjects with multiple sclerosis will undergo both \[C-11\]PBR28 PET scan and \[F-18\]PBR06 PET scan. At the end of this phase, a formal interim analysis will be performed and if imaging characteristics of \[F-18\]PBR06 are found non-inferior to or better than \[C-11\]PBR28, the rest of the study will be completed using \[F-18\]PBR06. On the other hand, if \[F-18\]PBR06 is found to be inferior to \[C-11\]PBR28, the rest of the study will be pursued using \[C-11\]PBR28.

experimental: Progressive Multiple Sclerosis

Subjects meeting the definition for SPMS/PPMS (Primary Progressive Multiple Sclerosis) by International Panel Criteria and who have demonstrated deterioration in EDSS score in last 1 year.

experimental: Alzheimer's Disease

Subjects meeting the definition for probable AD based on NINDS-ADRDA criteria. In terms of severity of disease, the investigators will select subjects with mild AD, as defined by Mini-Mental Status Examination (MMSE) score of 20-26.

experimental: Healthy Control

This group will serve as non disease population.

experimental: Multiple Sclerosis Ocrelizumab

Subjects who have already been prescribed Ocrelizumab by their treating MS neurologist, but have not yet started the first Ocrelizumab infusion.

Subjects will undergo two separate visits for \[F-18\]PBR06 PET scans, once before starting Ocrelizumab and the second visit 3 months after completion of the initial Ocrelizumab doses.

experimental: Multiple Sclerosis Foralumab

Subjects will undergo 3 separate visits for \[F-18\]PBR06 PET scans, once before initiating treatment with Foralumab, the second visit 3 months after starting Foralumab, and the third visit 6 months after starting Foralumab.

experimental: Multiple Sclerosis Steroids Treatment

Subjects who have already been prescribed steroids by their treating MS neurologist, but have not yet initiated treatment.

Subjects will undergo two separate visits for \[F-18\]PBR06 PET scans: one before steroid treatment and one after steroid treatment.

Interventions

[F-18]PBR06

PET radiopharmaceutical

[C-11]PBR28

PET radiopharmaceutical

Primary outcome measure

  • Standardized uptake values (SUV)/Standardized uptake value ratios (SUVR) [ Time Frame: Baseline, 3 months, and 6 months ]

Central Contacts and Locations

Central contacts

Tarun Singhal, MD

617-264-3043tsinghal@bwh.harvard.edu

Locations

Brigham MS Center, 60 Fenwood Road

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Steven Cicero

617-264-3044scicero@bwh.harvard.edu

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Jan 28, 2026

Last verified

Jan, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2026-01-28.