Brain PET scans to detect microglial activation in people with MS and Alzheimer's.

Microglial Activation PET Brain Imaging in Multiple Sclerosis, Alzheimer's Disease, and Other Neurological and Neuropsychiatric Diseases

We will test whether an F-18 PET tracer called PBR06 (with a pilot comparison to C-11 PBR28) can detect microglial activation in people with active relapsing-remitting MS, secondary progressive MS, mild Alzheimer's, and healthy volunteers.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Drugs / interventions: Ocrelizumab, Foralumab, radiation
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT02649985 on ClinicalTrials.gov

What this trial studies

The protocol enrolls four groups (active RRMS, SPMS with recent EDSS worsening, mild AD with MMSE 20-26, and healthy controls) with a target total of 30 participants. In an initial pilot phase, eight RRMS subjects will receive both C-11 PBR28 and F-18 PBR06 PET scans followed by a formal interim analysis to determine non-inferiority of F-18 PBR06; if adequate, the remainder of the study will use F-18 PBR06. All participants will also undergo 3T brain MRI and clinical characterization to relate PET signal to lesions, atrophy, disability, and symptoms such as pain, fatigue, and depression. The primary goal is to map presence and regional distribution of microglial activation versus healthy controls, with secondary aims linking PET findings to clinical and MRI measures.

Who should consider this trial

Good fit: Ideal candidates are adults (MS participants 18–70 years; Alzheimer's patients and healthy controls up to 85 years) with active RRMS (recent relapse or new/enhancing MRI lesion), SPMS with recent EDSS worsening, or mild AD (MMSE 20–26), as well as healthy volunteers.

Not a fit: Patients without active disease features, with more advanced dementia than allowed, with contraindications to PET/MRI (including pregnancy), or unable to travel to the Boston site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could provide a noninvasive biomarker to map brain inflammation and help track disease activity or guide treatment decisions.

How similar studies have performed: Previous studies using TSPO-targeting tracers such as C-11 PBR28 have detected microglial activation in MS and AD, while F-18 PBR06 is less established and is being evaluated here against PBR28 in a pilot.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts

• Brigham MS Center, 60 Fenwood Road — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Tarun Singhal, MD — Brigham and Women's Hospital
• Study coordinator: Tarun Singhal, MD

Conditions Multiple Sclerosis; Alzheimer's Disease