NCT02649985

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. 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. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
250

participants targeted

Target at P75+ for phase_1 multiple-sclerosis

Timeline
20mo left

Started May 2016

Longer than P75 for phase_1 multiple-sclerosis

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
May 2016Dec 2027

First Submitted

Initial submission to the registry

January 6, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 8, 2016

Completed
4 months until next milestone

Study Start

First participant enrolled

May 2, 2016

Completed
11.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Last Updated

January 28, 2026

Status Verified

January 1, 2026

Enrollment Period

11.7 years

First QC Date

January 6, 2016

Last Update Submit

January 27, 2026

Conditions

Multiple SclerosisAlzheimer's Disease

Outcome Measures

Primary Outcomes (1)

  • Standardized uptake values (SUV)/Standardized uptake value ratios (SUVR)

    PET imaging measurement

    Baseline, 3 months, and 6 months

Study Arms (7)

Relapsing-Remitting Multiple Sclerosis

EXPERIMENTAL

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.

Drug: [F-18]PBR06Drug: [C-11]PBR28

Progressive Multiple Sclerosis

EXPERIMENTAL

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.

Drug: [F-18]PBR06

Alzheimer's Disease

EXPERIMENTAL

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.

Drug: [F-18]PBR06

Healthy Control

EXPERIMENTAL

This group will serve as non disease population.

Drug: [F-18]PBR06

Multiple Sclerosis Ocrelizumab

EXPERIMENTAL

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.

Drug: [F-18]PBR06

Multiple Sclerosis Foralumab

EXPERIMENTAL

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.

Drug: [F-18]PBR06

Multiple Sclerosis Steroids Treatment

EXPERIMENTAL

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.

Drug: [F-18]PBR06

Interventions

[F-18]PBR06DRUG

PET radiopharmaceutical

Also known as: [F-18] PBR06
Alzheimer's DiseaseHealthy ControlMultiple Sclerosis ForalumabMultiple Sclerosis OcrelizumabMultiple Sclerosis Steroids TreatmentProgressive Multiple SclerosisRelapsing-Remitting Multiple Sclerosis
[C-11]PBR28DRUG

PET radiopharmaceutical

Also known as: [C-11] PBR28
Relapsing-Remitting Multiple Sclerosis

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • For SPMS, deterioration in EDSS score in the last year is required.
  • 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.
  • For the Foralumab arm, patients enrolled in approved IRB protocols (2021P000105, 2022P000005, 2022P001075) will be enrolled.
  • 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.
  • AD subjects with MMSE score of 20-26.
  • Subjects willing to undergo PET and MRI imaging
  • Subjects willing and able to give informed consent

You may not qualify if:

  • Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
  • Individuals with bipolar disease and schizophrenia
  • Concurrent medical conditions that contraindicate study procedures.
  • 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.
  • Claustrophobia
  • Non-MRI compatible implanted devices
  • 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.
  • \. For the Ocrelizumab arm, steroids arm, and longitudinal arm, subjects with abnormal serum creatinine will be excluded.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brigham MS Center, 60 Fenwood Road

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (1)

  • Singhal T, Cicero S, Rissanen E, Ficke J, Kukreja P, Vaquerano S, Glanz B, Dubey S, Sticka W, Seaver K, Kijewski M, Callen AM, Chu R, Carter K, Silbersweig D, Chitnis T, Bakshi R, Weiner HL. Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study. Clin Nucl Med. 2024 Jun 1;49(6):491-499. doi: 10.1097/RLU.0000000000005201. Epub 2024 Apr 17.

    PMID: 38630948DERIVED

MeSH Terms

Conditions

Multiple SclerosisAlzheimer Disease

Interventions

3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesDementiaBrain DiseasesCentral Nervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

3-Hydroxysteroid DehydrogenasesHydroxysteroid DehydrogenasesAlcohol OxidoreductasesOxidoreductasesEnzymesEnzymes and CoenzymesNAD (+) and NADP (+) Dependent Alcohol Oxidoreductases

Study Officials

  • Tarun Singhal, MD

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tarun Singhal, MD

CONTACT

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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Neurology

Study Record Dates

First Submitted

January 6, 2016

First Posted

January 8, 2016

Study Start

May 2, 2016

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Last Updated

January 28, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)