Role of Microglial Activation and Norepinephrine Transporter Abnormalities in Pathogenesis of MS-related Fatigue

NCT04144257 | Completed Phase 1 FDA Drug

• 1 other identifier: 2019P002356
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching aim is to assess the role of microglial activation and norepinephrine transporter binding in pathogenesis of MS-related fatigue, using novel Positron Emission Tomography (PET) radiotracers, \[F-18\]PBR06 and \[C-11\]MRB. Specific Aims: Specific Aim 1: To determine the relationship of cerebral microglial activation, as assessed by \[F-18\]PBR06 PET, with MS-related fatigue. Specific Aim 2: To determine the relationship of norepinephrine transporter (NET) binding, as assessed by \[C-11\]MRB PET, with MS-related fatigue. Specific Aim 3: To determine the relationship of microglial activation and NET binding, with grey matter pathology (lesion load and brain atrophy) assessed using 7T MRI, and evaluate their independent contribution in development of MS-related fatigue.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• Standardized Uptake Value Ratio (SUVR)

  PET outcome measure for \[F-18\]PBR06 radioligand used to quantify microglial activation.

  Baseline

• Area Under the Curve Ratio (AUCR)

  PET outcome measure for \[C-11\]MeNer radioligand used to quantify norepinephrine transporter binding in brain regions of interest (e.g, putaminal, pallidal, and white matter).

  Baseline

Secondary Outcomes (2)

• Correlations between Modified Fatigue Impact Scale (MFIS) and PET outcome measures

  Baseline

• Correlations between Expanded Disability Status Scale (EDSS) and PET outcome measures

  Baseline

Study Arms (1)

Subjects diagnosed with multiple sclerosis

EXPERIMENTAL

We plan to enroll 12 subjects with multiple sclerosis (6 with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis).

Drug: [F-18]PBR06; Drug: [C-11]Methylreboxetine

Interventions

[F-18]PBR06 DRUG

PET radiopharmaceutical. Subjects will undergo \[F-18\]PBR06-PET (microglial activation).

Also known as: [18F]PBR06

Subjects diagnosed with multiple sclerosis

[C-11]Methylreboxetine DRUG

PET radiopharmaceutical. Subjects will undergo \[C-11\]MRB-PET (norepinephrine transporter binding).

Also known as: [C-11]MRB

Subjects diagnosed with multiple sclerosis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects meeting the definition for RRMS or SPMS by International Panel (2017 McDonald) Criteria.
• We will recruit patients with RRMS, recently diagnosed in the last 2 years. There will be no disease modifying therapy restrictions for RRMS or SPMS patients.
• Male and female subjects age 18 to 60 years.
• Patients able to withhold medication that may interfere with C-11\[MRB\] radiotracer uptake for 24 hours before the scan.

You may not qualify if:

• Relapse/Corticosteroid treatment in the past 4 weeks to avoid transient effects on imaging
• 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
• Low affinity binders

Sponsors & Collaborators

• U.S. Army Medical Research Acquisition Activity: collaborator
• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham MS Center, 60 Fenwood Road

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Tarun Singhal, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• 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: October 28, 2019
• First Posted: October 30, 2019
• Study Start: March 12, 2020
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)