Multiple SclerosisPhase 1/2NCT04144257

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

A Phase 1/2 study testing [F-18]PBR06 and [C-11]Methylreboxetine in people with Multiple Sclerosis, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Multiple Sclerosis
What is being tested?: [F-18]PBR06 and [C-11]Methylreboxetine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 12 Mar 2020to 13 Apr 2021
Phase: Phase 1/2

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 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham MS Center, 60 Fenwood Road
Boston, Massachusetts, 02115

Other trials in United States

About this study

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.

Read the detailed description

Design: This is a single center, cross-sectional study of patients with multiple sclerosis, who will each, undergo both, [C-11]MRB-PET (norepinephrine transporter binding) and [F-18]PBR06-PET (microglial activation), in addition to 7 Tesla brain MRIs. Patients will also undergo cross-sectional estimations of blood markers.

Genotype Testing:

Blood sample drawn on the initial screening visit will be used to obtain genomic DNA for genotyping for polymorphism within the TSPO gene on chromosome 22q13.2, using a Taqman assay. High affinity and medium affinity binders will be included while the low affinity binders will be excluded from the study.

PET Scanning:

During the PET scan visits, all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection. The radiotracers will be produced using standardized procedures. At the time of imaging, the subjects will be positioned in the gantry of a high-resolution PET/CT camera. Head alignment will be made, relative to the canthomeatal line, using projected laser lines whose positions are known with respect to the slice positions of the scanner. A head support apparatus will be used to minimize head motion.Dynamic data over 120 minutes for PET quantification will be acquired, according to previously described methods for both tracers.

MRI Scanning:

High resolution MRI scanning will be performed using the 7T Siemens MAGNETOM Terra MRI unit at Brigham \& Women's Hospital (BWH).

Serum assays:

Serum measurements for inflammatory markers and relevant neurochemicals will be performed according to established procedures.

Clinical Data

The following non-imaging, clinical data will be obtained:

Modified fatigue Impact Scale (MFIS) Fatigue Severity Status Scale (FSSS) Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS)

Conditions: Multiple Sclerosis
Being tested: [F-18]PBR06, [C-11]Methylreboxetine
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[F-18]PBR06Drug
Also called [18F]PBR06
PET radiopharmaceutical. Subjects will undergo [F-18]PBR06-PET (microglial activation).
[C-11]MethylreboxetineDrug
Also called [C-11]MRB
PET radiopharmaceutical. Subjects will undergo [C-11]MRB-PET (norepinephrine transporter binding).

Study groups in NCT04144257
Study group	Role	What they receive
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). Receives: Drug: [F-18]PBR06; Drug: [C-11]Methylreboxetine

What is being measured

The primary outcome is the main question the study is designed to answer.

Standardized Uptake Value Ratio (SUVR)
PET outcome measure for [F-18]PBR06 radioligand used to quantify microglial activation.
Measured: 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).
Measured: Baseline

Secondary outcomes (2)

Correlations Between Modified Fatigue Impact Scale (MFIS) and PET Outcome Measures
MFIS is a fatigue rating scale. Scores range from 0-84. Higher values indicate worse fatigue.
Measured: Baseline
Correlations Between Expanded Disability Status Scale (EDSS) and PET Outcome Measures
EDSS is a disability rating scale. Scores range from 0-10. Higher values indicate worse clinical function.
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Mar 202013 Apr 2021

First posted30 Oct 2019
Study start12 Mar 2020
Primary completion13 Apr 2021
Study completion13 Apr 2021

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 Brigham and Women's 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 1/2
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04144257
Sponsor's protocol ID: 2019P002356
Status last verified: Sep 2026
First submitted: 28 Oct 2019
Last updated: 15 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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