NCT04634994

Brief Summary

The investigators propose to use the novel SV2a-PET ligand, \[F-18\]SDM-8 to assess synaptic density in progressive multiple sclerosis (PMS) (including primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS)), given its improved imaging characteristics and potential for large scale applicability. The specific aims of the study are: Aim 1: To compare the cortical and subcortical grey matter synaptic density in PMS patients, patients with relapsing-remitting MS (RRMS), and healthy subjects, using a novel \[F-18\] labeled synaptic density PET ligand, \[F-18\]SDM8, also known as \[F-18\]SynvesT-1. Aim 2: To compare the relationship of synaptic density PET and standard 3T MRI measures including global and regional brain atrophy and lesion load with clinical measures of physical disability, cognitive impairment, fatigue and depression in MS patients. Aim 3: To assess the relationship of synaptic density PET with serum neurofilament light chain (NfL) and with serum measurements of inflammatory markers, IL-1β, TNF-α, IL-6, MCP-1 (Monocyte Chemoattractant Protein-1) and MIF-1 (Macrophage Migration Inhibitory Factor-1).

Trial Health

77
On Track

Trial Health Score

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

Enrollment
30

participants targeted

Target at P75+ for early_phase_1 multiple-sclerosis

Timeline
8mo left

Started May 2025

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 Progress63%
May 2025Dec 2026

First Submitted

Initial submission to the registry

November 9, 2020

Completed
9 days until next milestone

First Posted

Study publicly available on registry

November 18, 2020

Completed
4.5 years until next milestone

Study Start

First participant enrolled

May 14, 2025

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

January 9, 2026

Status Verified

January 1, 2026

Enrollment Period

1.6 years

First QC Date

November 9, 2020

Last Update Submit

January 7, 2026

Conditions

Multiple Sclerosis

Keywords

Multiple SclerosisMSSynaptic DensityPositron Emission TomographyPET

Outcome Measures

Primary Outcomes (1)

  • PET measurements in individuals with PMS, RRMS, and healthy controls

    To compare PET measurements including standardized uptake value (SUV) and standardized uptake value ratio (SUVR) in individuals with PMS, RRMS, and healthy controls.

    Baseline

Secondary Outcomes (1)

  • Correlations between PET measurements and clinical, MRI, and blood and serum measures

    Baseline

Study Arms (1)

PMS, RRMS, and Healthy Control Subjects

EXPERIMENTAL
Drug: [F-18]SDM-8

Interventions

[F-18]SDM-8DRUG

PET radiopharmaceutical. Subjects will undergo \[F-18\]SDM-8 PET Scanning to measure synaptic density.

PMS, RRMS, and Healthy Control Subjects

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Subjects meeting the definition for MS (including PPMS, RRMS or SPMS) by International Panel (2017 McDonald) Criteria. Age and sex-matched healthy controls will also be recruited.
  • 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
  • Corticosteroid treatment in the past four weeks

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (9)

  • Tourdias T, Dousset V. Neuroinflammatory imaging biomarkers: relevance to multiple sclerosis and its therapy. Neurotherapeutics. 2013 Jan;10(1):111-23. doi: 10.1007/s13311-012-0155-4.

    PMID: 23132327BACKGROUND

  • Mendoza-Torreblanca JG, Vanoye-Carlo A, Phillips-Farfan BV, Carmona-Aparicio L, Gomez-Lira G. Synaptic vesicle protein 2A: basic facts and role in synaptic function. Eur J Neurosci. 2013 Dec;38(11):3529-39. doi: 10.1111/ejn.12360. Epub 2013 Sep 16.

    PMID: 24102679BACKGROUND

  • Cai Z, Li S, Matuskey D, Nabulsi N, Huang Y. PET imaging of synaptic density: A new tool for investigation of neuropsychiatric diseases. Neurosci Lett. 2019 Jan 19;691:44-50. doi: 10.1016/j.neulet.2018.07.038. Epub 2018 Jul 31.

    PMID: 30075287BACKGROUND

  • Wegner C, Esiri MM, Chance SA, Palace J, Matthews PM. Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology. 2006 Sep 26;67(6):960-7. doi: 10.1212/01.wnl.0000237551.26858.39.

    PMID: 17000961BACKGROUND

  • Mandolesi G, Grasselli G, Musumeci G, Centonze D. Cognitive deficits in experimental autoimmune encephalomyelitis: neuroinflammation and synaptic degeneration. Neurol Sci. 2010 Nov;31(Suppl 2):S255-9. doi: 10.1007/s10072-010-0369-3.

    PMID: 20635112BACKGROUND

  • Di Filippo M, Portaccio E, Mancini A, Calabresi P. Multiple sclerosis and cognition: synaptic failure and network dysfunction. Nat Rev Neurosci. 2018 Oct;19(10):599-609. doi: 10.1038/s41583-018-0053-9.

    PMID: 30158590BACKGROUND

  • Friese MA. Widespread synaptic loss in multiple sclerosis. Brain. 2016 Jan;139(Pt 1):2-4. doi: 10.1093/brain/awv349. No abstract available.

    PMID: 26747852BACKGROUND

  • Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001 Sep;50(3):389-400. doi: 10.1002/ana.1123.

    PMID: 11558796BACKGROUND

  • Weiner HL. The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann Neurol. 2009 Mar;65(3):239-48. doi: 10.1002/ana.21640.

    PMID: 19334069BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

SynVesT-1

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

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
early 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

November 9, 2020

First Posted

November 18, 2020

Study Start

May 14, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Last Updated

January 9, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)