Smoldering Inflammation in MS

April 27, 2026 updated by: Matthew Brier, Washington University School of Medicine

Investigation of Smoldering Inflammation in Multiple Sclerosis

The goal of this observational study is to learn about inflammation in those with relapsing remitting Multiple Sclerosis (MS). The main questions it aims to answer are:

  • How does abnormal neural inflammation compare to cellular and molecular inflammation in MS?
  • Once treated, why does abnormal inflammation persist?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to combine multi-tracer PET and high-resolution CSF analysis to understand the inflammatory landscape of MS and to identify components of inflammation which do not resolve with high-efficacy DMT and are hypothesized to drive disability accumulation via smoldering inflammation. Identification of components of the pathologic cascade which do not respond to extant therapies will motivate future, complementary therapies targeted at yet untreated MS pathology.

Current MS disease modifying therapies (DMT) focus on reducing the inflammatory or auto-immune component of the disease. Highly effective DMTs are incredibly effective at reducing this inflammation such that new lesions and clinical relapses are increasingly rare. However, despite these advances, most patients will experience clinical worsening independent of relapse activity. This eventually manifests as progressive MS and stubbornly resists therapy. One hypothesized driver of this clinical progression is smoldering inflammation. Smoldering inflammation is defined as ongoing inflammation sufficient to cause accumulating tissue injury but insufficient to cause clinical relapse. The nature of this smoldering inflammation is poorly understood. Emerging imaging biomarkers have identified smoldering inflammation, but those markers are not well-linked to cellular mechanisms. A key innovation of this approach is that, by comparing pre- vs. post-treatment single-cell RNA sequencing data, the researchers will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes. Identifying components of persistent inflammation may identify future treatment targets.

25 adult patients with relapsing remitting multiple sclerosis will be enrolled in this study. Patients will be recruited from the John L. Trotter MS Center at Washington University in St. Louis. Participants will be referred to the study by their treating neurologist.

[11C]-CS1P1 and [11C]-DPA-713 are the investigational radiotracers used in this study. Participation in this study consists of several visits. Visits include 1) (pre-)screening and clinical, 2) baseline lumbar puncture, 3) baseline [11C]-DPA-713 PET/CT, 4) baseline [11C]-CS1P1 PET/CT, 5) baseline [18F]-FDG PET/MRI, 6) follow-up lumbar puncture, 7) follow-up [11C]-DPA-713 PET/CT, 8) follow-up [11C]-CS1P1 PET/CT, and 9) follow-up [18F]-FDG PET/MRI. Baseline and follow-up visits of the same type (e.g., steps 3 and 7) are identical with baseline occurring at enrollment and follow-up occurring at least nine months but no more than 12 months after DMT initiation. Screening session must precede the clinical sessions. At each the baseline and follow-up time point, the lumbar puncture and each imaging session may occur in any order. At baseline and follow up, all sessions will take place within approximately 1 month. Multiple sessions can occur on the same day. Consecutive imaging sessions will be separated by 6 half-lives of the initially injected radiotracer.

This pilot study will link the molecular specificity and high spatial resolution of combined positron emission tomography and magnetic resonance imaging with the molecular explanatory power of single-cell RNA sequencing to investigate the effects of B cell depletion, or other similarly efficacious treatments, on smoldering inflammation and characterize the nature of persistent inflammation which contributes to disability in patients with MS. A key innovation of this approach is that, by comparing pre- vs. post-treatment single-cell RNA sequencing data, researchers will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes. Identifying components of persistent inflammation may identify future treatment targets.

Study Type

Observational

Enrollment (Estimated)

25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Matthew Brier, MD, PhD
  • Phone Number: 314-362-7666
  • Email: brierm@wustl.edu

Study Contact Backup

Study Locations

  • United States
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Barnes Jewish Center for Clinical Imaging Research
        • Contact:
        • Contact:
        • Principal Investigator:
          • Matthew R Brier, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

25 adult patients with relapsing remitting multiple sclerosis will be enrolled in this study. Patients will be recruited from the John L. Trotter MS Center at Washington University in St. Louis. Participants will be referred to the study by their treating neurologist.

Description

Inclusion Criteria:

  • Male or female, any race
  • Age ≥ 18 years
  • Capable of providing written informed consent for volunteering to undergo research procedures
  • Diagnosis of MS as established by the referring physician and confirmed by the Sponsor-Investigator. Only patients with active disease, defined as at least 1 enhancing lesion present in the preceding 6 months, will be enrolled
  • Treatment naïve except for relapse-related treatments such as corticosteroids or plasmapheresis,
  • Planned initiation, at the discretion of the referring physician, of a high efficacy DMT. High efficacy DMT will be defined to include ocrelizumab, natalizumab, or any MS treatment in the opinion of the Sponsor-Investigator to have similar efficacy as the named treatments
  • Clinical labs, including at least a CBC and BMP, without significant abnormality as determined by the Sponsor-Investigator or designee, within the 3 months prior to enrollment

Exclusion Criteria:

  • Presence of a low binding polymorphism for TSPO
  • Hypersensitivity to [11C]-CS1P1, [11C]-DPA-713, [18F]-FDG, or any of their excipients
  • Contraindications to PET, CT or MRI (e.g. certain incompatible electronic medical devices, inability to lie still for extended periods) that make it potentially unsafe for the individual to participate
  • eGFR less than 60 (for gadolinium)
  • Severe claustrophobia
  • Women who are currently pregnant or breast-feeding
  • Currently undergoing radiation therapy
  • Insulin dependent diabetes
  • Contraindication to lumbar puncture (LP), including use of antiplatelet therapy (other than aspirin 81mg), therapeutic anticoagulation, or space occupying intracranial mass. History of a coagulopathy is also exclusionary
  • Any condition that, in the opinion of the Sponsor-Investigator or designee could increase risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with collection of the data (e.g., renal or liver failure, advanced cancer)
  • Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed 5 rem

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Participants
Adults with MS taking part in this study.
Radiation: Radiotracer [11C]-CS1P1
Radiotracer used in PET/CT scans of the head and neck Dose range: 12-17 mCi
Radiation: Radiotracer [11C]-DPA-713
Radiotracer used in PET/CT scans of the head and neck Dose range:15-20 mCi
Drug: anti-CD20 MS treatment
MS treatment taken indepenently after initial testing
Radiation: Radiotracer [12F]-FDG
used in PET/CT scans of the head and neck Dose: 5-7 mCi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Volume of Distribution (Vt) of DPA-713 and CS1P1 and Cerebral metabolic rate of glucose (CMRglc) in white matter lesions and normal appearing white matter before and after treatment.
Time Frame: 1 year
1 year
Changes in scRNAseq measures of inflammatory cell types in the CSF before and after treatment
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Correlation between changes in Vt or CMRglc compared to changes in cell type numbers from scRNAseq
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 19, 2024

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

September 7, 2024

First Submitted That Met QC Criteria

September 7, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202403168

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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