Smoldering Inflammation in MS

NCT06591429 | Recruiting FDA Drug

• 1 other identifier: 202403168
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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?

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Imaging; Inflammation

Outcome Measures

Primary Outcomes (2)

• 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.

  1 year

• Changes in scRNAseq measures of inflammatory cell types in the CSF before and after treatment

  1 year

Secondary Outcomes (1)

• Correlation between changes in Vt or CMRglc compared to changes in cell type numbers from scRNAseq

  1 year

Study Arms (1)

Participants

Adults with MS taking part in this study.

Radiation: Radiotracer [11C]-CS1P1; Radiation: Radiotracer [11C]-DPA-713; Drug: anti-CD20 MS treatment; Radiation: Radiotracer [12F]-FDG

Interventions

Radiotracer [11C]-DPA-713 RADIATION

Radiotracer used in PET/CT scans of the head and neck Dose range:15-20 mCi

Participants

anti-CD20 MS treatment DRUG

MS treatment taken indepenently after initial testing

Participants

Radiotracer [11C]-CS1P1 RADIATION

Radiotracer used in PET/CT scans of the head and neck Dose range: 12-17 mCi

Participants

Radiotracer [12F]-FDG RADIATION

used in PET/CT scans of the head and neck Dose: 5-7 mCi

Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Barnes Jewish Center for Clinical Imaging Research

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (7)

• Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

  PMID: 28002679 RESULT

• Maggi P, Sati P, Nair G, Cortese ICM, Jacobson S, Smith BR, Nath A, Ohayon J, van Pesch V, Perrotta G, Pot C, Theaudin M, Martinelli V, Scotti R, Wu T, Du Pasquier R, Calabresi PA, Filippi M, Reich DS, Absinta M. Paramagnetic Rim Lesions are Specific to Multiple Sclerosis: An International Multicenter 3T MRI Study. Ann Neurol. 2020 Nov;88(5):1034-1042. doi: 10.1002/ana.25877. Epub 2020 Sep 9.

  PMID: 32799417 RESULT

• Endres CJ, Pomper MG, James M, Uzuner O, Hammoud DA, Watkins CC, Reynolds A, Hilton J, Dannals RF, Kassiou M. Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. J Nucl Med. 2009 Aug;50(8):1276-82. doi: 10.2967/jnumed.109.062265. Epub 2009 Jul 17.

  PMID: 19617321 RESULT

• Brier MR, Hamdi M, Rajamanikam J, Zhao H, Mansor S, Jones LA, Rahmani F, Jindal S, Koudelis D, Perlmutter JS, Wong DF, Nickels M, Ippolito JE, Gropler RJ, Schindler TH, Laforest R, Tu Z, Benzinger TLS. Phase 1 Evaluation of 11C-CS1P1 to Assess Safety and Dosimetry in Human Participants. J Nucl Med. 2022 Nov;63(11):1775-1782. doi: 10.2967/jnumed.121.263189. Epub 2022 Mar 24.

  PMID: 35332093 RESULT

• Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25.

  PMID: 23007702 RESULT

• Hemond CC, Baek J, Ionete C, Reich DS. Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical status in multiple sclerosis: A retrospective cross-sectional study. Mult Scler. 2022 Nov;28(13):2046-2056. doi: 10.1177/13524585221102921. Epub 2022 Jun 24.

  PMID: 35748669 RESULT

• Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015 Feb;14(2):183-93. doi: 10.1016/S1474-4422(14)70256-X.

  PMID: 25772897 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood and spinal fluid

MeSH Terms

Conditions

Multiple Sclerosis; Inflammation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Matthew Brier, MD, PhD

CONTACT

314-362-7666; brierm@wustl.edu

Nicole Shelley, MA

CONTACT

314-730-0516; nshelley@wustl.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology Adult, Neuroimmunology

Study Record Dates

• First Submitted: September 7, 2024
• First Posted: September 19, 2024
• Study Start: June 19, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 28, 2026

Record last verified: 2025-12

Locations

US (1)