Demyelination and Remyelination in Multiple Sclerosis (MS) Detected by Brain Amyloid PET-CT

NCT05783934 | Completed

• 1 other identifier: CE 2585
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial study is to evaluate the presence of relationships between PET and MRI images indicative of chronic inflammatory activity (smoldering plaques), apparent absence of inflammatory activity (silent plaques without microglial rim), or indicative of more recent inflammatory activity, in contrast-enhanced areas or in T2/Flair-positive areas of not distant onset in patients diagnosed with progressive (secondary or primary) stage multiple sclerosis and in patients in relapse and remission. Laboratory analysis of serum markers will be performed: neuronal and glial cytoskeletal proteins (e.g., Nf-L, pN-FH, GFAP), and the levels of neurotrophic factors (e.g., BDNF, GDNF) and cytokines (e.g., TNFα, IL-6, IL-1β, interferon) will be evaluated.

Conditions

Multiple Sclerosis

Keywords

MRI; 18F-Florbetaben PET/CT

Outcome Measures

Primary Outcomes (1)

• PET outcome

  The main endpoint is to differentiate PET outcome in progressive forms compared to relapsing-remitting forms. It is expected that in RRMS forms, the degree of demyelination and of remyelination is lower and higher, respectively, than in progressive forms.

  this evaluation is performed at the time of recruitment

Secondary Outcomes (1)

• correlation between PET data and MRI images and degree of disability

  this evaluation is performed at the time of recruitment

Study Arms (1)

18F-Florbetaben PET/CT scan

EXPERIMENTAL

All the partecipants will undergo PET/CT scan evaluation after 18F-florbetaben administration

Diagnostic Test: 18F-florbetaben PET/CT

Interventions

18F-florbetaben PET/CT DIAGNOSTIC_TEST

The PET/CT study will be performed using a dual time acquisition protocol consisting of an early acquisition and a late acquisition. Early acquisition Early acquisition starts with the patient already positioned on the PET/CT bed and venous access available. A low-dose CT scan is performed for attenuation correction, the PET acquisition is started in list mode and a couple of seconds after the start, 300 MBq of 18F-Florbetaben is administered followed by washing with 10 ml of saline. Early acquisition will last 30 minutes. Late acquisition A low-dose CT scan is performed to correct for attenuation and anatomical localisation, followed by a 20-minute list mode PET acquisition so that images are acquired after 90 minutes (tolerance: +10 minutes) of radiopharmaceutical uptake.

18F-Florbetaben PET/CT scan

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• progressive stage of multiple sclerosis (both secondary and primary, SMP)
• patients in relapsing-remitting multiple sclerosis (RRMS)

You may not qualify if:

• a disability greater than 7
• patients with a cognitive impairment interfering with full study participation (Minimental score less than 24)
• patients with internal medical problems that in the opinion of the investigator may interfere with full participation and collaboration
• inability to undergo MRI or PET examinations
• ongoing pregnancy and lactation

Sponsors & Collaborators

• Istituti Clinici Scientifici Maugeri SpA: lead

Study Sites (1)

ICS Maugeri SpA SB IRCCS

Pavia, PV, 27100, Italy

Location

Related Publications (14)

• Absinta M, Sati P, Masuzzo F, Nair G, Sethi V, Kolb H, Ohayon J, Wu T, Cortese ICM, Reich DS. Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo. JAMA Neurol. 2019 Dec 1;76(12):1474-1483. doi: 10.1001/jamaneurol.2019.2399.

  PMID: 31403674 BACKGROUND

• 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 BACKGROUND

• Absinta M, Lassmann H, Trapp BD. Mechanisms underlying progression in multiple sclerosis. Curr Opin Neurol. 2020 Jun;33(3):277-285. doi: 10.1097/WCO.0000000000000818.

  PMID: 32324705 BACKGROUND

• Bagnato F, Gauthier SA, Laule C, Moore GRW, Bove R, Cai Z, Cohen-Adad J, Harrison DM, Klawiter EC, Morrow SA, Oz G, Rooney WD, Smith SA, Calabresi PA, Henry RG, Oh J, Ontaneda D, Pelletier D, Reich DS, Shinohara RT, Sicotte NL; NAIMS Cooperative. Imaging Mechanisms of Disease Progression in Multiple Sclerosis: Beyond Brain Atrophy. J Neuroimaging. 2020 May;30(3):251-266. doi: 10.1111/jon.12700.

  PMID: 32418324 BACKGROUND

• Stankoff B, Poirion E, Tonietto M, Bodini B. Exploring the heterogeneity of MS lesions using positron emission tomography: a reappraisal of their contribution to disability. Brain Pathol. 2018 Sep;28(5):723-734. doi: 10.1111/bpa.12641.

  PMID: 30020560 BACKGROUND

• Bodini B, Stankoff B. PET is necessary to make the next step forward in understanding MS pathophysiology - Yes. Mult Scler. 2019 Jul;25(8):1086-1087. doi: 10.1177/1352458519828298. Epub 2019 Feb 27. No abstract available.

  PMID: 30810071 BACKGROUND

• Hogel H, Rissanen E, Vuorimaa A, Airas L. Positron emission tomography imaging in evaluation of MS pathology in vivo. Mult Scler. 2018 Oct;24(11):1399-1412. doi: 10.1177/1352458518791680. Epub 2018 Aug 9.

  PMID: 30091657 BACKGROUND

• Calvi A, Haider L, Prados F, Tur C, Chard D, Barkhof F. In vivo imaging of chronic active lesions in multiple sclerosis. Mult Scler. 2022 Apr;28(5):683-690. doi: 10.1177/1352458520958589. Epub 2020 Sep 23.

  PMID: 32965168 BACKGROUND

• Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurol. 2018 Oct 1;75(10):1215-1224. doi: 10.1001/jamaneurol.2018.1836.

  PMID: 30014145 BACKGROUND

• Chincarini A, Peira E, Morbelli S, Pardini M, Bauckneht M, Arbizu J, Castelo-Branco M, Busing KA, de Mendonca A, Didic M, Dottorini M, Engelborghs S, Ferrarese C, Frisoni GB, Garibotto V, Guedj E, Hausner L, Hugon J, Verhaeghe J, Mecocci P, Musarra M, Queneau M, Riverol M, Santana I, Guerra UP, Nobili F. Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC). Neuroimage Clin. 2019;23:101846. doi: 10.1016/j.nicl.2019.101846. Epub 2019 May 4.

  PMID: 31077984 BACKGROUND

• Bodini B, Veronese M, Garcia-Lorenzo D, Battaglini M, Poirion E, Chardain A, Freeman L, Louapre C, Tchikviladze M, Papeix C, Dolle F, Zalc B, Lubetzki C, Bottlaender M, Turkheimer F, Stankoff B. Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis. Ann Neurol. 2016 May;79(5):726-738. doi: 10.1002/ana.24620.

  PMID: 26891452 BACKGROUND

• Kaunzner UW, Kang Y, Zhang S, Morris E, Yao Y, Pandya S, Hurtado Rua SM, Park C, Gillen KM, Nguyen TD, Wang Y, Pitt D, Gauthier SA. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain. 2019 Jan 1;142(1):133-145. doi: 10.1093/brain/awy296.

  PMID: 30561514 BACKGROUND

• Mehta V, Pei W, Yang G, Li S, Swamy E, Boster A, Schmalbrock P, Pitt D. Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions. PLoS One. 2013;8(3):e57573. doi: 10.1371/journal.pone.0057573. Epub 2013 Mar 14.

  PMID: 23516409 BACKGROUND

• Absinta M, Sati P, Fechner A, Schindler MK, Nair G, Reich DS. Identification of Chronic Active Multiple Sclerosis Lesions on 3T MRI. AJNR Am J Neuroradiol. 2018 Jul;39(7):1233-1238. doi: 10.3174/ajnr.A5660. Epub 2018 May 3.

  PMID: 29724768 BACKGROUND

Related Links

• Radiation exposure by \[F18\]Florbetaben, a new PET tracer for detection of cerebral β-amyloid in Caucasian and Asian healthy volunteers

MeSH Terms

Conditions

Multiple Sclerosis

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

• Giuseppe Trifirò, MD

  ICS Maugeri Spa SB IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 24, 2023
• Study Start: July 27, 2021
• Primary Completion: November 15, 2023
• Study Completion: January 9, 2024
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

IT (1)