Multimodal Imaging Signatures of the Biological Mechanisms Underlying Neurodegeneration in Multiple Sclerosis

NCT05633875 | Recruiting

• 1 other identifier: APHP220766
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterised by multi-focal inflammatory and demyelinating lesions disseminated in the brain and in the spinal cord. Impressive advancements in the treatment of the autoimmune component of the disease have been achieved during the last decades, leading to a drastic reduction of white matter lesion accumulation and relapse rate along the disease course. However, the development of treatments effective for preventing or delaying the neurodegenerative component of the disease, that underly disability accrual and progression of the disease, remains a major challenge. The development of novel therapeutic strategies for neuroprotection that target all patients with MS is a priority objective for research in the next years. The critical steps towards identifying treatments that prevent neuro-axonal damage include a deep understanding of the mechanisms underlying neurodegeneration and the development of reliable biomarkers for assessing the efficacy of emerging drugs and for accelerating their translation to clinical use. The team of Prof. Stankoff has pioneered an innovative imaging approach combining positron emission tomography and MRI, and succeeded in generating individual maps or key biological processes such as endogenous remyelination, neuroinflammation, or early damage preceding lesion formation. Using these approaches, it has been shown that these mechanisms were influencing disability worsening over the disease course, but the investigators still lack long term longitudinal studies for the validation of these advanced imaging metrics as prognosis markers. Recently, preliminary results have also suggested that a multimodal combination of advanced MRI sequences may have the potential to reproduce some PET results. In this project the investigators propose to unravel the predictive value of individual maps of tremyelination, neuroinflammation, and early tissue damage, on long term disability worsening and to develop a novel imaging approach that aims to capture remyelination of lesions, ongoing inflammation invisible on T1 and T2 MRI sequences (subacute/chronic active lesions) and to predict short-term future disease activity (identify prelesional areas), from a single multimodal MRI acquisition in patients with MS.

Conditions

Multiple Sclerosis (MS)

Keywords

Multiple sclerosis (MS); MRI; RRMS; long term predictive value; PET-MRI

Outcome Measures

Primary Outcomes (1)

• EDSS (Expanded Disability Status Scale) score

  predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression of neurological disability between the first inclusion in FLUMATEP, INFLASEP or SHADOWTEP study, and the inclusion in the current study. Scale: min=0 ;max=10

  Inclusion

Secondary Outcomes (11)

• MSFC (Component of the Multiple Sclerosis Functional Score) score for neurological disability: 9-Hole Peg Test (9HPG)

  Inclusion

• SDMT(Symbol Digit Modalities Test) for speed processing

  Inclusion

• T25FW (Timed 25 Foot Walk test)

  Inclusion

• MSFC (component of the Multiple Sclerosis Functional Score) score for neurological disability: PASAT (Paced Auditory Serial Addition Test) 3 sec for speed processing. Scale: min=0 ;max=60

  Inclusion

• 10/36 Spatial Recall tests

  Inclusion

Interventions

MRI OTHER

Patients will undergo MRI without contrast agent

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

Major subjects with Multiple Sclerosis will be included in this study

You may qualify if:

• Multiple Sclerosis Patient already enrolled in one of those 3 protocols since 8 years or more: INFLASEP, FLUMATEP 1-2 or SHADOWTEP
• Adult patient
• Affiliation to a social security scheme or beneficiary of such a scheme (Except "Aide Médicale d'Etat")
• Consent obtained

You may not qualify if:

• Any reasons, which does not allow to perform MRI, including claustrophobia, the implant of a pace maker or the presence of an intra-ocular foreign body (a contra- indication questionnaire will be filled in beforehand)
• Pregnancy, breast-feeding, lack of efficient contraception
• Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary or cardiac disease, or any other chronic neurological diseases
• Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
• Enrolment in another interventional study protocol for the duration of his or her participation without physician's agreement
• Patient under legal protection

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

CIC Neurosciences

Paris, 75013, France

RECRUITING

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

• Bruno Stankoff, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Olivier Colliot, Mr

  ARAMIS team (ICM) - Hospital Pitié-Salpêtrière

  STUDY DIRECTOR

Central Study Contacts

Bruno Stankoff, MD

CONTACT

1 42 16 24 32; bruno.stankoff@aphp.fr

Fredy Pene, Mr

CONTACT

1 49 28 20 00; fredy.pene@aphp.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 1, 2022
• Study Start: April 25, 2023
• Primary Completion (Estimated): June 25, 2026
• Study Completion (Estimated): June 25, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

FR (1)