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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05633875

Collaborator

(none)

Enrollment

5.5

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis (MS)	Other: MRI

Detailed Description

MS patient already included in previous studies using MRI and/or PET-MR (INFLASEP (NCT02305264), FLUMATEP (NCT01651520) or SHADOWTEP) will be proposed a long-term follow up study.

Participants will undergo :

a full neurological examination including EDSS
medical history and comorbidities (including smoking)
concomitant and MS treatments
neuropsychological testing
Blood sample for serum biobanking
multimodal MRI

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Other

Time Perspective:

Other

Official Title:

Multimodal Imaging Signatures of the Biological Mechanisms Underlying Neurodegeneration in Multiple Sclerosis: Long Term Predictive Value (IMAGIN-DEAL in MS)

Anticipated Study Start Date :

Jan 30, 2025

Anticipated Primary Completion Date :

Jan 30, 2025

Anticipated Study Completion Date :

Jul 15, 2025

Outcome Measures

Primary Outcome Measures

EDSS (Expanded Disability Status Scale) score [Inclusion]
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

Secondary Outcome Measures

MSFC (Component of the Multiple Sclerosis Functional Score) score for neurological disability: 9-Hole Peg Test (9HPG) [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=300
SDMT(Symbol Digit Modalities Test) for speed processing [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=110
T25FW (Timed 25 Foot Walk test) [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=180
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]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS)
10/36 Spatial Recall tests [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=30
RL/RI-16 memory test [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=100
Backward and forward verbal digit span test [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=48
Stroop test [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=100
Deno 80 test [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS). Scale: min=0 ;max=80
White matter lesion load on MRI [Inclusion]
predictive value of imaging signatures (chronic active lesions, remyelination and prelesion areas) on the progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS)
Whole brain, white matter, deep grey matter and cortical atrophy on MRI [Inclusion]
Progression between baseline (inclusion in a first study: FLUMATEP, INFLASEP or SHADOWTEP) and follow up (IMAGIN-DEAL in MS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator: Bruno Stankoff, Pr, Assistance Publique - Hôpitaux de Paris
Study Director: Olivier Colliot, Mr, ARAMIS team (ICM) - Hospital Pitié-Salpêtrière