Remyelination in Multiple Sclerosis: a PET-MR longitudinal study investigating individual profiles of myelin repair and the contribution of neuroinflammation (SMART in MS)

Phase 3

Recruiting

Conditions: Remyelination in Multiple Sclerosis

Interventions: Procedure: PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714

Registration Number: 2024-512761-13-00

Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary: Multiple Sclerosis (MS) is an inflammatory disease where the immune cells invade the central nervous system and destroy an essential element of nerve conduction: the myelin. An interesting feature observed in some patients is a regenerative process, called remyelination, which leads to the production of new myelin. However, the extent of remyelination is very heterogeneous among patients, only a minority of patients show a really efficient repair process along the disease course. In this project, our aim is to explore in vivo the biological mechanisms leading to a successful remyelination in some patients and to a failure in remyelination in others. With this purpose in mind we propose to develop a translational research platform where patients with multiple sclerosis will be investigated in vivo for their potential of remyelination through a follow-up with recently developed imaging technologies using a synergistic combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) to visualize and quantify myelin and neuroinflammation. In parallel blood immune cells from patients will be sampled and profiled to investigate how they could influence remyelination. This part will consist in i) grafting patients' lymphocytes in experimental rodent models of demyelination to characterize how they could promote or inhibit remyelination; ii) performing a functional and multi-omics analysis of peripheral macrophages and analyse relationships with remyelination profiles; iii) profiling T lymphocytes at the single cell level to associate specific subpopulation of the T cells with the remyelination potential assessed in patients with MRI/PET images and in grafted animals.

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruiting

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714	PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714	PET-MRI with \[18F\]-Florbetaben and PET-MRI with \[18F\]-DPA-714

Primary Outcome Measures

Name	Time	Method
Proportion of lesional demyelinated voxels at baseline that are classified as remyelinating at month 6 of multiple sclerosis patients during the relapsing and the progressive phases of the disease	Month 6	the percentage of lesional voxels classified as demyelinated on baseline \[18F\]-Florbetaben PET, that subsequently become normally myelinated on the \[18F\]-Florbetaben PET performed at 6 months, which attest remyelination

Secondary Outcome Measures

Name	Time	Method
Remyelination level in rodents demyelinated by lysolecithin and grafted with single patient's lymphocytes quantified at week 3 post-graft	Baseline
the percentage of voxels classified as significantly activated compared to control white matter, and the number/proportion of MS lesions classified as activated based on [18F]-DPA-714 PET	At baseline	To define the individual inflammatory profiles from \[18F\]-DPA-714 PET (regional individual maps of \[18F\]-DPA-714 binding) of MS patients during the relapsing and the progressive phases of the disease
Proportion of lesions that persist as chronic active at month 3 post graft over the total number of lesions induced in the rodent demyelinating models by grafting patients' lymphocytes	Baseline, at 3 Months
Proportion of each lymphocyte cluster identified from the single cell sequencing of T lymphocytes over the total T lymphocyte population for each patient	Baseline

Trial Locations

Locations (3): Groupe Hospitalier Nord Essonne
🇫🇷
Orsay, France
Assistance Publique Hopitaux De Paris
🇫🇷
Paris, France
Institut Du Cerveau Et De La Moelle Epiniere
🇫🇷
Paris, France
Groupe Hospitalier Nord Essonne
🇫🇷Orsay, France
Michel BOTTLAENDER
Site contact
0169867712
michel.bottlaender@cea.fr