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Multiple SclerosisSMARTinMSNCT05147532

Remyelination in Multiple Sclerosis: a PET-MR Longitudinal Study Investigating Individual Profiles of Myelin Repair and the Contribution of Neuroinflammation

A study testing PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714 in people with Multiple Sclerosis and Inflammatory Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Multiple Sclerosis, Inflammatory Disease
What is being tested?
PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteFrance
Study dates
24 Jan 2022to May 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • RRMS patients:
  • Age between 18 and 55 years old
  • RRMS according to the 2017 Mc Donald criteria
  • Less than 5 years of disease duration
  • At least 9 supra-tentorial white matter lesions on T2/FLAIR MRI
  • Last treatment with methylprednisolone should have been performed at least 1 month before PET examinations
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  • Interferon-beta, glatiramere acetate and oral first line therapy will such as dimethylfumarate or teriflunomide will be admitted
  • Affiliation to a social security scheme or beneficiary of such a scheme (Except "Aide Médicale d'Etat")
  • Progressive MS patients:
  • Age between 18 and 55 years old
  • Progressive MS (primary or secondary progressive MS) according to the 2017 Mc Donald criteria
  • Less than 10 years of disease duration in the progressive phase
  • At least 9 supra-tentorial white matter lesions on T2/FLAIR MRI
  • Interferon-beta, glatiramere acetate and oral first line therapy will such as dimethylfumarate or teriflunomide will be admitted
  • Affiliation to a social security scheme or beneficiary of such a scheme (except "Aide Médicale d'Etat")
  • Healthy volunteers:
  • Age between 18 and 55 years old
  • Without any evolutive pathology
  • Able to understand the study objectives and procedures
  • Affiliation to a social security scheme or beneficiary of such a scheme (except "Aide Médicale d'Etat")

Who cannot join

  • For all participants:
  • 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)
  • PET for clinical research already done within the last 12 months
  • Low Affinity Binding profile (TSPO polymorphism analyzed at screening visit)
  • 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
Show all 14Show fewer
  • Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
  • Know hypersensitivity to Myelin PET : [18F]-Florbetaben
  • Patient under legal protection
  • Additional exclusion criteria for patients:
  • Treatment with cyclophosphamide, mitoxantrone, fingolimod, cladribine, alemtuzumab, anti CD20 antibodies or natalizumab will not be admitted. These treatments may be administered after the Baseline visit.
  • Known allergy to gadoteric acid
  • Allergies (seafood, pollinosis, urticarial) having required a medical intervention
  • Severe renal insufficiency (creatinine clearance < 60mL/min).

Trial locations and contacts

1 site in 1 country.

Bruno STANKOFF, MD contact

0171970659

bruno.stankoff@aphp.fr

France1 site, 1 recruiting

  • CIC Neurosciences - Hôpital Pitié Salpêtrière

    Paris, 75013

    Céline LOUAPRE, MD, celine.louapre@aphp.fr

    Recruiting

Other trials in France

About this study

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.

Being tested
PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714
Keywords
Multiple sclerosis, Remyelination, Combination of magnetic resonance imaging (MRI) and positron emission tomography (PET)
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714Procedure or surgery

    PET-MRI: 2 at baseline visits (V0 and V1) and 1 at M6

Study groups in NCT05147532
Study groupRoleWhat they receive
PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714OtherPET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714
Receives: Procedure: PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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

    Measured: Month 6

Secondary outcomes (4)

  1. 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

    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

    Measured: At baseline

  2. Proportion of each lymphocyte cluster identified from the single cell sequencing of T lymphocytes over the total T lymphocyte population for each patient

    Measured: Baseline

  3. Remyelination level in rodents demyelinated by lysolecithin and grafted with single patient's lymphocytes quantified at week 3 post-graft

    Measured: Baseline

  4. 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

    Measured: Baseline, at 3 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2021
  2. Study start24 Jan 2022
  3. Primary completionOct 2023 (estimated)
  4. Study completionMay 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05147532
Sponsor's protocol ID
APHP200056
Other IDs
2021-002334-16
Acronym
SMARTinMS
Status last verified
Sep 2023
First submitted
15 Oct 2021
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Bodini B, Tonietto M, Airas L, Stankoff B. Positron emission tomography in multiple sclerosis - straight to the target. Nat Rev Neurol. 2021 Nov;17(11):663-675. doi: 10.1038/s41582-021-00537-1. Epub 2021 Sep 20.

    PubMed 34545219

  • Poirion E, Tonietto M, Lejeune FX, Ricigliano VAG, Boudot de la Motte M, Benoit C, Bera G, Kuhnast B, Bottlaender M, Bodini B, Stankoff B. Structural and Clinical Correlates of a Periventricular Gradient of Neuroinflammation in Multiple Sclerosis. Neurology. 2021 Apr 6;96(14):e1865-e1875. doi: 10.1212/WNL.0000000000011700. Epub 2021 Mar 18.

    PubMed 33737372

  • Auvity S, Tonietto M, Caille F, Bodini B, Bottlaender M, Tournier N, Kuhnast B, Stankoff B. Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB. Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):490-501. doi: 10.1007/s00259-019-04516-z. Epub 2019 Nov 4.

    PubMed 31686177

  • 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.

    PubMed 30020560

  • 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.

    PubMed 26891452

  • Stankoff B, Freeman L, Aigrot MS, Chardain A, Dolle F, Williams A, Galanaud D, Armand L, Lehericy S, Lubetzki C, Zalc B, Bottlaender M. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-(1)(1)C]-2-(4'-methylaminophenyl)- 6-hydroxybenzothiazole. Ann Neurol. 2011 Apr;69(4):673-80. doi: 10.1002/ana.22320. Epub 2011 Feb 18.

    PubMed 21337603

Questions about this trial

What is this clinical trial studying?

A study testing PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714 in people with Multiple Sclerosis and Inflammatory Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Bruno STANKOFF, MD (0171970659, bruno.stankoff@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05147532, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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