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

September 11, 2023 updated by: Assistance Publique - Hôpitaux de Paris
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Paris, France, 75013
        • Recruiting
        • CIC Neurosciences - Hôpital Pitié Salpêtrière
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

RRMS patients:

  1. Age between 18 and 55 years old
  2. RRMS according to the 2017 Mc Donald criteria
  3. Less than 5 years of disease duration
  4. At least 9 supra-tentorial white matter lesions on T2/FLAIR MRI
  5. Last treatment with methylprednisolone should have been performed at least 1 month before PET examinations
  6. Interferon-beta, glatiramere acetate and oral first line therapy will such as dimethylfumarate or teriflunomide will be admitted
  7. Affiliation to a social security scheme or beneficiary of such a scheme (Except "Aide Médicale d'Etat")

Progressive MS patients:

  1. Age between 18 and 55 years old
  2. Progressive MS (primary or secondary progressive MS) according to the 2017 Mc Donald criteria
  3. Less than 10 years of disease duration in the progressive phase
  4. At least 9 supra-tentorial white matter lesions on T2/FLAIR MRI
  5. Interferon-beta, glatiramere acetate and oral first line therapy will such as dimethylfumarate or teriflunomide will be admitted
  6. Affiliation to a social security scheme or beneficiary of such a scheme (except "Aide Médicale d'Etat")

Healthy volunteers:

  1. Age between 18 and 55 years old
  2. Without any evolutive pathology
  3. Able to understand the study objectives and procedures
  4. Affiliation to a social security scheme or beneficiary of such a scheme (except "Aide Médicale d'Etat")

Exclusion Criteria:

For all participants:

  1. 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)
  2. PET for clinical research already done within the last 12 months
  3. Low Affinity Binding profile (TSPO polymorphism analyzed at screening visit)
  4. Pregnancy, breast-feeding, lack of efficient contraception
  5. Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary or cardiac disease, or any other chronic neurological diseases
  6. Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
  7. Know hypersensitivity to Myelin PET : [18F]-Florbetaben
  8. Patient under legal protection

Additional exclusion criteria for patients:

  1. 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.
  2. Known allergy to gadoteric acid
  3. Allergies (seafood, pollinosis, urticarial) having required a medical intervention
  4. Severe renal insufficiency (creatinine clearance < 60mL/min).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714
Procedure: PET-MRI with [18F]-Florbetaben and PET-MRI with [18F]-DPA-714
PET-MRI: 2 at baseline visits (V0 and V1) and 1 at M6

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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
Month 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
At baseline
Proportion of each lymphocyte cluster identified from the single cell sequencing of T lymphocytes over the total T lymphocyte population for each patient
Time Frame: Baseline
Baseline
Remyelination level in rodents demyelinated by lysolecithin and grafted with single patient's lymphocytes quantified at week 3 post-graft
Time Frame: Baseline
Baseline
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
Time Frame: Baseline, at 3 Months
Baseline, at 3 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 24, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 7, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP200056
  • 2021-002334-16 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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