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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2023
• Main ID: NCT05147532
• Date of registration: 15/10/2021
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Remyelination in Multiple Sclerosis: a PET-MR Longitudinal Study Investigating Individual Profiles of Myelin Repair and the Contribution of Neuroinflammation SMARTinMS
• Scientific title: Remyelination in Multiple Sclerosis: a PET-MR Longitudinal Study Investigating Individual Profiles of Myelin Repair and the Contribution of Neuroinflammation
• Date of first enrolment: January 24, 2022
• Target sample size: 80
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05147532
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

France

Contacts

• Name: Céline LOUAPRE, MD

• Name: Bruno STANKOFF, MD

Key inclusion & exclusion criteria

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).



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Inflammatory Disease

Intervention(s)

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

Primary Outcome(s)

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]

Secondary Outcome(s)

Remyelination level in rodents demyelinated by lysolecithin and grafted with single patient's lymphocytes quantified at week 3 post-graft [Time Frame: 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]

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]

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]

Secondary ID(s)

APHP200056

2021-002334-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors