Investigating Myelin Repair in Multiple Sclerosis Using Advanced Imaging

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

This study is trying to understand how some people with Multiple Sclerosis can repair their nerve coverings better than others by using advanced imaging techniques to look closely at their brains over time.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: alemtuzumab, natalizumab, cyclophosphamide
• Locations: 1 site (Paris)
• Trial ID: NCT05147532 on ClinicalTrials.gov

What this trial studies

This study aims to explore the biological mechanisms behind remyelination in patients with Multiple Sclerosis (MS) by utilizing advanced imaging techniques, specifically a combination of magnetic resonance imaging (MRI) and positron emission tomography (PET). It focuses on understanding why some patients experience successful remyelination while others do not, by following patients longitudinally and assessing their individual profiles. The study will include both relapsing-remitting and progressive forms of MS, with specific eligibility criteria based on age, disease duration, and MRI findings.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 55 with either relapsing-remitting or progressive forms of Multiple Sclerosis and specific MRI findings.

Not a fit: Patients outside the age range of 18 to 55 or those with more advanced disease duration may not benefit from this study.

Why it matters

Potential benefit: If successful, this research could lead to improved understanding and potential treatments for enhancing myelin repair in MS patients.

How similar studies have performed: While the approach of using PET-MRI for studying remyelination is innovative, similar studies have shown promise in understanding neuroinflammation and myelin repair.

Eligibility 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).

Where this trial is running

Paris

• CIC Neurosciences - Hôpital Pitié Salpêtrière — Paris, France (Recruiting)

Study contacts

• Study coordinator: Bruno STANKOFF, MD

Conditions Multiple Sclerosis; Inflammatory Disease; Multiple sclerosis; Remyelination; Combination of magnetic resonance imaging and positron emission tomography