NCT04242056

To Study the Pathophysiological Features of Multiple Sclerosis

To Study the Pathophysiological Features of Multiple Sclerosis: Combined Multi-modalities of Amyloid and Tau Images Associated With Serum Neurofilament Light Chain Levels

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Chang Gung Memorial Hospital · Academic / Other
• Sex: All
• Age: 20 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system1, whose demyelination is the pathological hallmark. MS is characterized by neuroinflammation, demyelination, axonal damage, and neurodegeneration2. The demyelination state in brain and the clinical course are difficult to predict in the early stage of disease. Recently, several neuroimaging and fluid biomarkers had been explored in MS. Using brain amyloid positron emission tomography (PET) in active MS had showed that both the damage sites and normal appearance white matter had a lower intensity than non-active MS. The result suggests a predictive role that the intensity from amyloid PET could reflect the disease activity and link to early myelin damage. The levels of tau protein in cerebrospinal fluid (CSF) had also been showed a negative correlation with brain atrophy, which is a prognostic marker for MS. In fluid biomarkers, both neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) had been used in MS and reported correlations with disease severity, the extent of neuroinflammation and progression. In current study, investigator will enroll 38 participants with MS and evaluate their clinical severity; measure the WM lesion and disease activity by magnetic resonance imaging (MRI); myelination state and amyloid deposition by amyloid PET scan; tau deposition by state of-art tau PET scan. Investigator also measure the serum levels of NfL and GFAP as the index of axonal injury and disease activity. The relationship between disease severity, brain myelination, tau deposition and serum levels of NfL will be discuss.

Conditions

• Multiple Sclerosis
• Neurofilament Light Chain
• Glial Fibrillary Acidic Protein

Interventions

Type	Name	Description
DRUG	18F-PM-PBB3	18F-PM-PBB3 brain PET studies will be conducted for 38 subjects. Dynamic PET/MRI studies will be collected by PET/MRI scanner for 100 minutes (4×15 s, 8×30 s, 960 s, 2×180 s, 8300 s, 3×600 s). Volumes of interest (VOIs) will be delineated from corresponding MR images by manual including bilateral frontal, parietal, mesial temporal, lateral temporal, hippocampal, occipital, anterior cingulate, posterior cingulate, cerebellum areas, and genu region of white matter. The DVRs will be computed from Logan graphic analysis by using cerebellum as reference input. SUVR of every cortical VOI to the gray matter of cerebellum will be calculated from nine 10-min dynamic image sets.

Timeline

• Start date: 2020-02-20
• Primary completion: 2020-09-30
• Completion: 2020-09-30
• First posted: 2020-01-27
• Last updated: 2020-01-27