Multiple sclerosis MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Mavenclad
Pharmaceutical Form: Tablet
Sponsors
Turku PET centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Signing the informed consent form -Cladribine treatment is planned and indicated and is according to label -45-55 years of age at the time of signing the research informed consent form -RRMS diagnosis in accordance with McDonald 2017 criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Patients with other neurodegenerative disease than MS -Abnormal lymphocyte counts -Patients with human immunodeficiency virus (HIV). -Patients with active chronic infection (tuberculosis or hepatitis). -Patients with active malignancy. -Patients with moderate or severe renal impairment (creatinine clearance <60 mL/min) -Patients that are pregnant or breast-feeding -Corticosteroid treatment within 4 weeks of imaging -Patients with significant abnormal findings other than MS in a previous MRI. -Patients with claustrophobia, or a history of moderate to severe anxiety disorder or panic attacks (which could potentially lead to preterm termination of the imaging) -Contraindication to PET scan investigations -Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study. -Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans. -Patients with previous alemtuzumab administration -Patients with less than 6 months since previous administration of ocrelizumab or rituximab (or with abnormal B-cell counts) -Patients with less than 1 month since previous administration of other DMT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the change in microglial cell activation in different brain areas (NAWM normal appearing grey matter and the chronic active/ smoldering (slowly expanding) lesions) before and after 18 months of treatment with cladribine evaluated with [11C]PK11195-PET-imaging.;Secondary Objective: -To compare the change in microglial activation in different brain areas before and after 18 mo of cladribine treatment evaluated with QSM-MRI. -To evaluate the total lesion load of the WM MS plaques at different time points using MRI -To measure total brain, WM and GM volumes using MRI at different time points of the study -To determine MD and FA using DTI at different time points -To correlate the baseline microglial activation to the clinical outcome parameters at 18 mo to evaluate whether high microglial activation is predictive of higher likelihood of progression and other measures of disability. -To correlate the baseline microglial activation to the MRI parameters -To compare microglial activation at baseline in the study group to microglial activation in a group of age-matched previously imaged healthy controls -To compare microglial activation in the study group to microglial activation in an independent group of previously imaged age-matched untreated MS-patients.;Primary end point(s): Change in TSPO binding in the NAWM after 18 months of cladribine treatment, measured with distribution volume ratio (DVR) of the 11C-PK11195 radioligand binding;Timepoint(s) of evaluation of this end point: baseline and 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in TSPO binding in other brain areas of interest after 18 months of cladribine treatment Change in MRI parameters after 18 months of cladribine treatment -Brain volume -White matter lesion volume -Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) -Level of QSM-positive signal at plaque edge Blood biomarkers (before and after treatment) -NFL and GFAP serum concentration -NFL and GFAP association with MRI and PET imaging findings Clinical (before and after treatment) -EDSS and MSFC -Association of EDSS and MSFC with PET, MRI and biomarker findings;Timepoint(s) of evaluation of this end point: baseline and 18 months | — |
Countries
Finland
Contacts
Public ContactTurku PET centre
Turku PET centre
Outcome results
None listed