The primary objective of this study is to investigate the cognitive benefits of ozanimod in individuals with Multiple Sclerosis (MS). The study aims to understand the neural basis of cognitive improvement in Relapsing-Remitting MS patients under ozanimod treatment using neuroimaging and behavioral techniques to characterize the brain and behavioral changes due to ozanimod treatment.
To assess MS patients' cognitive improvement while on ozanimod, the investigators will compare MS patients' baseline performance to the patients' performance following treatment on memory, processing speed, verbal ability and executive function. The investigators predict that cognitive performance will improve during the ozanimod treatment compared to the baseline. Baseline-treatment differences will be assessed using repeated-measures analysis of covariance (ANCOVA) while also controlling for effects of age, education, disease duration, and expanded disability status score (EDSS). The investigators predict that improved cognitive performance will be accompanied by improvements in brain structure (e.g., increased whole brain volume) and function metrics. Thus, each MS patients' brain volume, white matter connectivity, lesion load, and resting BOLD at baseline, during treatment, and after ozanimod treatment will be measured. For each structure and function MR metric, baseline-treatment differences will be assessed using repeated-measures ANCOVA while also controlling for effects of age, education, disease duration, EDSS and brain parenchymal fraction (the ratio of functional brain tissue to whole brain volume).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
A hard capsule that is taken daily for one year.
Center for Brain Health
Dallas, Texas, United States
Change in Processing Speed/Symbol-Digit Modality Test (SDMT) Performance
SDMT is a neuropsychological assessment of processing speed in MS. The SDMT consists of 9 symbols that correspond to a number. Participants have 90 seconds to complete as many symbol to number associations as they can. Scoring is based on how many they can complete correctly in the span of 90 seconds. Therefore, to assess MS patients' cognitive changes while on ozanimod, MS patients' baseline performance to their performance following treatment on processing speed will be compared. The primary endpoint for this study will be a change from baseline in written SDMT performance of at least 4 points.
Time frame: 1 year
Change in Volumetric Blood-Oxygen-Level-Dependent (BOLD) signal as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
To assess the mechanisms by which ozanimod changes processing speed in MS, fMRI measures will be obtained, including the patients' volumetric BOLD signal. To assess metrics of MS patients' structural and functional changes while on ozanimod, MS patients' resting BOLD will be measured. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics. Each MS patients' resting BOLD signal will be measured at baseline, during treatment, and after ozanimod treatment. Additionally, BOLD signal of ozanimod-responders to non-responders will be compared.
Time frame: 1 year
Change in Cerebral Blood Flow (CBF) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' CBF during the treatment phase will be assessed for comparison to baseline. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Time frame: 1 year
Change in Cerebral Metabolic Rate of Oxygen (CMRO2) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
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To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' CMRO2 and CBF/CMRO2 ratio (i.e., NVC) will be assessed during the treatment phase for comparison to baseline. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Time frame: 1 year
Change in Whole Brain Volume as Measured By Structural Magnetic Resonance Imaging
To assess metrics of MS patients' structural and functional changes while on ozanimod, the investigators will measure MS patients' brain volume. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Time frame: 1 year
Differences in Diffusion parameters of ozanimod-responders to non-responders as Measured By a Diffusion Kurtosis Resonance Imaging (DKI)
To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' diffusion parameters of ozanimod-responders to non-responders will be assessed.
Time frame: 1 year