Background-Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis (MS); however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications against each other and placebo in patients with MS-related fatigue.Methods-In this randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, patients with MS who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic MS centers in the US.

Background Vitamin D insufficiency is a risk factor for MS, and patients don’t always show the expected response to vitamin D supplementation. Objective To determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in MS patients and healthy controls (HCs). Methods Participants in this open-label study were female, white, aged 18–60 years, had 25(OH)D levels ≤ 75 nmol/L at screening, and had RRMS or were HCs. Participants received 5,000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors. Results 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs 23.6 kg/m2, p=0.035). 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/L (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared to HCs. Conclusions MS patients had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders.

ObjectivesWe evaluated the effect of riluzole versus placebo added to weekly IM interferon beta-1a in early multiple sclerosis (MS).MethodsThis is a randomized (1:1), double-blind, placebo-controlled trial of riluzole 50 mg twice daily in subjects with MS onset less than 1 year prior. Trial participation was up to 3 years. The primary endpoint was change in percent brain volume change. Secondary endpoints included changes in normalized gray and normal-appearing white matter volumes, retinal nerve fiber layer thickness (RNFL), MS Functional Composite and Symbol Digit Modalities Test scores. Mixed model regression analysis was used to compare the changes over time between groups.ResultsForty-three subjects were randomized to study drug (22 riluzole, 21 placebo). Baseline characteristics were overall similar between groups except for older age (P = 0.042), higher normalized cerebrospinal fluid volume (P = 0.050), lower normalized gray matter volume (P = 0.14), and thinner RNFL (P = 0.043) in the riluzole group. In the primary analysis, percent brain volume change in the placebo group decreased at a rate of 0.49% per year whereas the riluzole group decreased by 0.86% per year (0.37% more per year; 95% CI −0.78, 0.024; P = 0.065). Although age did not influence the rate of brain volume decline, the difference between groups was attenuated after adjustment for baseline normalized gray matter and lesion volume (0.26% more per year in riluzole group; 95% CI −0.057, 0.014; P = 0.22). Analyses of secondary outcomes showed no differences between groups.InterpretationThis trial provides class 1 evidence that riluzole treatment does not meaningfully reduce brain atrophy progression in early MS.

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