Nisha Revirajan

Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls

Background: Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation. Objective: We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS 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 relapsing–remitting MS (RRMS) or were HCs. Participants received 5000 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: For this study 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). In total, 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 with HCs. Conclusions: Patients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders.

A randomized controlled phase II trial of riluzole in early multiple sclerosis

We evaluated the effect of riluzole versus placebo added to weekly IM interferon beta‐1a in early multiple sclerosis (MS).

Magnetic resonance imaging correlates of clinical outcomes in early multiple sclerosis

OBJECTIVES To study the association between changes in brain magnetic resonance imaging (MRI) and clinical outcomes in early MS. METHODS MS patients within 12 months of onset were enrolled and followed up to 3 years. Clinical measures included Symbol Digit Modalities Test (SDMT), MS Functional Composite (MSFC) and low contrast letter acuity (LCLA). MRI outcomes included brain volume changes measured by SIENA and SIENAX normalized measurements [brain parenchymal volume (BPV), normal-appearing white and gray matter volume (NAWMV and GMV) and T2 lesion volume (T2LV)]. Mixed model regression measured time trends and associations between imaging and clinical outcome. RESULTS Forty-three patients were enrolled within 7.5±4.9 months of onset. Baseline T2 lesion volume predicted subsequent changes in Paced Auditory Serial Addition Test (PASAT) (p=0.004), whereas baseline measures of atrophy including BPV, GMV, and NAWMV predicted longitudinal changes in MSFC (p=0.016, p=0.040, p=0.021, respectively) and Timed-25 Foot Walk (p<0.05). Each 1% decrease in SIENA was associated with 1.14 point decrease in SDMT score (p=0.03). Each 1% decrease in brain volume SIENA was associated with almost 1.5 letters decrease on LCLA (p=0.02). CONCLUSION Measures of lesion volume and overall brain volume were associated with different long-term clinical outcome measures in early MS.

Association Between Glutamate Blockade and Fatigue in Patients With Multiple Sclerosis

Association Between Glutamate Blockade and Fatigue in Patients With Multiple Sclerosis Excitotoxity, primarily mediated by excessive glutamate release, is one of the main proposed mechanisms for neurodegeneration in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis.1 However, a few clinical trials of medications with glutamate-blocking properties have not yet shown beneficial effects in patients with MS. Fatigue is one of the most frequently reported MS symptoms and the underlying mechanisms of this potentially debilitating symptom are not well understood.2 Here, we report the effects of riluzole, a medication with glutamate-blocking properties, on fatigue in a randomized clinical trial in patients with early MS.

Retinal axonal loss in very early stages of multiple sclerosis

The lack of surrogates of clinical progression has limited the design of neuroprotection trials in multiple sclerosis (MS). Our aim was to study the association between time‐domain optical coherence tomography measures and clinical and magnetic resonance imaging outcomes in early MS.

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial

BACKGROUND Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. OBJECTIVE To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. DESIGN/METHODS The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. RESULTS 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. CONCLUSIONS Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065.