Azathioprine

Canada has one of the highest rates of multiple sclerosis (MS). MS patients experience disabling motor, visual, and sensory symptoms, and a high risk of comorbid major depressive disorder (MDD) and severe fatigue. The lifetime prevalence of MDD in MS patients is about 50%, and nearly 90% experience severe fatigue, both of which are not responsive to typical treatments. Repetitive transcranial magnetic stimulation (rTMS) is a first line, Health Canada approved non-invasive neurostimulation treatment for MDD. rTMS induces electrical activity in the cortex using magnetic fields generated outside of the head to drive neuronal firing in the target site. However, MS is typically an exclusion criterion due to safety concerns. The goal of this clinical trial is to learn if repeated transcranial magnetic stimulation (rTMS) can be used to treat depression symptoms in adults with multiple sclerosis (MS). rTMS is a non-invasive form of brain stimulation that uses magnetic pulses to stimulate specific parts of the brain. The main questions it aims to answer are: Is rTMS safe, tolerable, and feasible to deliver as a treatment for depression and fatigue symptoms in individuals with MS? Does rTMS show preliminary effectiveness in improving depression and fatigue symptoms in this population? Researchers will determine whether rTMS treatment improves mood, fatigue, and cognition across time points (baseline, after treatment, and 4-week follow-up). Participants will: Complete screening, questionnaires, clinical assessments, cognitive tests, a brain MRI to help tailor the TMS treatment, and receive daily TMS sessions for 5 consecutive days, including: Pre-TMS brain mapping, five rTMS treatments (3 minutes) per day, separated by one hour. A safety and tolerability questionnaire will be administered daily. Complete post-treatment assessments (questionnaires, cognitive tests, psychiatric evaluation). Complete a 4-week follow-up visit, in person or virtually. Wear a fitness tracking watch during the study so researchers can collect activity data remotely. About 20 people will take part in this study through the University of Calgary.

This study compared two educational methods. Participants were assigned to participate in a 360-degree experience or a slideshow presentation. The 360-degree video group included a brain and MS program. The comparison group was given a slideshow presentation with the same information. Participants viewed the 360-degree program or the slideshow presentation only once. The online-based materials consisted of a demographic form (age, gender, race and ethnicity, and name of school), knowledge questionnaires, and an experiential learning scale. Pre-intervention, participants were asked about demographic information, whether they had previous experience with MS, the science classes they completed in high school and college, and their knowledge of the human brain and MS pathophysiology. At both pre- and post-intervention, participants completed the Multiple Sclerosis Magnetic Resonance Imaging Knowledge Questionnaire (MSMRIKQ) and the Multiple Sclerosis Knowledge Questionnaire (MSKQ). At post-intervention, participants completed a lesson experiential questionnaire about their experience viewing either the 360-degree video or the slideshow presentation. Permission to use the three instruments was obtained from their respective copyright holders.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation and systemic immune activation. Obesity is common among individuals with RA and is associated with increased disease activity, reduced treatment response, and worse functional outcomes. Inflammation in adipose tissue, driven in part by activation of the NLRP3 inflammasome and downstream gasdermin D (GSDMD)-mediated pathways, may contribute to systemic inflammation and RA disease severity. Disulfiram (DSF), an FDA-approved medication for alcohol use disorder, has recently been identified as an inhibitor of GSDMD-mediated inflammatory signaling and pyroptosis. Preclinical studies suggest that DSF reduces inflammasome activation, inflammatory cytokine release, and metabolic dysfunction. This study is a 12-week, randomized, double-blind, placebo-controlled pilot trial designed to evaluate the safety, tolerability, and preliminary efficacy of DSF in overweight and obese adults with active RA despite stable disease-modifying antirheumatic drug (DMARD) therapy. Participants will be randomized to receive either DSF (250 mg daily) or placebo. The primary objective is to assess safety and tolerability. Secondary and exploratory objectives include evaluating the effects of DSF on systemic inflammation, RA disease activity, metabolic parameters, and adipose tissue inflammasome activation. Findings from this study will inform the feasibility and design of larger clinical trials targeting GSDMD-mediated inflammation in RA.

Canada urgently needs new ways to provide rheumatology care that improve treatment and make it easier for people to get high-quality care. E-health technology is a new and promising way to do this, but it hasn't been studied much yet in rheumatology. The investigators will test a new way to help people with rheumatoid arthritis at four clinics in Quebec. This study will check if the new approach is easy to use, fits well into the clinics' daily routine, and if both patients and healthcare workers find it helpful and acceptable. This new approach involves nurses helping patients check their own health from home using an online platform. 104 adults who have rheumatoid arthritis and who have had a flare-up or a change in their medication in the last three months, will participate. Some will start using the online self-monitoring tool right away for 16 months, while others will continue with their usual care for 8 months before trying the tool. During the time they use the tool, they will fill out monthly online questionnaires to check their health. A rheumatology nurse will review their answers, suggest any needed care, provide personalized health information, and be available to answer questions through messages. This new way of care, where nurses help patients monitor their rheumatoid arthritis from home, helps make better use of limited specialist time. It's more convenient for patients, especially those who live far away, and helps meet their needs between regular doctor visits while keeping the quality of care high.

The main purpose of this study is to assess whether hyperpolarized carbon imaging in relapsing remitting multiple sclerosis (MS) patients can be used to predict response to anti-CD20 disease modifying therapy. Study procedures will include magnetic resonance imaging (MRI) assessments with a hyperpolarized pyruvate sequence, clinical assessment as well as blood markers of disease progression. This method of imaging utilizes the Warburg effect, where innate immune cells utilize a metabolic shift to glycolysis instead of oxidative phosphorylation. In pre-clinical data, increased hyperpolarized lactate production has been found to be associated with increased microglial/macrophage infiltration in the brain. Although hyperpolarized carbon imaging in humans has been established and used in the field of oncology, this will be one of the first applications of hyperpolarized carbon the study of neuroinflammation in humans. We predict that hyperpolarized carbon imaging may have the potential to monitor and evaluate neuroinflammation in MS, and in particular the innate immune activation state that plays a role in MS progression. This imaging method may provide non-invasive monitoring of disease progression and therapy response for MS patients.

The purposes of this study are to: 1) compare baseline muscle and cardiovascular health in older individuals (\>60 years old) diagnosed with MS to age-matched people without MS, 2) determine muscle and whole body changes to an exercise training program, 3) determine if the muscle in a more affected leg in individuals diagnosed with MS is different from the muscle of a less affected leg, and 4) if or how individuals diagnosed with MS adapt differently than age-matched people without MS to exercise training. Participation in this study will average 1.5 hours per visit, 3 visits per week, for approximately 4 months.

The goal of this clinical trial is to evaluate if the study drug will reduce brain and retinal atrophy by reducing inflammation and subsequently slowing neurodegeneration in people with Multiple Sclerosis. The main outcome for the trial is change in normalized brain parenchymal volume (nBPV), measured by magnetic resonance imaging (MRI). Researchers will compare outcomes from participants randomized to the study drug, versus participants randomized to placebo, to see if there are signs of slowed neurodegeneration (i.e., reduction in brain and retinal atrophy).

People with neurological conditions often have difficulty walking, including problems such as foot drop. Functional electrical stimulation (FES) is a treatment that uses electrical signals to activate muscles and support walking. The L300 device is designed to help lift the foot during each step. This study will evaluate how using the L300 affects walking performance. Researchers will measure walking speed, step length, and walking symmetry using objective gait assessment tools. The study will also explore whether people with different neurological conditions respond differently to FES. The goal of this research is to improve understanding of how FES influences walking and to support more personalized rehabilitation approaches.

The goal of this clinical trial is to learn if the time an individual eats each day impacts neurological health in people with multiple sclerosis. The main questions the investigators are asking are: 1. Does meal timing affect biomarkers of neuronal health (neurofilament light chain \[NfL\] and BDNF) and inflammation (IL-6, IL-17, TNF-ɑ) in adults with MS. 2. Does meal timing affect expression of circadian clock genes and genes associated with autophagy in adults with MS. Participants will be instructed to start and stop eating at specific times each day based on their group assignment and their personal schedule. They will respond to prompts sent to them on their smartphone to record the times they start and stop eating each day. As a secondary goal, the study will also explore the feasibility of including translocator protein (TSPO)-PET imaging of neuroinflammation in future clinical trials of TRE in people with MS. To accomplish this, imaging will be completed in a subset of 8 participants at the beginning and end of the study.

The purpose of this study is to assess and compare how well multiple sclerosis (MS) patients tolerate cetirizine versus diphenhydramine as a pre-medication before receiving anti-CD20 infusion therapy of ocrelizumab, ublituximab or rituximab. The study will also compare the safety of cetirizine versus diphenhydramine as a pre-medication for preventing infusion reactions in MS patients receiving anti-CD20 infusion therapy.

This proposal aims to conduct a 10-week randomized controlled trial comparing walking and resistance training with and without computerized cognitive training in older Veterans with Multiple Sclerosis, followed by 12 months of fall tracking with sensors and fall calendars. The primary objectives of this proposed CDA2 are to provide critical preliminary data on 1) the feasibility of conducting a 10-week RCT, 2) preliminary treatment effects on gait, cognition, and falls, and 3) neuroinflammatory biomarkers. Dr. Katherine Hsieh will receive hands-on training in the design and conduct of clinical trials (Dr. Hackney), mechanisms underlying physical activity, cognitive rehabilitation, and falls (Drs. Twamley, Hackney, \& Kesar), fall detection technology (Prof. Sanford), and clinical problems faced by MS participants (Dr. Backus) to achieve her long-term career goal of becoming an independent falls prevention investigator.

Multiple sclerosis (MS) is a common disease of the central nervous system that affects almost 1 million people in the United States. However, diagnosing MS can be difficult and often leads to misdiagnosis. More sensitive and specific biomarkers are needed to help with the diagnosis, prognosis, and evaluation of treatment response for MS. The central vein sign (CVS) and the paramagnetic rim lesion (PRL) are two biomarkers that have shown promise in improving diagnostic accuracy for MS. The goal of this study is to provide pilot information on the long-term performance of the CVS and PRL to help diagnose and follow people with MS. The study will follow 40 participants over 48 months to determine if the CVS and PRL help make a diagnosis of MS and how they can be used to follow people with MS. The study will also examine how PRL and CVS change over 48 months. The results of this pilot study will inform the development of a grant application to extend 5-year follow-up for all 420 participants of the CAVS-MS study. The study will use high-resolution T2\*-weighted MRI to detect the CVS and PRLs. An MRI of the brain with contrast will be used to examine CVS, PRL and longitudinal analysis of lesions that slowly grow over time (slowly expanding lesions \[SELs\]). The results of this study have the potential to improve the accuracy of diagnosing and treating MS.