Multiple Sclerosis

Approximately 50% of people with multiple sclerosis (MS) use a wheelchair within 30 years of the initial diagnosis. Wheelchair use in MS is often associated with fatigue as a consequence of muscle weakness. Indeed, fatigue, a prevalent consequence of MS, often becomes debilitating and exhausts energetic resources when carrying-out tasks of daily life and/or interacting with the community, as these require ambulatory mobility. This experience of excessive fatigue has its roots in muscle weakness and results in reliance on a wheelchair for mobility, and the dependency on a wheelchair may further reduce muscular strength, particularly of the lower extremities. We propose that wheelchair users with MS can increase muscular strength through a personalized exercise rehabilitation, and this in turn will improve ambulatory performance and possibly reduce fatigue. To date, no research has examined the effects of this specific exercise rehabilitation program (GH method) on physical function and other disease-related outcomes in persons with MS who use wheelchairs as a primary mobility device.

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.

Music therapy is widely used in relational and rehabilitation settings. In addition to Neurologic Music Therapy and other music-based techniques, "sonification" approaches were recently introduced in the field of rehabilitation. The "sonification" can be defined as a properly selected set of sonorous-music stimuli are associated with patient movements mapping. In fact, the auditory-motor feedback can replace damaged proprioceptive circuits with a consequent improvement of the rehabilitation process. Interventions with "sonification" facilitate sensorimotor learning, proprioception and movements planning and execution improving global motor parameters. This study proposes the use of musical auditory cues which includes the melodic-harmonic component of the music. This kind of sonification makes the feedback pleasant and predictable as well as potentially effective. The investigators propose to apply and assess the effectiveness of this kind of sonification on gait training and other secondary outcomes in stroke, Parkinson's disease and multiple sclerosis population. Also, the investigators will assess the impact of "sonification" on the level of fatigue perceived during the rehabilitation process and on the quality of life. The study is a multicenter randomized controlled trial and will involve 120 patients that will undergo standard motor rehabilitation or the same rehabilitation but with the sonification support. The interventions will be evaluated at the baseline, after 10 sessions, after 20 sessions and at follow-up (one month after the end of the treatment). The assessment will include functional, motor, fatigue and quality of life evaluations. The collected data will be statistically processed.

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).

This study will have two Phases: Phase 1a and Phase 1b. The goals of this clinical study are to learn more about the study drug KITE-363, by evaluating its safety, tolerability and efficacy in participants with relapsed/refractory autoimmune neurologic diseases. The primary objectives of this study are: * To evaluate the safety and tolerability of KITE-363 in participants with autoimmune neurologic diseases * To determine the recommended dose for Phase 1b. * To evaluate the preliminary efficacy of KITE-363 in participants with autoimmune neurologic diseases.

The main purpose of this study is to assess the bioequivalence of ocrelizumab SC test formulation to the marketed ocrelizumab SC reference formulation in participants with either relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). The study consists of 2 phases: a controlled phase, where participants in each group will receive one dose of test or reference formulation and a continuation phase, where all participants in both groups will receive ocrelizumab SC test formulation.

The purpose of this study is to evaluate the safety, tolerability, efficacy, and drug levels of CC-97540 in participants with Relapsing Forms of Multiple Sclerosis (RMS), Progressive Forms of Multiple Sclerosis (PMS) or Refractory Myasthenia Gravis (MG).

The primary purpose of the study is to evaluate the safety and tolerability of a single-ascending intravenous (IV) dose (Part 1), a single-ascending subcutaneous (SC) dose (Part 2), and multiple ascending SC doses (Part 3) of RO7121932 in participants with multiple sclerosis (MS).

This interventional clinical trial aims to investigate the effects of internal and external focus-based exercise training combined with cognitive dual-task training in individuals diagnosed with multiple sclerosis. The primary objective is to determine whether these exercise approaches improve gait, balance, and cognitive functions. The main research questions are: Does dual-task training combined with internal focus-based exercises improve gait, balance, and cognitive performance? Does dual-task training combined with external focus-based exercises lead to greater improvements compared to internal focus strategies? Participants will be divided into two groups, and the researchers will compare the effects of internal focus-based and external focus-based dual-task exercise training on functional outcomes. Participants will: Perform structured exercise sessions under the supervision of a physiotherapist Engage in dual-task activities by combining motor exercises with simple cognitive tasks (e.g., backward counting, word generation) Participate in an 8-week training program, with sessions held twice a week lasting approximately 45-60 minutes Undergo assessments of gait, balance, and cognitive function before and after the intervention This study does not involve invasive procedures or biological sample collection. The findings are expected to contribute to the development of more effective dual-task rehabilitation strategies for individuals with multiple sclerosis.

Inflammatory or degenerative diseases of the brain and spinal cord, such as multiple sclerosis, may be related to problems with an individual s immune system. However, more information is needed on the ways in which the cells of the immune system interact with the central nervous system (CNS). This study will compare tests performed on both healthy volunteers and individuals who have signs or symptoms of immune-related damage to their CNS. This study will include two groups of subjects at least 12 years old. Subjects will either have symptoms of immune-related CNS damage, or will be healthy volunteers selected for comparison purposes. Study participants will visit the NIH Clinical Center on an outpatient basis for an initial evaluation visit. During the visit, patients will provide a comprehensive medical history and undergo a neurological examination, and will provide blood samples for research purposes. The healthy volunteers will be asked to schedule a return visit for a magnetic resonance imaging (MRI) procedure, and may be asked to undergo other tests requested by the study researchers on an as-needed basis. The group of patients with symptoms of immune-related CNS damage will be asked to undergo a series of tests, including the following: * MRI procedures, with a minimum of three brain MRIs and one spinal cord MRI taken approximately 4 weeks apart * A diagnostic lumbar puncture, performed on an outpatient basis * Tests of brain and vision activity * Additional blood and tissue samples Patients with symptoms of immune-related CNS damage may be offered the opportunity to participate in additional followup tests with NIH researchers. ...

Multiple sclerosis (MS) is a chronic disease affecting the central nervous system, characterized by inflammation, demyelination, and axonal degeneration, and primarily affects young adults. Muscle weakness, sensory disturbances, spasticity, pain, visual impairment, ataxia, fatigue, cognitive dysfunction, and respiratory complications are among the most commonly reported symptoms in individuals with MS. Although inspiratory muscle training has been shown to have beneficial effects in individuals with MS, the effects of different inspiratory muscle training intensities on respiratory muscle strength and pulmonary function have not been sufficiently investigated. The primary aim of this study is to investigate the effectiveness and clinical feasibility of high-intensity interval inspiratory muscle training in individuals with MS. The secondary aim is to compare the effects of high-intensity interval inspiratory muscle training, low-intensity inspiratory muscle training, and conventional rehabilitation on respiratory muscle strength, pulmonary function, cough effectiveness, exercise capacity, lower extremity functional muscle strength, balance, fatigue, dysphagia severity, sleep quality, and quality of life in individuals with MS. Participants will be randomly assigned to one of three groups: a high-intensity interval inspiratory muscle training group, a low-intensity inspiratory muscle training group, or a conventional rehabilitation group. All three groups will receive conventional rehabilitation, while the inspiratory muscle training groups will additionally receive their respective inspiratory muscle training programs. This study aims to be the first randomized controlled trial to evaluate the effects of high-intensity interval inspiratory muscle training in individuals with MS.

Fatigue, balance impairment, and fear of falling are common problems in individuals with Multiple Sclerosis (MS). Previous studies have shown significant associations among these variables; however, the mechanisms underlying the relationship between fatigue and fear of falling remain unclear. It is possible that fatigue increases fear of falling indirectly through its negative effects on balance performance.

This project is a double-blind, sham-controlled, parallel-arm, randomized controlled trial. We will recruit n=170 people living with MS, who are experiencing an episode of depression in the context of a major depressive episode (MDE). Using our remotely supervised (RS) tDCS protocol, enrolled participants will complete 30 days of 30-minute tDCS (2.0, DLPFC left anodal) while listening to mindfulness meditation. Over the course of the study, participants will complete assessments of depression and MS symptoms. Participants will be randomized 1:1 active:sham tDCS.

The purpose of the study is to describe the safety profile of fingolimod in the Taiwanese multiple sclerosis population. This study aims to collect the safety data in patients newly initiated on fingolimod for one year.

Background: Multiple sclerosis (MS) affects the brain, spinal cord, and optic nerves. MS lesions can appear on the MRI (magnetic resonance imaging) scans in many ways. Sometimes they light up from the outer edge and fill inward. This is called ring enhancement. Researchers think this type of lesion may not heal as well as others. Corticosteroids are the standard treatment to reduce symptoms of MS relapse. But there is no standard treatment for people with enhancing MS lesions without signs of MS relapse. Researchers want to see if a short-term high-dose course of corticosteroids helps heal those lesions. Objective: To study the effects of short-term high-dose corticosteroids on ring-enhancing MS. Eligibility: Adults ages 18 and older who: * Have MS and a rim-enhancing lesion on a prior brain MRI * Are enrolled in another NINDS protocol Design: Participants will be screened under another protocol Participants will be randomly assigned to get either no treatment or 3 days of treatment with a corticosteroid. Participants will have: * 1 baseline visit * 3 days of high-dose steroids, intravenous or oral. If IV, participants will receive methylprednisolone by IV each day. Participants will also be prescribed medicine to protect their stomach. * Follow-up visits will be at week 13 and week 25 after randomization to treatment or no treatment. Visits include medical history and physical exam. Participants will have blood and urine tests. Participants will also have neurological exams and MRIs. Participants lie on a table that slides into a cylinder. They are in the scanner 1.5-2 hours. They get a dye through a catheter: A needle guides a thin plastic tube into an arm vein.

This is a randomized, open-label, parallel, Phase 3 study with 2-arms for treatment. The purpose of this study is to evaluate SC administration of frexalimab every 4 weeks (q4w) compared to IV administration of frexalimab q4w in male and female participants with RMS and nrSPMS (aged 18 to 60 years at the time of enrollment). People diagnosed with MS are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria. Study details include: The study intervention duration will be 48 weeks (12 months) for Parts A and B combined. Optional Part C will last until the initiation of a long term safety study for Frexalimab.The follow up duration after the end of study intervention (in case of discontinuation) will be 6 months. The number of scheduled visits (Parts A and B) will be 17 or 11 for participants receiving frexalimab SC or IV, respectively, with an on-site visit frequency of every month between Week 4 and Week 24 in Part A, then every 1 to 3 months in Part B, then every 6 months in Part C. Participants discontinuing treatment before the End of Study will have an additional 3 follow-up visits.

The goal of this observational cross-sectional study is to investigate the relationship between functional measures of balance and gait and objective kinetic and kinematic parameters in people with Multiple Sclerosis (MS). The main questions it aims to answer are: i) What is the relationship between kinetic and kinematic gait and balance parameters measured using the Vicon motion analysis system and performance on clinical functional assessments in people with Multiple Sclerosis? ii) Which biomechanical parameters are most strongly associated with functional balance, gait, and physical performance outcomes? Participants will attend a single laboratory-based assessment session. During this session, they will undergo biomechanical gait and balance analysis using the Vicon motion capture system, complete functional assessments of balance, gait, and physical performance, complete questionnaires assessing fear of falling and fatigue, and undergo assessment of lower-limb spasticity.

The goal of this clinical trial is to learn if a comprehensive rehabilitation programme can improve physical function, reduce fatigue, and raise quality of life in adults aged 18-65 with multiple sclerosis (MS). The study will also look at whether the programme leads to changes in brain function using magnetic resonance imaging (MRI). The main questions it aims to answer are: * Does the programme lower the overall impact of MS on daily life? * Does the programme improve walking, balance, and hand function? * Does the programme reduce the impact of fatigue? * Are there changes in brain connections after the programme? Each participant serves as their own comparison. They are tested 3 times: 2 months before the programme starts (T0), right before it starts (T1), and after 2 months of intensive treatment (T2). The period between T0 and T1, when no treatment is given, shows each person's natural changes over time. Participants will: * Attend individual physiotherapy twice a week for 2 months, then 3 follow-up sessions over the next month * Take part in 3 group movement-awareness sessions * Take part in 3 group psychotherapy sessions focused on stress management and relaxation * Receive written nutritional guidance for autoimmune conditions Tests include physical assessments, questionnaires about fatigue and quality of life, tremor measurement, and brain MRI scans. The results may help improve rehabilitation care for people with MS and support their ability to stay active in everyday and working life.

The main purpose of this study is to evaluate the safety and tolerability of the ocrelizumab subcutaneous (SC) test formulation in participants with multiple sclerosis (MS). The study consists of two treatment phases: a dose-escalation and dose-continuation phase. Participants will receive single ascending doses of ocrelizumab SC during an initial dose-escalation phase, with the option to continue treatment with the selected dose of ocrelizumab SC in the dose-continuation phase.

This study is a prospective, multi-center, randomized, double blinded, placebo-controlled study of OCR treatment-discontinuation in patients with early RMS. All eligible participants will be initiated on OCR using the standard approved administration schedule of two 300 mg infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600 mg infusions at Month 6,12, 18, and 24. At Month 24, participants will be randomized (2:1) to one of two Arms with randomized treatment beginning at Month 30: Arm 1: placebo infusions every 6 months; or Arm 2: OCR infusions every 6 months. The treatment period will be for a total of 48 months.

The primary objective of the study is to compare the prevalence rate of major congenital malformations (MCM) between 2 cohorts of pregnant participants with MS who are exposed to BRIUMVI® and who are unexposed to BRIUMVI®.

The purpose of this study is to evaluate safety, effiectiveness, and to gain insight into the treatment experience of participants prescribed BRIUMVI® (ublituximab-xiiy) in the real-world setting

Background: In people with multiple sclerosis (MS), brain and cerebrospinal fluid (CSF) biomarkers indicate inflammation or disease. Researchers want to see if 4 drugs given alone or combined affect MS biomarkers. They want to see if a change in biomarker levels can predict which drugs a person with MS might respond to. Objective: To see if signs of inflammation in CSF help predict a person s response to different drugs. Eligibility: People ages 18 and older who: * Are in protocol 09-I-0032 * Have progressive MS * Can stand and walk a few steps * Take an MS drug Design: Participants will be screened in protocol 09-I-0032. Participants will take 1 of the 4 study drugs. Researchers will call after 1 month to see how they are doing. Some will start a second drug. They may take each drug or combination for up to 18 months. Participants will have 2 visits a year for up to 6 years. Visits include: * Medical history * Physical exam * Blood and heart tests * X-rays and scans * Eye exam and tear collection * Lumbar puncture: A needle inserted between back bones removes some CSF. * Lymphocytapheresis: Blood is removed through a needle in one arm and run through a machine. The blood is returned through a needle in the other arm. * A sensor on the forehead records blood flow and oxygen use. * Participants may get a device for testing at home. Participants will stop taking the drugs if they have taken 2 drugs together for 18 months or if they do not do well on the drugs. Participants will be called 3 months later to see how they are doing.

Just-In-Time Adaptive Interventions (JITAIs) offer a framework for delivering personalized behavioral support using time-varying data to optimize the timing and type of intervention content. This project will develop the foundational components of a JITAI tailored to adults with chronic pain and either MS or SCI by drawing on symptom self-management content from existing programs (PainGuide, MyMSToolkit, and MySCIToolkit). Intervention content and delivery parameters will be refined through stakeholder engagement via structured interviews to ensure relevance, acceptability, and feasibility.