Clinical Research Directory

Effect of Corticosteroids on Inflammation at the Edge of Acute Multiple Sclerosis Plaques

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.

Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)

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.

In Vivo Characterization of Inflammation With Ferumoxytol, an Ultrasmall Superparamagnetic Iron Oxide Nanoparticle, on 7 Tesla Magnetic Resonance Imaging

Background: \- Contrast agents help things show up better on magnetic resonance imaging (MRI) scans. Researchers want to see if the drug ferumoxytol is a good contrast agent. They want to determine that it does not cause prolonged MRI changes in the brain and to see if it helps identify inflammation in multiple sclerosis Objective: \- To learn how ferumoxytol can be used to image inflammation in multiple sclerosis (MS). Eligibility: * Adults ages 18 70 who have MS. * Healthy volunteers ages 18 70. Design: * Participants will have 5 clinic visits over 6 months. * Participants will be screened with a medical history, neurological exam, and blood draw. Full clinical measures will be obtained. * Participants will have a 7 tesla brain MRI scan that may include gadolinium contrast agent. The MRI is a metal cylinder in a strong magnetic field. The participant will lie on a table that can slide in and out of the cylinder. * During visit 2, ferumoxytol with be given through a catheter (a thin plastic tube) that is inserted with a needle into a vessel in the arm. \<TAB\>- Participants will then have a 7 tesla MRI scan of the brain.. * At each of the next 3 clinic visits, participants will have a 7 tesla brain MRI and have blood drawn. The MRIs may include gadolinium. * Participants may have a full neurologic exam at these visits. At the final visit, full clinical measures will be obtained. * Participants may have more MRI scans if a 6-month MRI shows ferumoxytol still in the brain.

Identifying and Characterizing Preclinical MS

The purpose of this research study is to try and identify risk factors and biologic changes that suggest that someone may go on to develop multiple sclerosis before a person has shown any symptoms of the disease.

Emotional Processing, Family Life, Friendship and Social Integration in Patients With Multiple Sclerosis

In addition to the physical, cognitive and psychological symptoms experienced by individuals with Multiple Sclerosis (MS), there is new research which indicates that some individuals with MS have a deficit in emotional processing, specifically, facial affect recognition. Emotional processing is defined as "a central aspect of social cognition". Models of social cognition indicate that emotional processing is an essential component of interpersonal relationships. The failure to accurately perceive other's emotions has been shown to lead to difficulty in social relationships, misinterpreting other's affect, and consequently, inappropriate responding. However, even though a significant number of individuals with MS have impairments in emotional processing, we do not yet have an understanding of how these impairments affect the social functioning of individuals with MS, including the impact of these deficits on family structure. It is well-known that MS impacts one's social functioning including factors such as employment, daily living activities and interpersonal relationships. Recently a strong correlation was observed between reduced social participation in MS and quality of life. There is evidence to suggest that emotional processing deficits lie at the heart of this reduced social participation in persons with MS, leading to decreased social functioning and thus reduced quality of life. However, to date, this hypothesis has not been tested.

Intermittent Theta-Burst Stimulation for Lower-Limb Spasticity and Pain in Multiple Sclerosis

Spasticity and neuropathic pain are frequent and disabling symptoms of multiple sclerosis. Intermittent theta-burst stimulation (iTBS) is a non-invasive neuromodulation technique that may modulate cortical and corticospinal excitability and thereby improve motor symptoms and pain. This randomized, parallel-group, sham-controlled, assessor-blinded study will evaluate the clinical efficacy of active iTBS compared with sham stimulation in adults with multiple sclerosis and clinically significant lower-limb spasticity and pain. Participants will receive five stimulation sessions over one week. Spasticity, pain, patient-reported outcomes, and the electrophysiological H/M ratio will be assessed at baseline and at Weeks 2 and 4 after the intervention.

The Role of the FCRL5 Protein in the Pathophysiology of Multiple Sclerosis and Response to Treatment

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) and the leading non-traumatic cause of neurological disability in young adults. Historically considered a T-cell-mediated disease, the paradigm for MS has shifted thanks to the efficacy of therapies targeting B cells. The investigators recently identified FCRL5 as a B-cell-specific biomarker that is significantly elevated in the cerebrospinal fluid (CSF) of patients with relapsing-remitting MS and is independently associated with an increased risk of developing new MRI lesions within two years of diagnosis (ref. Deltombe et al., PMID: 41004694). This project aims to further explore FCRL5 as a prognostic biomarker, study the role of FCRL5-expressing B cells in MS pathogenesis and the effects of disease-modifying therapies on these subsets.

Development of Pain Management JITAI Content in Multiple Sclerosis and Spinal Cord Injury

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.

Cone Evasion Walk Test in Multiple Sclerosis

This cross-sectional methodological study aims to examine the test-retest reliability, intrasession reliability, and construct validity of the Cone Evasion Walk (CEW) Test in individuals diagnosed with Multiple Sclerosis (MS). The CEW test is a performance-based clinical assessment that evaluates dynamic balance, obstacle avoidance, and fall risk by quantifying the number of cones contacted during a standardized walking task. Although the psychometric properties of the CEW test have been established in populations including stroke survivors, patients with knee osteoarthritis, and patients with hip osteoarthritis, no study has yet investigated its measurement properties in individuals with MS. Given the multifaceted nature of gait and balance impairments in MS - encompassing motor, sensory, cognitive, and visuospatial deficits - the CEW test may serve as a clinically meaningful and ecologically valid tool in this population. Participants will be recruited from the Department of Neurology at Erciyes University Hospital and will undergo the CEW test along with a comprehensive battery of established mobility and balance outcome measures.

An Open-label Study of AZD0120 in Adults With Multiple Sclerosis

This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with Multiple Sclerosis.

Magnetic Resonance Imaging (MRI) to Evaluate Activity of Multiple Sclerosis (MS)

Studies performed under 89-N-0045 are designed to examine the natural history of multiple sclerosis (MS) using MRI and immunological measures. In addition to studying the natural history of untreated patients, the natural history of patients receiving approved disease-modifying therapies of MS will be examined. In both cohorts of patients levels of disease activity on MRI will be compared with immunological characteristics in order to help identify disease mechanism. Patients with either definite MS (based either on clinical or combined clinical and MRI criteria) or with an initial presentation of neurological dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI will be assessed using several MRI measures of disease activity including the number of contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to assess axonal damage. Patients will be assessed clinically and correlations between immunological and genetic factors and disease activity as seen clinically or by MRI will be studied. A second cohort of patients starting the use of approved therapy will also be examined. Patients referred to NIH prior to beginning approved therapy will be assessed with a series of three monthly MRIs to determine the level of pretreatment disease activity. After beginning approved therapy under the direction of their private physician, patients will be followed similarly to the natural history cohort. Immunological and genetic findings will be accessed before and during therapy in order to help establish the mechanisms of action of the therapies and to identify mechanisms accounting for either a response or lack of response to therapy. Part of the collected samples willl be cryopreserved to provide respository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or repsonse to therapies. Additionally, a cohort of normal volunteers will be studied. The studies in the normal volunteers will be used to establish the most appropriate imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging and to provide normative immunological measures.

Fatigue Investigation Using Digital Outcomes

This study investigates objective methods to measure and monitor fatigue in patients with post-COVID-19 condition (long COVID) and multiple sclerosis (MS), and includes a group of healthy volunteers for comparison. Fatigue is a common and debilitating symptom of both conditions, but current assessment methods rely mainly on questionnaires, which can be limited by subjectivity and recall bias. The study uses a smartphone application (the FIDO app) together with wearable devices to continuously collect data on fatigue and its fluctuations during daily life, in order to evaluate the potential of digital, objective measures compared to standard assessments. Participation lasts approximately eight weeks and includes two in-person clinic visits along with a continuous data collection phase. At the initial visit, participants complete baseline assessments and questionnaires and are introduced to the study's digital tools. During the following weeks, participants wear two wearable devices continuously (24 hours a day) and use the FIDO app to complete short daily tasks (approximately 7 minutes every two days) and brief questionnaires (approximately 5 minutes per day). All participants collect a stool sample at home at weeks 4 and 8 for gut microbiome analysis, and complete the Fatigue Scale for Motor and Cognitive Functions at week 4. At the final study visit, participants repeat a subset of the baseline assessments, provide feedback on the digital technology used, and return the study devices.

Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System

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. ...

Coupled Gentamicin-Lactobacillus Rhamnosus in NLUTD

The main objective of the proposed research study is to determine in men and women with spinal cord injury/disease and neurogenic bladder whether the dose of coupled gentamicin \& Lactobacillus rhamnosus GG affects the recolonization of the bladder, and whether the rate of success differs by sex. Secondary objectives include determining whether that recolonization lasts 7, 14, or 28 days; and safety of the coupled gentamicin \& Lactobacillus instillations.

A Study Evaluating the Effect of BRIUMVI® (Ublituximab) on Pregnancy and Infant Outcomes in Participants With Multiple Sclerosis (MS)

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®.

A Study to Evaluate Pharmacokinetics (PK) and Safety of Subcutaneous (SC) Ublituximab Administered at Various Injection Sites and Relative Bioavailability Via Autoinjector (AI) Versus Syringe Subcutaneously in Participants With Multiple Sclerosis (MS)

The purpose of this study is to evaluate the PK and safety of ublituximab SC at different sites of administration and relative bioavailability of ublituximab SC administered with a prefilled pen versus syringe.

Brain and Behavioral Influences on Motor Skill Learning in Multiple Sclerosis

Multiple Sclerosis (MS) is characterized by episodic attacks in which there are sharp declines in physical function. Although neurorehabilitation is the most promising clinical strategy for motor recovery in patients with MS, treatment responsiveness and outcomes are mixed. This is perhaps because each individual with MS has a different capacity to improve with rehabilitation, and this capacity may be based on a variety of baseline factors, such as disease duration, motivation, cognitive status and integrity of underlying brain structures. A better understanding of what "key ingredients" facilitate relearning of motor skills during neurorehabilitation is critically needed. Much of the focus of rehabilitation is on relearning motor skills. The initial stage of learning a motor skills often requires explicit concentration on the details of the movement. As one becomes more proficient in the motor skill, it becomes less attention-demanding and more automatic. Those who can perform motor skills more automatically will be better able to manage the additional demands of a secondary task; thus, capacity for dual-task performance can be used as an index of automaticity. Individuals with MS experience demyelination that impacts brain areas critical for motor learning. However, the specific clinical and pathological variables that facilitate capacity for motor learning in people with MS have not been identified. Identification of such variables could be leveraged to determine a patient's capacity to benefit from neurorehabilitation at the outset and potentially to maximize motor learning during rehabilitation for people with MS. Thus, there is an urgent need to determine the key ingredients most strongly associated with successful relearning of motor skills in MS patients. Our long-term goal is to develop individualized rehabilitation for persons with MS. Our overall objective in this application is to identify clinical and pathological variables associated with successful relearning of motor skills. Our central hypothesis, based on preliminary data, is that the ability to learn to make new movements automatically occurs over a dynamic range and is a function of available cognitive processing speed and the integrity of corticospinal tract and superior cerebellar peduncles. We will test these hypotheses by recruiting 146 individuals with relapsing-remitting MS to participate in a mechanistic trial not designed to be a therapeutic intervention. Participants will complete baseline testing (including neuroimaging, cognitive testing and dual-task performance) followed by 4 consecutive days of training on a challenging balance task. After a 2-day washout period, participants will return for post-testing (including dual-task performance on a dual-balance and working memory task). The rationale for the proposed research is that identification of key ingredients associated with the capacity for motor skill acquisition would allow for more targeted rehabilitation programming, thereby improving patient outcomes and reducing health care expenses. At the completion of the proposed research, we expect to understand more about the capacity for individuals with MS to improve with motor skill training, and some of the key ingredients that help predict successful shift toward task automaticity, one critical component of successful neurorehabilitation. The results of this proposal will facilitate the development of predictors of motor recovery, needed to improve rehabilitation outcomes for individuals with MS and other neurodegenerative diseases.

TRAIN-BW: Backward Walking Training in Multiple Sclerosis

Individuals with multiple sclerosis (MS) experience in impairments in mobility and cognition that increase the risk for accidental falls. More than 50% of individuals with MS experience injurious falls within a 6-month period. Current interventions to improve fall risk have focused on forward walking (FW) and balance training, resulting in small declines in the relative risk for falls with a large degree of variability. Interestingly, motor differences between MS and healthy controls are more pronounced in backward walking (BW), yet no studies have investigated BW training as an intervention to reduce fall risk in persons with MS. This study will investigate the feasibility, acceptability and impact of BW training compared to forward walking training on motor function and fall risk in persons with MS.

Pain Phenotypes in Individuals With Multiple Sclerosis

This observational cross-sectional study aims to determine chronic pain phenotypes in individuals with multiple sclerosis (MS) and to investigate the clinical characteristics associated with different pain phenotypes. Participants with MS and chronic pain will undergo a comprehensive clinical assessment to identify nociceptive, neuropathic, nociplastic, and mixed pain phenotypes. The assessment will include clinical history, pain characteristics and distribution, quantitative sensory testing, pain intensity, disease severity, fatigue, health-related quality of life, and pain catastrophizing. The clinical characteristics of participants with different pain phenotypes will subsequently be compared.

PLasmatic Extracellular Vesicles AS Biomarkers of nEural Tissue Damage

Recently proposed central nervous system damage biomarkers detectable in biofluids, such as neurofilament light chain (NfL) have several limits, including a lack in specificity and a kinetic that does not allow them to be used as outcome measures in clinical trials for neurodegenerative diseases such as the progressive forms of multiple sclerosis (MS) or the sequelae of stroke. Our team has pioneered the detection of central nervous system (CNS) extracellular vesicles (EVs) as biomarkers in MS and Alzheimer's Disease. If EVs are not the best solution themselves, we propose also to investigate their content to reveal potential new biomarkers having the same significance and an easier detection technology. Thus, we propose here to set-up front line technologies to detect EVs of CNS origin, or their content, in the plasma of persons affected by MS or by stroke to find better ways to monitor ongoing neurodegenerative processes and therefore allow easier development of new treatments.

Motor Imagery and Action Observation for Gait Function in MS

This study will investigate whether mentally simulating walking movements while watching others walk can improve walking performance in individuals with Multiple Sclerosis (MS). Participants will be divided into two groups: one group will watch walking videos and imagine themselves walking, while the other group will watch nature scenes. The study will measure muscle activity and walking patterns to assess the effects. The results may help support the use of mental practice techniques to improve mobility in people with MS.

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis

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 for participants receiving frexalimab SC or IV, 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.

Evaluating the Use of Oral Indapamide to Reduce Disabiltiy Progression in Progressive Multiple Sclerosis (MS)

The goal of this clinical trial is to determine whether treatment with indapamide can slow the rate of progression in patients with progressive forms of multiple sclerosis (MS). The main question it aims to answer is whether this treatment can reduce the speed at which the walking speed of patients with progressive MS (PMS) worsens. Participants will take an indapamide tablet once daily for 12 months. During this time, among others, their walking speed will be assessed several times.

A Study Evaluating the Safety and Efficacy of KITE-363 in Relapsed/Refractory Autoimmune Neurologic Diseases

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.