Active clinical trials for "Multiple Sclerosis"

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and the leading cause of severe non-traumatic disability in young people, affecting 110,000 people in France. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown remarkable efficacy in Phase III trials on the inflammatory component of the disease, reducing the annualized relapse rate by 46% and the rate of new T2 lesions by 80% compared with interferon-β 1a. The use of anti-CD20 agents, including ocrelizumab, is associated with an infectious risk that increases with duration of exposure, part of which is due to the development of hypo-gammaglobulinemia in relation to cumulative dose. Several reports suggest a persistent effect of anti-CD20 drugs in MS, with no resumption of inflammatory activity after discontinuation: During the development of ocrelizumab, at the end of phase 2, after having received 3 or 4 semi-annual cycles of ocrelizumab, a safety period with a therapeutic window of 18 months was planned, before re-administration in the extension study. During this therapeutic window, the annualized relapse rate remained stable, and patients showed no radiological disease activity. Scandinavian observational studies of "off-label" use of anti-CD20 in MS provide real-life evidence of the absence of recovery of clinical and radiological activity after prolonged interruption of treatment. After 2 years of treatment, and with disease activity under control, spacing administration intervals could reduce the risk of infection without reducing treatment efficacy. This would facilitate the decision to maintain highly active immunotherapy over the long term. In addition, this therapeutic de-escalation, by reducing the frequency of infusions and associated day hospitalizations, would help to reduce treatment management costs. Our aim is to evaluate the non-inferiority of 12-monthly spacing of ocrelizumab infusions versus the conventional 6-monthly regimen, in a population of active MS patients over 18 years of age who have already received 4 or more semi-annual cycles of treatment for 2 years.

Majority of people with multiple sclerosis experience difficulty with balance and mobility, leading to an increased risk of falls. The goal of this clinical trial is to learn about brain activity during walking adaptation in people with multiple sclerosis. Also, this clinical trial will test a form of nerve stimulation to see if it can improve walking performance. The main questions it aims to answer are: What areas of the brain are the most active during walking adaptation? Can nerve stimulation make walking adaptation more effective? Participants will walk on a treadmill where each leg will go a different speed which will create walking adaptation. At the same time, brain scans will occur. There will be two sessions of walking adaptation, one with nerve stimulation, and one without nerve stimulation. Researchers will compare people with multiple sclerosis to healthy young adults to see if there are differences in brain activity.

Sphingosine 1-Phosphate (S1P) receptor modulators (S1PRMs) are part of the evolving treatment landscape of Multiple Sclerosis (MS) immunotherapies. They target the G-protein coupled S1P receptor, among other localizations expressed at the surface of lymphocytes. Binding as a functional antagonist leads to internalization of the receptor and therefore lymphocyte sequestration in the secondary lymphoid organs. The first S1PRM approved was fingolimod. More recently newer generation S1PRMs like ozanimod have been approved, which possess differences in receptor affinities, pharmacokinetics and indications (including Secondary Progressive MS or Ulcerative Colitis). Several retrospective analyses have shown that, upon cessation of fingolimod, pronounced relapse of the MS-disease called "rebound disease activity" may occur. Indeed, these relapses, sometimes with considerable severity, take place in up to 10% of patients. The risk of rebound disease of the newer generation S1PRM are not well defined. Although of utmost importance, predictive biomarkers of treatment efficacy in general and in special circumstances, e.g. an impending rebound when S1PRM cessation is planned, are scarce. In this prospective, exploratory observational study, we aim to investigate the predictive potential of the lymphocytic S1PR1 and 5 expression prior to treatment initiation with the newer generation S1PRM ozanimod on the future disease activity ("on treatment" part). Additionally, in a post-treatment part ("off treatment"), the incidence of rebound disease and the predictive potential of the lymphocytic S1PR1 and 5 expression will be examined in patients, where ozanimod has to be stopped due to clinical reasons. T and B cells from patient blood samples obtained prior to treatment start/cessation and 3 - 6 months after start/cessation will be isolated and S1PR1 and 5 staining intensity will be assessed by flow cytometry (FACS). Clinical assessments (relapse assessment, EDSS, medical history etc.) will be performed at every visit and MRI evaluation, following our standard clinical and MRI MS protocol. MRI disease activity will serve as the primary endpoint for both study groups. The relationship between the flow cytometric staining intensity and the defined endpoints will be assessed statistically by using comparative statistical approaches and multivariable regression analysis where needed for both time points. The data collected will correlate the expression pattern of S1P receptors by T and B lymphocytes to the proxy of paraclinical activity as predictive biomarkers for disease activity on treatment and after treatment discontinuation.

A Phase I First-in-Human, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate Safety, Tolerability, and Pharmacokinetics after Single Oral Dose of LPX-TI641.

Multiple Sclerosis (MS), a chronic inflammatory disease of the central nervous system, is a disease characterized by myelin, oligodendrocyte and axon damage [1]. Research continues on the autoimmune, infectious, environmental, vascular and genetic origins of this disease, which affects approximately 2.5 million people in the world and is seen 2-3 times more in women than in men. Although the signs and symptoms of the disease vary according to the location of the lesion; Loss of balance and strength, spasticity, sensory disturbances, fatigue, ataxia, autonomic dysfunction, and decreased visual acuity is frequently observed. There are no studies in the literature investigating the validity and reliability of this test in individuals with MS. Reliability is population-specific and it is important to investigate the reliability of the L test in MS patients. Therefore, the aim of our study is to reveal the test-retest reliability and validity of the L test.

The purpose of this study is to see whether using ketamine to increase glutamate in the prefrontal cortex can reduce Multiple Sclerosis (MS) related fatigue. We propose a prospective, crossover, randomized, placebo-controlled study to assess the efficacy and safety of low, single dose Ketamine, to assess its efficacy and safety in patients with MS-related fatigue.

This study aims to develop and evaluate biomarkers using non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus photography to assess the structure and function of the retinal and choroidal microvasculature and structure in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease, diseases as outlined.

CLUE is a prospective study to determine structural and functional changes of brain and spinal cord, as well as the inflammatory environment in patients with neuroinflammatory and demyelination disease. Subjects will receive new magnetic resonance (MR) technics including double inversion recovery (DIR) imaging diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM) and resting-state functional imaging and follow up for one year.

The main reason for RelevarEM project is the creation of a registry based on a web platform to facilitate the collection of epidemiological data of multiple sclerosis patients from multiple sources in Argentina. The platform will provide the data in a global way that will show the frequency and distribution of the disease in our environment at low cost.

Eye movement is a complex neurological function controlled by many structures located in the central nervous system. The eyeball is mobile within the orbit and its movements are carried out using 6 muscles innervated by 3 oculomotor nerves allowing to perform reflex or voluntary eye movements in all elementary directions. So-called internuclear structures allow the two eyeballs to perform combined movements. The attack of these structures during an acute or chronic neurological disease will most often cause oculomotor paralysis in one or more directions of gaze which will be perceived by the patient as double vision. So-called supranuclear structures make it possible to generate different types of eye movements: saccades, which are extremely rapid eye movements of very short duration, eye pursuit, which is a slow movement whose purpose is to follow a moving visual target and finally, certain neural circuits are intended to stabilize the gaze. Many neurological diseases can be accompanied by oculomotor abnormalities affecting saccades or ocular pursuit. These include neurodegenerative diseases characterized by diffuse neurological damage. Involvement of gaze stabilization structures is also frequently found in certain neurological diseases affecting the posterior fossa. The clinical examination of oculomotricity focuses mainly on the analysis of ocular mobility in the different directions of space by asking the subject to fix an object (for example a pen) or the index of the examiner in moving in different directions in space. During a classic clinical examination, it is then possible to detect anomalies such as oculomotor paralysis or nystagmus, it is however very difficult to assess the speed or the precision of the saccades, as well as the quality of the pursuit ocular. As a result, the development of techniques to accurately record eye movements has emerged as a need in order to help in the diagnosis of certain visual disorders and certain neurodegenerative diseases. Video oculography (VOG) is a technique for precisely recording and analyzing the movements of the eyeballs. The use of VOG in neurology has long been dominated by helping to diagnose certain neurodegenerative diseases and in particular certain atypical Parkinson's syndromes. The value of VOG has also been demonstrated in certain pathologies characterized by atrophy of the brainstem or cerebellum, of hereditary or acquired origin. Some studies have also assessed its contribution to the diagnosis and management of certain dementias and certain psychiatric diseases such as schizophrenia. More recently, the interest of VOG has also emerged in the management of patients with a demyelinating disease of the multiple sclerosis spectrum. The VOG has a number of limitations to its large-scale use, first of all, it is an examination requiring specific, relatively expensive equipment. On the other hand, the examination requires know-how, both for the passing of the tests but also for the processing and analysis of the data. The eVOG (mobile VideoOculoGraphy) application has been developed to record oculomotor movements during different paradigms: horizontal saccades, vertical saccades, antisaccades, horizontal pursuit, vertical pursuit thanks to a tablet fixed on a support allowing keep in a stable and fixed position. The eVOG app was compared to a conventional VOG platform in a first study. The objective was to compare the measurements obtained by the eVOG application to the measurements collected by the standard method in a sample of patients with multiple sclerosis. This study showed that the detection of different anomalies by eVOG is correlated with classic VOG. In view of these encouraging preliminary results, a prospective study could be set up with the objective of evaluating the value of digital VOG in the diagnostic process in patients referred to a tertiary center for white matter signal abnormalities on MRI. the hypothesis is that subclinical oculomotor disorders will be found more frequently in the group of patients with MS spectrum disease due to the presence in this pathology of diffuse inflammatory and degenerative damage to brain tissue, unlike the others inflammatory or non-inflammatory pathologies.