Clinical Research Directory

MS-Related Disability Worsening and Thalamic Volume Loss

PENTAGON is an observational, non-interventional, multicenter, prospective cohort study conducted at approximately 20 neurology centers and affiliated radiology centers across Germany. It investigates whether loss of thalamic volume (TVL) is an independent driver of disability progression in patients with relapsing-remitting multiple sclerosis (MS). The study observes two groups: patients with active MS (receiving or about to receive first- or second-line disease-modifying therapies) and patients with progressive MS. Over a 24-month primary observation period - extendable to 72 months - MS-related disability is measured with the Expanded Disability Status Scale (EDSS), and whole-brain and thalamic volumes are quantified from standardized high-resolution T1-weighted MRI using validated deep-learning methods. The primary objective is to demonstrate that the change in MS-related disability over 24 months is inversely associated with the change in thalamic volume over the same period. No procedures beyond routine clinical care are required.

Treatment of Cognitive Deficits in Multiple Sclerosis With High-Definition Transcranial Direct Current Stimulation

The purpose of the study is to test whether low level electric stimulation, called transcranial Direct Current Stimulation (tDCS), on the part of the brain (i.e., presupplementary motor area) thought to aid in memory will improve verbal retrieval in multiple sclerosis patients. The primary outcome measures are neuropsychological assessments of verbal retrieval, and the secondary measures are neuropsychological assessments of other cognitive abilities and electroencephalography (EEG) measures. Additionally, the study will examine the degree to which baseline assessments of cognition and concussion history predict responses to treatment over time, both on assessments administered within the intervention period and at follow-up.

Examining Effects of Ocrevus on Cognitive Fatigue Using fMRI

The purpose of this research study is to investigate the effectiveness of MS Disease modifying medications on cognitive fatigue in persons with relapsing remitting multiple sclerosis (RRMS). Cognitive fatigue is the kind of fatigue that occurs after intense mental concentration as after a session of problem solving.

Examining Effects of Tysabri on Cognitive Fatigue Using fMRI

The purpose of this research study is to investigate the effectiveness of Tysabri on cognitive fatigue in persons with Relapsing-Remitting Multiple Sclerosis (RRMS). Cognitive fatigue is the kind of fatigue that occurs after intense mental concentration as after a session of problem solving.

Cognitive Disability and Quality of Life of Patients Suffering From Multiple Sclerosis and Treatment With Immunosuppressant

Multiple Sclerosis is the first cause of neurological handicap in France. The importance of cognitive disabilities, their evaluation and their impact on patients' life have only been comprehended recently. Immunosuppressants represent new treatments in Multiple Sclerosis (MS) but imply a lot of constraints. This study will evaluate the impact of these treatments on cognitive disabilities, tiredness state, emotion and quality of life in general, on a lengthened period.

Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial

FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The infectious risks and other complications associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability. The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic, randomized controlled trial that has two primary aims: 1) to evaluate, jointly and independently among patients deemed at higher risk vs. lower risk for disability accumulation, whether an "early aggressive" therapy approach, versus starting with a traditional, first-line therapy, influences the intermediate-term risk of disability, and 2) to evaluate if, among patients deemed at lower risk for disability who start on first-line MS therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.

A Study to Asses Efficacy, Safety and Tolerability of Monthly Long-acting IM Injection of GA Depot in Subjects With RMS

A multinational, multicenter, randomized, Phase III, double blind, parallel group, placebo controlled study in subjects with Relapsing Forms of Multiple Sclerosis (RMS) to assess the efficacy, safety and tolerability of GA Depot, a long acting IM injection of glatiramer acetate, administered once every four weeks

Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis

The purpose of this study is to better understand the mechanism of action (MoA) of cladribine tablets by exploring the effect on central nervous system (CNS) and blood biomarkers relevant in the relapsing forms of multiple sclerosis (RMS; to include relapsing-remitting MS \[RRMS\] or active secondary progressive MS).

Effects of Chiropractic Care on Cytokine Levels in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory autoimmune disease associated with an imbalance between pro- and anti-inflammatory markers (cytokines) resulting in a demyelinating and neurodegenerative disease. There is early evidence that spinal manipulation (chiropractic care) is better than control in influencing immune (cytokine) activity in asymptomatic participants, but few studies have been completed in participants with chronic inflammatory conditions, such as MS. The purpose of this project is to examine the immediate (after a single thoracic spinal manipulation treatment) and summative impact (after 8 thoracic spinal manipulation treatments occurring over 4 weeks) on pro-inflammatory (interleukin (IL) IL-1ß, IL-2, IL-6, Tumor necrosis factor-alpha) and anti-inflammatory (IL-4, IL-10) plasma cytokines 20 minutes and 2 hours after thoracic spinal manipulation in participants diagnosed with neuroinflammatory relapsing-remitting MS (RR-MS). Spinal manipulation treatment will be limited to the thoracic spine. Secondary outcomes will include determining the impact of 8 thoracic spinal manipulations on fatigue, cognitive processing speed, pain, depression, sleep, and motor function through questionnaires and performance of various in assessments such as the timed 25 foot walk test.

Assessing Changes in Multi-parametric MRI in MS Patients Taking Clemastine Fumarate as a Myelin Repair Therapy

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with chronic inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments. No reparative therapies exist for the treatment of multiple sclerosis. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at the University of California, San Francisco (UCSF). Following in vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of multiple sclerosis in the context of chronic optic neuropathy. That pilot study was recently completed and is the first randomized control trial documenting efficacy for a putative remyelinating agent for the treatment of MS. The preselected primary efficacy endpoint (visual evoked potential) was met and a strong trend to benefit was seen for the principal secondary endpoint assessing function (low contrast visual acuity). That trial number was 13-11577. This study seeks to follow up on that study and examine clemastine fumarate's protective and reparative effects in the context of chronic demyelinating brain lesions as imaged by multi-parametric MRI assessments. The investigators will be assessing the effects of clemastine fumarate as a remyelinating therapy and assessing its effect on MRI metrics of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis. In addition to using conventional multi-parametric MRI assessments, this study will also evaluate a new MRI technique called Ultrashort Echo Time (UTE) MRI to assess the effects of clemastine fumarate as a remyelinating therapy of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis and compare it to the other assessments.

B Cell Tailored Ocrelizumab Versus Standard Ocrelizumab in Relapsing Remitting Multiple Sclerosis

Rationale: B-cell depleting therapies like ocrelizumab are very effective in the treatment of relapsing remitting multiple sclerosis (RRMS). As B cell repopulation varies extensively between individuals (ranging from 27-175 weeks), using a treatment scheme with a fixed infusion interval may be suboptimal. So far personalized adapted treatment of ocrelizumab in RRMS has not been studied in a prospective setting. Objective: Evaluating the efficacy, safety and cost-effectiveness of ocrelizumab when administered in personalized B cell tailored intervals in RRMS patients. Study design: This is a national multicenter randomized controlled trial with 96 week follow-up. Study population: The study population consists of 296 adult RRMS patients who have received ocrelizumab treatment for a minimum of 12 months (2x 300 mg infusion and 1x 600mg infusion). Intervention: Patients will be randomized into the standard interval group (600 mg infusions every 24 weeks) or the personalized interval group in which the infusions will be extended as long as the serum CD19 B cell count is below 10 CD19 cells/µL, determined every 4 weeks. Main study parameters: To conclude non-inferiority of personalized B cell tailored ocrelizumab there will be two co-primary endpoints: 1. the difference of percentage of confirmed relapse-free patients between the two groups after 96 weeks and 2. the difference of percentage of patients free from new/enlarging T2 lesions on MRI between the two groups after 96 weeks. Secondary study parameters are number of confirmed relapses, annualized relapse rate, number of new T2 lesions and brain atrophy on MRI, disability progression, no evidence of disease activity (NEDA), MS disease biomarkers (serum neurofilament light), quality of life, burden of treatment, immunoglobulin levels and (serious) adverse events including occurrence of infections and COVID-19. Furthermore, various immune cell subsets will be studied in relation to ocrelizumab concentration in a subgroup. Nature and extent of the burden and risks: All patients will be subjected to visits every 24 weeks including clinical scoring and questionnaires. Blood samples and MRI scans will be taken and performed every 48 weeks. Continuous assessment of key stroke dynamics on the patients smartphone and monthly digital cognitive test and walk test will be performed in most patients. As CD19 B cells are kept near complete depletion, the estimated risk of recurrence of disease activity is very low.

Safety and Efficacy of Extracorporeal Photopheresis (ECP) in the Treatment of Multiple Sclerosis

PHOMS Study is a randomized, controlled, open-label, prospective, and multicentric clinical trial involving outpatients diagnosed with Secondary Progressive Multiple Sclerosis (SPMS) or Relapsing-Remitting Multiple Sclerosis (RRMS). The primary objective is the safety profile assessment of the investigational intervention (Extracorporeal Photopheresis -ECP) and its preliminary efficacy evaluation, while the secondary objective is the assessment of the immune response profile in MS patients.

Study to Evaluate the Effectiveness and Safety of Ozanimod Compared to Fingolimod in Children and Adolescents With Relapsing Remitting Multiple Sclerosis

The purpose of this study is to evaluate the effectiveness, safety, tolerability, drug levels and drug effects of ozanimod compared to fingolimod in children and adolescents with relapsing remitting multiple sclerosis (RRMS).

ITAKOS - Italian Observation, Multicenter, Prospective Study of Ofatumumab in RRMS Patients

Study to evaluate the effectiveness of ofatumumab in Italian RRMS patients in the real-life setting.

Effects of Ocrelizumab Treatment on Immune Cells in Lymph Nodes in Multiple Sclerosis

B cell-depleting therapies, such as ocrelizumab, are among the most effective medications currently available for the treatment of multiple sclerosis (MS). This suggests that B cells play a very important role in MS. While B cells are rapidly eliminated from the blood of patients treated with medications like ocrelizumab, little is known about how effectively B cells are eliminated from lymph nodes, which are important sites of B cell activation. This study is being conducted to determine to what extent B cells are targeted in lymph nodes following ocrelizumab treatment, which may have important consequences for long-term MS outcomes.

Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS

This study seeks to explore changes in the neural pathways and arm function following a breathing intervention in the multiple sclerosis (MS) population. The breathing intervention, known as Acute Intermittent Hypoxia (AIH), involves breathing brief bouts of low levels of oxygen. Research has found AIH to be a safe and effective intervention resulting in increased ankle strength in people with MS. Here, the study examines arm and hand function before and after AIH. In order to better understand the brain and spinal cord response to AIH, the investigators will measure muscle response, and signals sent from the brain to the arm muscles before and after AIH.

Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis

Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 versus Placebo in Adults with Relapsing Multiple Sclerosis (ENSURE-2)

The Synergistic Effects of AIH and FES in Persons With MS

The purpose of this study is to examine how neuromuscular electrical stimulation (NMES), may synergistically enhance corticospinal excitability in people with relapsing form multiple sclerosis (MS). This is an important intermediate step to evaluate the potential of AIH + NMES as a plasticity-priming strategy for more efficacious interventions for persons with MS. This study will measure ankle torque generation and amplitude of motor evoked potentials (MEPs) using a repeated measures study design in order to better understand the effects of AIH combined with NMES, as compared to only receiving NMES, and only receiving AIH.

Fatigue Alleviation Through Neuromodulating Therapy in Multiple Sclerosis

The goal of this clinical trial is to learn if repetitive Transcranial Magnetic Stimulation (rTMS) of the left premotor cortex can lessen fatigue in patients with Multiple Sclerosis, and if this is a feasible intervention. It will also give further information on fatigue in Multiple Sclerosis. The main questions it aims to answer is: * Does premotor rTMS decrease fatigue symptoms in patients with Multiple Sclerosis? * Is the change in fatigue reflected in an altered balance between brain excitation and inhibition in the targeted premotor cortex? Researchers will compare real rTMS with sham rTMS (which does not stimulate with a magnetic field), to see if real rTMS works to alleviate fatigue. Participants will: * Receive real or sham rTMS for 30 minutes, 5 days in a row * Visit the clinic before and 6 days after for baseline and follow-up * Fill out on-line questionnaires 1 day and 4 weeks after the end of intervention * Undergo a total of 3 brain scans (Magnetic Resonance Imaging at ultra-high field), at baseline, end of intervention, and follow-up * Undergo lab neurophysiological measurements before and after the first intervention session * Keep a fatigue diary and wear an activity tracker in the period before and after the intervention

Clinnova-MS: A Prospective Cohort Study of Patients With Multiple Sclerosis: A Trans-regional Digital Health Effort Unlocking the Potential of Artificial Intelligence and Data Science in Health Care

The Clinnova-Multiple Sclerosis (MS) study is part of the Clinnova program (NCT06526364; NCT06235684 and NCT05733702), which seeks to advance precision medicine and the digitalization of healthcare through high-quality, interoperable health data. This program focuses on people with multiple sclerosis (MS) and aims to identify objective surrogate markers derived from clinical, epidemiological, imaging, and omics data that can predict disease activity, such as progression or relapses. By combining data science and artificial intelligence, the project seeks to improve patient stratification, support personalized therapeutic decisions, and provide insights into the mechanisms underlying treatment response and disease progression. Although many therapies are available for MS, it remains challenging to determine the most appropriate strategy for each patient and to prevent long-term disability. Current treatments mainly target relapses and inflammation, with limited effects on chronic progression. Clinnova-MS will collect and analyze real-world and research data to better understand variability in disease activity and treatment outcomes, enabling more precise, evidence-based care within the standard of care. This study represents the first step toward the broader Clinnova objective: developing sustainable, personalized, and preventive healthcare for people living with MS.

Clinnova-MS: A Prospective Cohort Study of Patients With Multiple Sclerosis (Switzerland)

This prospective cohort study is part of the Clinnova programme and aims to (i) identify clinical imaging and omics characteristics associated with early Multiple Sclerosis (MS) and with transitioning phases to progressive MS, as well as (ii) to investigate digital biomarkers allowing the continuous clinical monitoring of those patients.

Behavioral Intervention for Physical Activity and Sexual Dysfunction in Multiple Sclerosis

The prevalence of sexual dysfunction is higher among women with multiple sclerosis (MS) than women in the general population. The presence of sexual dysfunction is associated with decreased well-being and quality of life. There is limited research supporting pharmacological and other therapeutic approaches for managing sexual dysfunction in MS. Physical activity has beneficial effects on many of the consequences of MS, and physical activity represents a promising non-pharmacological approach for managing symptoms of sexual dysfunction in MS. The proposed research examines the effect of an Internet-delivered lifestyle physical activity intervention for improving sexual dysfunction in women with MS. The research proposed, if successful, will provide evidence for the efficacy of physical activity as a translatable approach for managing sexual dysfunction among women with MS.

Impact of the Cionic Neural Sleeve on Mobility in Multiple Sclerosis

The purpose of this research is to support the clinical value of the Cionic Neural Sleeve for individuals diagnosed with multiple sclerosis (MS).

Efficacy of Diet on Quality of Life in Multiple Sclerosis

The overarching goal of this project is to critically evaluate the efficacy of incorporating dietary guidance within multiple sclerosis (MS) care for improving long-term quality of life (QoL) compared to usual care. The primary objective of this study is to evaluate the effect of two dietary interventions (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination) on MS QoL compared to usual care control (Dietary Guidelines for America), and the secondary objectives and the long-term effects on, motor function, low-contrast vision sensitivity, fatigue, mood, and disease activity assessed by brain imaging.