Clinical Research Directory

Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity

Reference MRI scan is recommended 6 months after treatment onset in patients with multiple sclerosis (MS), and follow-up scans at 12 months later to monitor subclinical activity. When monitoring treatment response in patients treated with disease modifying treatments (DMTs), the measurement of new or enlarging T2/FLAIR hyperintense lesions (NELs) is the preferred MRI method supplemented by contrast-enhancing lesions (CELs) for monitoring treatment response. However, some studies have suggested the deposition of gadolinium-based contrast agents in the basal ganglia and dentate nucleus of patients who underwent serial MRI acquisitions. Although significant clinical consequences of these deposits have not been demonstrated, further studies are required to better understand the potential long-term biological and clinical effects of gadolinium administration. To circumvent this potential risk, several recommendations suggested avoiding unnecessary use of gadolinium for follow-up scans. New sequences are also developed to replace gadolinium injection for the detection of active lesions. Moreover, MRI remains costly and time-consuming. In addition, systematic yearly MRI monitoring is not adapted to detect silent active lesions. This can delay identification of treatment failure and increase the risk of relapses and disability worsening, especially in the context of escalation therapy. Therefore, biological markers could allow more frequent analysis of disease activity and detect treatment failure earlier than classical clinical and MRI monitoring. Their use would greatly help clinicians to switch for high efficacy treatments (HET) and avoid potential relapses. Measurement of a structural axonal protein, neurofilament, in serum or plasma has shown promise as a marker of neuroaxonal injury and a measure of treatment response. In MS, cerebrospinal fluid (CSF) neurofilament-light chain (NfL) is also increased and is positively associated with MRI lesion load and disability scores and is a marker of treatment response. WThe study authors hypothesize that monthly plasma neurofilament-light chain (pNfL) monitoring can sensitively highlight subclinical (radiological disease activity) RDA by performing early MRI scans to confirm EDA and lead to timely treatment escalation. The main objective of this study is to compare the time to EDA in both arms (monthly pNfL monitoring vs. standard care with regular MRI scans), in patients with EDA.

Educational Programs Based on Healthy Habits to Improve Quality of Life and Psychosocial Profile in Women With Neurodegenerative Diseases: The ADVICE Protocol Study (Phase 1)

This phase of the project aims to analyze the interaction between physical exercise and the phases of the menstrual cycle, evaluating its impact on fatigue, functional capacity, and exercise perception in women with and without Multiple Sclerosis. To achieve this, a controlled, single-blind, prospective, 2x3 crossover, randomized clinical trial will be conducted, involving women with Multiple Sclerosis (MS), matched by age, lifestyle habits (smoking, physical activity), and geographic location with a group of women without MS. This study, aligned with previous findings, seeks to deepen the understanding of the role of exercise in managing Multiple Sclerosis symptoms and to promote greater adherence to personalized physical activity programs adapted to the phases of the menstrual cycle.

Exploration of Novel Imaging Biomarkers on OCT for Ublituximab Treatment Response in Multiple Sclerosis

The purpose of the research study is to explore new retinal imaging biomarkers of immune cell activity in MS during use of ublituximab (Briumvi) treatment. A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. This study will evaluate the efficacy of ublituximab to modulate MS pathology in a new manner. In order to assess this new biomarker, a specialized optical coherence tomography (OCT) scan will be performed at enrollment into the study and at 2 other timepoints throughout the study. Subjects asked to take part in this study should have been diagnosed with relapsing multiple sclerosis (MS) and have recently been advised to start the medication ublituximab (Briumvi) or are currently on another medication for the treatment of their MS. We plan to enroll 30 patients into this study. Fifteen (15) patients with Relapsing Remitting Multiple Sclerosis (RRMS) who are being initiated on B-cell depletion therapy by their treating physician at the University of Maryland Center for MS Treatment and Research will be offered enrollment into this study. Additionally, 15 age/sex matched patients with stable RRMS who are not undergoing any change in treatment and are not currently on B-cell depleting therapies will be enrolled as control subjects.

Educational Programs Based on Healthy Habits to Improve Quality of Life and Psychosocial Profile in Women With Neurodegenerative Diseases: the ADVICE Protocol Study (Phase 2)

This phase of the project aims to compare in-person, supervised educational programs (EP) with online self-guided EPs in individuals with relapsing-remitting multiple sclerosis. A total of 75 participants will be randomly assigned to one of three groups: a supervised and individualized educational program focused on HIIT training, a supervised and individualized educational program focused on strength training, and a non-supervised, self-guided educational program based on resistance band training. Additionally, sessions on the Mediterranean diet (both supervised and non-supervised) and cognitive-behavioral interventions will be included. A control evaluation will be conducted three months after the intervention to assess the effects of the educational programs, followed by another evaluation three months later to analyze residual effects. Women who participated in Phase 1 of the study will be invited to take part in this second phase.

Ublituximab (Briumvi) for Early Forms of Relapsing Multiple Sclerosis

In this prospective, open-label, single-arm, single-institution trial, the investigators will accomplish the following two aims: 1. study the safety and tolerability of Ublituximab (Briumvi) twice annually in participants with early MS over a treatment observation period of \~12 months. 2. study the pre- and post-treatment change in plasma neurofilament light chain, tested at baseline pre-Ublituximab treatment, and q24 weeks for 96 weeks post Ublituximab treatment initiation.

Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study

This pilot mixed-method study will evaluate the feasibility, preliminary efficacy, and user experience of a home-based wearable Focal Vibration Therapy (FVT) intervention for improving upper extremity (UEx) function in people with multiple sclerosis (MS). Fifteen adults with relapsing-remitting MS (PRMS) and self-reported UEx impairments will participate in a 4-week FVT program using MyovoltTM wearable FVT devices applied to arm muscles.

Effects of Ublituximab on Motor Functions in Multiple Sclerosis

The purpose of this study is to test if ublituximab changes walking functions and fall risk in people with relapsing multiple sclerosis (RMS). Twenty-five qualified people with RMS will undergo a 48-week ublituximab treatment. Before, 24 weeks into, and after the treatment, their ambulatory function, disability status, and cognition will be assessed. Additionally, they will experience large-scale slip perturbations on a treadmill under the protection of a safety harness at the last assessment. The outcome measures will be compared across the assessments to examine the effects of ublituximab on improving their walking function, disability status, cognition, and the responses to the unexpected slip perturbation.

Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)

Glucosinolates (GLs) are phytocompounds mainly found in the Cruciferae (Brassicacea) and Moringa oleifera plants. The hydrolysis of GLs by myrosinase led to the production of isothiocyanate (ITCs). ITCs consumption was associated with different health promoting effects, including to neuroprotective, anti-oxidant and anti-inflammatory capacities. In particular, they showed neuroprotective effects in experimental models of neurodegenerative diseases, including multiple sclerosis (MS) and Parkinson's disease (PD). From different GLs, different ITCs are originated. In particular, from glucoraphanin (GRA) the ITC sulforaphane (SFN) is obtained. The PI of the project is one of the proprietor of a patent (EP2908850B1) for the application of (Rs)-GRA with myrosinase in a buffered solution for the treatment of neurodegenerative diseases. The aim of this project is to evaluate the effects of the administration of bioactivated GRA in different cohorts of adult patients, affected by MS and PD, but also a cohort of pediatric patients affected by neuromuscolar and degenerative diseases. The effects of bioactivated (Rs)-GRA administration will be evaluated with a combination of clinical evaluations and a multiomic (metabolomic, genomic) approach.

Home Based Functional Balance Intervention for Multiple Sclerosis

The study involves a two-arm, Phase 1, randomized controlled clinical trial designed to establish the feasibility and effects of a Functional Balance Intervention (FBI) on physical and cognitive function, as well as measures of daily living among persons with multiple sclerosis (PwMS). Combined Specific Aims: Aim 1: Examine the effect of the FBI (Intervention Group) on physical function in PwMS compared to a stretching program (Control Group). Hypothesis 1: After four months of training, the FBI group will show significantly greater improvements in physical function compared to the stretching group. Aim 2: Examine the effect of the multicomponent FBI on cognitive function in PwMS compared to the stretching program. Hypothesis 2: After four months of training, the FBI group will show significantly greater improvements in cognitive function compared to the stretching group. Aim 3: Examine the effects of the multicomponent FBI compared to the Control Group among PwMS on measures of daily living (dual-task performance, balance confidence, community mobility, and quality of life). Hypothesis 3: After four months of training, the FBI group will show significantly greater improvements in measures of daily living compared to the stretching group. All assessment sessions will be conducted virtually via Zoom. All measures collected during the initial screening, pre-training assessment, training progression, and mid- and post-training assessment sessions will be administered either via Zoom with a Helper Buddy present or through survey links sent to participants via the UIC REDCap system. The training sessions will be performed independently by the participants in the presence of a Helper Buddy. The investigators will recruit 75 people with multiple sclerosis (PwMS) for this study. Eligible participants will be randomized to either the FBI (Intervention) or stretching (Control) group, followed by an onboarding session with a designated Helper Buddy. Training will occur twice weekly for four months. Based on the anticipated attrition rate, the investigators aim for 40 PwMS to complete the post-training assessments and finish the study.

Combined Motor Imagery and Vestibular Rehab for MS

This trial investigates the first combined use of motor imagery and vestibular rehabilitation in multiple sclerosis, aiming to evaluate their joint effect on balance, cognition, and quality of life.

Comparison of Efficacy and Safety in Patients Switching From MabThera® to Rixathon® in Relapsing-Remitting Multiple Sclerosis

This observational study investigates if switching from MabThera® to Rixathon® is associated with changes in disease activity and/or safety in people with multiple sclerosis (MS). The main questions it aims to answer are: * Does switching to Rixathon® affect tissue damage, measured by blood levels of neurofilament light (pNfL)? * Does switching to Rixathon® affect the number of new MRI lesions, relapses, or disability progression? Researchers will look at health information already collected from participants before and after the medication switch. Participants include people with MS treated at Uppsala University Hospital who switched from MabThera® to Rixathon® starting in January 2023. Researchers will use data from regular clinical visits, blood tests, brain MRI scans, and disability scores (EDSS) recorded in the Swedish MS Registry.

RESET-MS: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Multiple Sclerosis

RESET-MS: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T cells (CABA-201) in Participants with Multiple Sclerosis

"Selfie" Videos: A Novel, Patient-centered, Comprehensive Approach to Measuring Function in MS

The goal of this observational study is to validate a novel, cost-effective method for real-world assessment using patient-acquired "selfie" videos in people with multiple sclerosis. The investigators aim to prove the feasibility and validity of monitoring walking changes remotely through a truly patient-centered, low-burden, low-cost approach. The main question this study aims to answer is: do remotely collected walking and speech videos from a mobile phone match the information investigators can gather from an in person visit? Participants will collect 5 "selfie" videos at baseline, 3 months, 6 months and 12 months (about 15 minutes every 3 months). They will also come in person at baseline, 6 months, and 12 months for in person data collection (about 1 hour per in person visit).

A Study of Remibrutinib Using MR Imaging in Relapsing or Progressive MS

The study is an investigator-run, study following participants for 2 years with twice-daily remibrutinib. MRI is the main endpoint. Safety, tolerability, and efficacy are secondary endpoints. Approximately 20 participants with relapsing or progressive forms of MS will be recruited.

Sexual Dysfunction in Women With Multiple Sclerosis (MS)

Sexual dysfunction in women with multiple sclerosis (MS) is an important yet often overlooked problem. The primary objective of this study is to investigate the prevalence of sexual dysfunction in female patients diagnosed with MS. The secondary objective is to evaluate the relationship between sexual dysfunction and fatigue, depression, anxiety, overactive bladder symptoms, and cognitive dysfunction. For this purpose, the following validated instruments will be used: the Female Sexual Function Index (FSFI) to assess sexual dysfunction, the Brief International Cognitive Assessment for MS (BICAMS) to evaluate cognitive function, the Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety, the Fatigue Severity Scale (FSS) to measure fatigue, and the Overactive Bladder Questionnaire (OAB-V8) to evaluate overactive bladder symptoms.

Study to Investigate Vagus Nerve Stimulation Paired With Motor Task for Remyelination and Functional Recovery

The goal of this clinical trial is to learn if stimulating the vagus nerve in combination with a motor task in people with multiple sclerosis can improve motor function. The main questions it aims to answer are: * Is stimulating the vagus nerve safe and feasible after demyelinating episodes? * Does a paired motor task with vagus nerve stimulation improve motor function with someone who has multiple sclerosis? Researchers will compare active vagus nerve stimulation to a sham stimulation to see if the paired vagus nerve stimulation can improve motor control. Participants will: * Come in for study visits over a six month period. Study visits are three times weekly for the first month, then single follow up visits at two, three, and six months. * During study visits, participants will complete 30 minutes of the paired vagus nerve stimulation with a motor task, specifically the grooved peg test. * At various timepoints in the study, motor and disability tests will be administered to see if there are any changes in motor control for that participants. These tests include the timed 25 foot walk test, expanded disability scale, the upper extremity portion of the Fugl-Meyer Assessment, and the Multiple Sclerosis Impact Scale - 29.

Deuterium Metabolic Imaging in People with Multiple Sclerosis

The goal of this case-control study is to investigate glucose brain metabolism in people with multiple sclerosis and age- and sex-matched healthy controls. The main questions it aims to answer are: * How does brain glucose metabolism in people with multiple sclerosis compare to age- and sex-matched healthy controls? * How is the brain glucose metabolism of people with multiple sclerosis associated with disease severity? Participants will come in for testing lasting approximately three hours and undergo deuterium metabolic imaging, physical function test, cognitive function test, and answer survey.