Active clinical trials for "Sclerosis"

Amyotrophic lateral sclerosis (ALS), is a rapidly progressive neurodegenerative disorder, usually leading to death from respiratory failure in 3-5 years. Riluzole, the only drug currently available, only modestly prolongs survival and does not improve muscle strength or function. In ALS, loss of functional motor neurons is initially compensated for by collateral reinnervation and strength is preserved. In the majority of ALS patients, as the disease progresses, compensation fails leading to progressive muscle weakness. Conversely, in long-term ALS survivors, slow functional decline is correlated with their ability to maintain a successful compensatory response to denervation over time. Compensatory collateral reinnervation is thus essential for functional motor preservation and survival, and elucidation of the molecular mechanisms involved is crucial to help identify new therapeutic targets. Energy metabolism and glucose homeostasis modifications also influence disease clinical course but the mechanisms by which they contribute to the progression of ALS are unknown. Weight loss is an independent negative prognostic factor for survival and, by contrast, ALS risk and progression are decreased in individuals with high body mass index and non-insulin-dependent diabetes mellitus. Insulin shares many common steps in its signaling pathways with insulin-like growth factor 1 (IGF-1), and is thus at the interface between glucose homeostasis regulation and maintenance of muscle mass. However, the contribution of insulin signaling to preservation of muscle innervation and function in ALS has never been investigated. With this study, we aim to determine the role of insulin signaling pathways in maintenance of collateral reinnervation and muscle function in ALS. We will also investigate the link with the disease-modifying effect of metabolic and glucose homeostasis perturbations, by identifying the contribution of metabolic profiles to preservation of skeletal muscle innervation and motor function in patients with ALS. For this purpose, we will determine the whole-body and skeletal muscle metabolic profiles of 20 patients with ALS and correlate these results to collateral reinnervation ability quantified on muscle biopsy specimens. For each patient, we will use both clinical and electrophysiological methods to evaluate motor function and motor neuron loss over time. Body composition, insulin secretion, insulin resistance level and serum concentrations of IGF-1 axis components will be determined. A motor point muscle biopsy will be performed for morphological analysis of neuromuscular junctions and quantification of innervation by confocal microscopy. Activation of insulin/IGF-1 canonical signaling pathways and metabolic pathways of glucose homeostasis will be quantified in muscle specimens. Skeletal muscle and whole-body metabolic parameters will be analyzed together and correlated with clinical assessment of motor function, electrophysiological data, and innervation quantification results. For comparison, 10 healthy subjects of similar age and 10 patients with spinal and bulbar muscular atrophy - a slowly progressive motor neuron disorder with maintenance of effective collateral reinnervation - will be used as controls. This study will be the first to address the question of the contribution of insulin signaling pathways and metabolic profiles in maintenance of muscle reinnervation and function in ALS patients. The molecular mechanisms identified will be new targets for future treatments promoting compensatory reinnervation and slowing disease progression in ALS. Ultimately, this translational project could have a significant therapeutic impact in disorders with muscle denervation and collateral reinnervation as a compensatory mechanism, such as spinal muscle atrophy or peripheral neuropathies.

In multiple sclerosis (MS), the sequence of events leading to irreversible neuro-axonal degeneration, which is a major determinant of clinical disability, is poorly understood. Recently, the key role of neuronal energy dysfunction in driving axonal degeneration has been highlighted. In the neuronal injury pathway triggered by inflammation and myelin disruption, multiple adaptive changes force the neuron to a temporary condition of "virtual hypoxia", characterized by a mismatch between energy demand and supply. If this condition of energy dysregulation is not reversed within an appropriate time-window, neurons enter an irreversible axonal degeneration. Two key questions on the relationship between early energy dysregulation and neurodegeneration remain unanswered: i) whether brain energy dysfunction measured at a given time point can predict the subsequent occurrence of neurodegeneration; ii) to what extent and for how long neurons can bear this "virtual hypoxia" before undergoing structural damage. Tracking the "energetic signature" of MS and defining its temporal distance from irreversible damage is essential for the development of neuroprotective therapies.The recent optimization of innovative magnetic resonance (MR)-based techniques such as sodium (23Na) MRI, phosphorus MR spectroscopy (31P-MRS), and diffusion-weighted 1H MRS (DW-MRS) has allowed the generation of promising in vivo data on cellular energy dysregulation in MS. The main objective of this project is to explore whether MR-derived metrics of energy dysregulation predict MR-derived parameters of cortical neurodegeneration developing over 2 years, as reflected by cortical atrophy. To address this key question, the Investigators will use a combination of 23Na MRI, 31P MRS, and DW-MRS associated with advanced MRI sequences to explore energy dysregulation in the sensorimotor region, and measurements of cortical atrophy in the same area after 24 months in 40 patients with either relapsing-remitting or progressive MS and 15 age- and gender-matched healthy controls. The Investigators will also test whether MR-derived metrics of energy dysregulation at study entry correlate, both cross-sectionally and longitudinally, with: i) global cortical atrophy; ii) functional cortical reorganization resulting from the condition of energy dysregulation, which precedes the occurrence of structural damage; iii) cortical demyelination and remyelination; iv) clinical, neuropsychological and biological measures.

The goal of this pilot study is to assess the feasibility of a larger study on the efficacy of mycophenolate mofetil in people diagnosed with systemic sclerosis with mild lung involvement. Participants will be recruited over 12 months at 3 academic centers and assigned randomly to receive either mycophenolate mofetil or placebo, a look-alike substance that contains no active drug, for 96 weeks.

This is a placebo-controlled, double-blinded, randomized trial design, whereby all patients are eligible to start an injectable therapy, and then randomized to either placebo or FMT for approximately 1 year.

Multiple sclerosis (MS) in children, a rare disease, follows a relapsing remitting course with a shorter interval between the first 2 clinical events and higher annualized relapse rate as compared with MS in adults. Residual deficits following clinical events are less frequent. The vast majority of children and adolescents with MS are thought to have a greater potential for myelin repair than adults. However convincing data in the literature to support this hypothesis are lacking, because until now no imaging technique has been validated to measure remyelination in vivo.

The goals of this observational study are to evaluate (1) the feasibility, usability, and satisfaction with the Cubii elliptical and (2) the preliminary efficacy of the Cubii elliptical for increasing activity (primary outcome), physical function, and quality of life, and decreasing physical and psychological symptom (e.g., pain, fatigue, depression) severity in people with MS. The main question it aims to answer is how usable and feasible is the Cubii as a mode of exercise for people with MS? Participants will use the Cubii as they choose and keep a written log of this use. They will answer questions about their demographics, MS disease-related variables (e.g., pain, fatigue, falls), activity, exercise, quality of life, and biopsychosocial symptom variables) and provide additional data regarding the feasibility, usability, and satisfaction with use of the Cubii.

Multiple Sclerosis (MS), causing damage to myelin sheath and axons; It is a chronic disease with diffuse demyelinating lesion of the Central Nervous System (CNS) that often affects young adults, progresses with attacks and remissions, and may bring about functional limitation, disability or decrease in quality of life. The fact that Multiple Sclerosis is chronic and irreversible, the uncertainty and destructiveness of the disease process affect individuals physically over time, but it can also cause many negative symptoms from a mental perspective. Studies have shown that MS disease; anxiety, depression, loss of life purpose, intense hopelessness and suicide. Life purpose has been defined as struggling to achieve one's goals and creating meaning against existential neurosis. Having a life purpose increases the subjective well-being, life satisfaction and hope level of individuals. According to the Turkish Language Association, hope, which is defined as "the feeling of trust arising from hope" and which indicates the feeling of having positive expectations for the future, positively affects mental health by giving people the feeling that they can cope with negative experiences that they may encounter in the future. Hopelessness, which is the opposite of hope, is a feeling that causes mental problems such as depression and suicide as well as negatively affecting the mental health of the individual and is a part of these clinical pictures. Setting a life purpose has positive effects on hope. While a purposeful life increases the level of hope in people, it reduces hopelessness and causes the person to live a more meaningful life. The decrease or loss of hope and the purpose of life can cause significant problems for people such as depression, addiction or suicide may occur in people who have lost their life purpose and hope. Positive psychotherapy (PPT), one of the psychosocial-based intervention methods, is a therapy method with a humanistic approach, the theoretical foundations of which were established by Pesesschkian in 1970. There are three basic principles of therapy: hope, balance and consultation. In Positive Psychotherapy, the symptoms and ailments in the person; It is positively reinterpreted, emphasizing real talents. Sharing the function of the existing symptom with the client increases the client's acceptance and hope for himself and his situation, which in turn activates the hope principle.

Mesenchymal stromal cells (MSC) are multipotent cells which carry immunomodulatory, pro-angiogenic and anti-fibrotic properties, that can target Systemic Sclerosis (SSc) pathogenesis and its clinical manifestations. The increasing use of MSC, harvested from bone marrow (MSC(M)), adipose tissue (MSC(AT)), or umbilical cord (MSC(UC)) in a variety of indications, provides consistent evidence supporting their safety in humans. The efficacy of MSC(M) intravenous (IV) injection for treating acute graft versus host disease led to their marketing approval in 2012 and MSC(AT) (Alofisel) were approved for severe Crohn's fistula in 2018. MSC represent a promising therapeutic approach for SSc. We previously a) showed disease-specific abnormalities in MSC(M) from SSc patients, providing strong rationale to use allogeneic MSC to treat SSc patients, b) completed the first phase I/II dose escalation trial using allogenic MSC(M) infusion in 20 severe SSc patients (ClinicalTrials.gov: NCT02213705, PHRC AOM 11-250) with no safety issues, significant improvement in skin fibrosis at 3 to 6 months after infusion which appeared lower thereafter, thereby supporting the need for repeated infusions. In vitro, experimental and clinical studies suggest that MSC properties vary according to their tissue of origin/source. We demonstrated that compared to MSC(M), MSC(AT) are easier to harvest and display higher proliferative capability before entering senescence, higher genetic stability, and superior immunosuppressive properties. The objective of the present research is the successful production of allogeneic MSC(AT) derived from selected healthy donors, with adequate phenotypic criteria according to the International Society for Cell & Gene Therapy. Considering the above rationale, these MSC(AT) will subsequently be used in a Phase I/II randomized clinical trial testing allogeneic MSC(AT) systemic infusion for treatment of severe systemic sclerosis.

The goal of this clinical investigation is to evaluate the effectiveness of home use of a lightweight robotic lower limb exoskeleton as a walking aid device on quality of life in patients with multiple sclerosis with gait disorders. Participants will wear an exoskeleton (Keeogo) for 8 weeks at home during the experimental phase. This phase is compared to an 8-week control phase at home with advice on regular physical activity adapted to their abilities.

TITLE: Exergaming with Immersive Virtual Reality for people with Multiple Sclerosis INTRO: Multiple Sclerosis (MS) is an autoimmune and chronic neurodegenerative pathology caused by loss of the myelin sheath in the nervous system, causing motor, cognitive, behavioral and sensory symptoms. Conventional physiotherapy often includes exercise therapies, based on repetitive performances that can sometimes be unmotivating for patients. Immersive Virtual Reality could offer programs based on exercise (exergames) that are motivating, as well as appropriate to the therapeutic objectives of the target group. This tool has already been successfully tested in other groups (post stroke, Parkinson's,...) with promising results. Our ExeRVIEM project (Exergaming with Immersive Virtual Reality in Multiple Sclerosis) represents a new strategy to improve functionality in people with MS, using an exercise program with Virtual Reality glasses. HYPOTHESIS: The practice of the ExeRVIEM protocol based on physical function training in people with MS contributes to the maintenance and improvement of functional capacities, reducing the number of falls and increasing their personal autonomy. GENERAL OBJECTIVES: 1.1 Design and implement an ExeRVIEM exercise program/protocol to improve balance in older people 1.2 Analyze the effects of this ExeRVIEM program/protocol, in the short and medium term in people who attend an Association of patients. 1.3 Identify if there is a relationship between the variables that induce frailty and functional dependence and the ExeRVIEM protocol. SPECIFIC OBJECTIVES: 2.1 Determine and apply the ExeRVIEM protocol to explore differential effects for 6 minutes a day (2 days a week for 8 weeks). 2.1.1 Improving the functional independence and mobility of people by improving balance, reducing the risk of falls and the correct development of activities of daily living. 2.1.2 Gait improvement. 2.1.3 Improved functionality. 2.1.4 Improving grip strength. 2.1.5 Improving reaction times. 2.1.6 Improving the perception of fatigue 2.2 Determine the influence of parameters related to exposure to RVI. 2.2.1 Safety of the virtual reality exhibition 2.2.2 Usability of the virtual reality exhibition 2.2.3 Personal experiences and satisfaction of the virtual reality exhibition METHODS: Design: Randomized controlled trial. People diagnosed with MS who attend the AVEMPO VIGO center in Spain on a regular basis will be invited to participate in the study. After they meet the selection criteria, they will be assigned to an experimental group and a control group. Information on the sociodemographic characteristics and a clinical history of the participants will be collected. Intervention: Two groups (experimental and control). The experimental group will carry out the ExeRVIEM protocol sessions (6 min) focused on the upper and lower limbs. (2 sessions per week for 8 weeks). All sessions will begin with a warm-up focused on stimulating coordination and joint mobilization, so that the body is predisposed both centrally and peripherally to carry out the session and will end with a stretching routine accompanied by breathing calm and controlled cycles. The session will be supervised by the center's physiotherapist or occupational therapist. The control group will continue with the usual activities proposed by the center team. Evaluations: 3 evaluations will be carried out: initial, final (at 8 weeks) and follow-up (one month after the end of the program). The contents of the evaluations will be: Patient characteristics: "Ad hoc" record sheet that will include data on age, sex, years since diagnosis, MS subtype, and drug treatment. ExeRVIEM protocol. Safety (Simulator Sickness Questionnaire), Usability (System Usability Scale) and personal experiences (Game Experience Questionnaire and "ad hoc" interview notebook) Balance, gait and risk of falling (Tinetti Test) 3. Functional mobility and lower limb strength (Five times sit to stand test) 4. Functional autonomy (Timed Up and Go Test- simple and cognitive) 5. Fatigue (Fatigue Severity Scale) 6 Handgrip (dynamometer) 7. Reaction time (Rezzil Software) Hypothesis: Our findings aim to support the use of new health technologies in the field of rehabilitation and medical care for people with MS, achieving a feasible and safe Immersive Virtual Reality exergaming program.