Tenofovir Alafenamide for Treatment of Symptoms and Neuroprotection in Relapsing Remitting Multiple Sclerosis
As the in vivo reservoir of the Epstein-Barr virus, B cells play an important role in the perpetuation of MS disease activity. B cell depletion therapy with medications like ocrelizumab or rituximab have proved very successful in preventing clinical relapses and MRI activity in MS, but incomplete in terms of neuroprotection and symptomatic outcomes. Ocrelizumab and rituximab only target naïve and memory B cells expressing the CD20 marker but do not deplete the wide spectrum of B cell lineages including plasmablasts and plasma cells, which are also key reservoirs for EBV. This is particularly relevant to the mechanism of action of TAF, since EBV lytic reactivation occurs in coordination with B-cell differentiation. In vivo, the initiation of plasma cell differentiation provides the physiological trigger for EBV lytic reactivation, and EBV utilizes the plasma cell differentiation program to replicate. As these cells are ineffectively depleted by anti-CD20 treatment, the use of TAF would be highly complementary as an add-on treatment to anti-CD20 therapy. Anti-EBV therapy with TAF in combination with ocrelizumab or rituximab will therefore provide a synergistic approach to cover the whole EBV reservoir. The primary aims of the proposed trial are to determine if TAF, at the standard dose of 25 mg/day administered for 12 months: i) is safe and well-tolerated by individuals with RRMS over a period of treatment of 12 months; ii) leads to an overall improvement in fatigue, as assessed by the Modified Fatigue Impact Scale by 12 months; and iii) causes a reduction in serum concentrations of neurofilament light chain (NfL), a marker of neuronal damage in MS.
NCT04880577 — Fatigue
Status: Withdrawn
http://inclinicaltrials.com/fatigue/NCT04880577/
A Phase 2, Double-blind, Randomized, Placebo-controlled Study Assessing Efficacy and Safety of SAR441344, a CD40L-antagonist Monoclonal Antibody, in Participants With Relapsing Multiple Sclerosis
Primary Objective: To determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions Secondary Objective: - To evaluate efficacy of SAR441344 on disease activity as assessed by other MRI measures - To evaluate the safety and tolerability of SAR441344 - To evaluate pharmacokinetics of SAR441344
NCT04879628 — Multiple Sclerosis
Status: Active, not recruiting
http://inclinicaltrials.com/multiple-sclerosis/NCT04879628/
A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Ocrelizumab in Patients With Radiologically Isolated Syndrome
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 4 study in which eligible patients with RADIOLOGICALLY ISOLATED SYNDROME (RIS) (as defined by meeting 2017 McDonald criteria for DIS) will be randomized 1:1 to receive ocrelizumab treatment or placebo (standard of care).
NCT04877457 — Multiple Sclerosis
Status: Terminated
http://inclinicaltrials.com/multiple-sclerosis/NCT04877457/
Eye Movement Desensitization and Reprocessing for Depressed People With Multiple Sclerosis: A Pilot Study
Several studies have reported high rates of depression in people with MS. Depressive symptoms represent a serious threat to quality of life and well-being. Furthermore, findings from the literature suggest that mechanisms underneath depressive features and loss of physical functions in MS could be related. The current study aims at investigating the feasibility of a fairly new type of psychotherapy known as "eye movement desensitization and reprocessing" (EMDR) on depression in people with MS. The goal of this intervention is to reduce the long-lasting effects of distressing memories by developing more adaptive coping mechanisms, through bilateral sensory stimulation. Together with the study on clinical measures, brain mechanisms of change will be assessed with MRI. Fifteen depressed or mildly depressed people with MS will be recruited. Participants will be assessed for depression, and quality of life, before and after the intervention. Participants will also undergo an MRI for brain structural and functional assessments before and after the EMDR intervention. The main aim of the study is to verify that EMDR is a feasible psychotherapeutic approach for people with depression and MS and to collect preliminary data on the efficacy of this type of intervention in reducing the depressive symptoms and improving the quality of life. The study, however, will not be limited to the analysis of outcome differences. The use of MRI assessments, in fact, will allow to explore possible brain change modifications related to depression reduction and/or symptoms modifications.
NCT04875832 — Depression
Status: Not yet recruiting
http://inclinicaltrials.com/depression/NCT04875832/
From Genetics to Transcriptomics to Unravel the Mechanisms Behind a Poor Outcome in Multiple Sclerosis
MS is a heterogeneous disease either in its response to treatment or clinical manifestation. Indeed, the natural history of MS is varying from a benign condition to a devastating and rapidly incapacitating disease. Clinical heterogeneity could also be cellular and / or molecular. The aim is to identify from OMIC analyses, at the early stage of the disease, differentially expressed molecules and / or cell subpopulations derived from CD8 + T lymphocytes and / or CD4 + T lymphocytes and / or B lymphocytes and monocytes from patients with aggressive versus non-aggressive, compared to a cohort of healthy controls
NCT04873492 — Multiple Sclerosis
Status: Recruiting
http://inclinicaltrials.com/multiple-sclerosis/NCT04873492/
Prevalence of Coronavirus Disease 2019 in People With Multiple Sclerosis Taking Disease Modifying Therapies in England
The COVID-19 pandemic is a major concern for people on long-term treatments that modify the immune system function. People with multiple sclerosis (pwMS) form a large group who receive such treatments called disease modifying therapies (DMTs). Several types of DMTs with different effects on the immune system are being used for multiple sclerosis (MS). In the absence of large-scale national studies, the risk of COVID-19 among pwMS on various DMTs has not been established. A few physician-reported registry-based studies have suggested that anti-CD20 monoclonal antibodies, such as ocrelizumab and rituximab, used in the treatment of MS can increase the risk of COVID-19. However, in our community-based COVID-19 study of a large cohort of pwMS as part of the UK MS Register, we could not demonstrate an association between DMTs and susceptibility to COVID-19. Other studies have not found any relationship between DMTs and the outcome of COVID-19 among pwMS. To our knowledge, UK is the only country in the world that collects national data on DMT use, providing us with the opportunity to investigate the impact of DMTs on COVID-19 susceptibility and severity in a large population of pwMS. In England, no DMT is being dispensed without prior approval and specialised commissioning by the national Health Services (NHS) England & NHS Improvement (NHSE/I). The scheme, currently implemented in over 100 NHS Trusts in England, ensures that treatment decisions are made in line with agreed commissioning policy and are evidence-based. NHSE/I also has access to Public Health England (PHE) held data on all people who have had a SARS-CoV-2 test. By identifying all pwMS on DMTs and all those who have had a test for coronavirus and collecting data on the clinical outcome of their COVID-19 from their local NHS hospitals, we would be able to establish the risk of COVID-19 and the risk of contracting the infection associated with different DMTs. The findings of the study will help MS clinical teams address the concerns of pwMS about taking DMTs during the COVID-19 pandemic and update their guidelines on the measures pwMS need to take during these unprecedented times.
NCT04863586 — Multiple Sclerosis
Status: Enrolling by invitation
http://inclinicaltrials.com/multiple-sclerosis/NCT04863586/
The Impact of the COVID-19 Pandemic on the Reporting and Management of Multiple Sclerosis Relapses
Throughout the COVID-19 pandemic, and to our knowledge there have been no studies looking systematically at the occurrence of MS relapses and their subsequent management, during the peak of the first wave of the pandemic. In this study we will explore how MS relapses were reported and managed during April - June 2020, compared to a control cohort who experienced a relapse during the same period in 2019 across 5 UK centers.
NCT04858763 — Multiple Sclerosis
Status: Not yet recruiting
http://inclinicaltrials.com/multiple-sclerosis/NCT04858763/
Deficient T Regulatory Cell (Treg) Function in Patients With Relapsing Remitting Multiple Sclerosis
The purpose of this research is to find out how the T regulatory (Treg) cells control autoimmune response in multiple sclerosis. The investigators will identify Treg molecular markers and changes in function in patients with relapse remitting multiple sclerosis (RRMS). The investigators plan to study T regulatory immune cells in the blood of RRMS patients and control subjects to examine how Treg immune cells' deficient function may be involved in the development of mulitple sclerosis.
NCT04857489 — Relapse Remitting Multiple Sclerosis
Status: Recruiting
http://inclinicaltrials.com/relapse-remitting-multiple-sclerosis/NCT04857489/
Symptom Burden in Patients Treated With Ocrelizumab for Multiple Sclerosis
This study is designed to determine whether symptom burden differs by time to infusion.
NCT04855617 — Multiple Sclerosis
Status: Completed
http://inclinicaltrials.com/multiple-sclerosis/NCT04855617/
Investigation of the Effects of Selective Exercise Training on Muscle Architecture, Balance, Function and Fatigue in Multiple Sclerosis
Selective exercise programs specific to muscle groups, with the workload to be done in line with the muscle's own structure, can enable more strength to be released with less fatigue in MS, and this increase in strength can increase balance and functional activities. to determine the effects of type training (selective exercise training), eccentric and concentric training on function, balance, fatigue and muscle architecture.
NCT04853654 — Multiple Sclerosis
Status: Completed
http://inclinicaltrials.com/multiple-sclerosis/NCT04853654/