Active clinical trials for "Neuromyelitis Optica"

Neuromyelitis optica (NMO) is an autoimmune disease that affects the central nervous system. Patients have relapses (also known as attacks) which are often quite severe and leave them with significant disability. Without treatment, within 5 years 50% of NMO patients are blind in one or both eyes or require walking assistance (cane, walker or wheelchair). NMO has only been relatively recently described and is fairly rare. Most NMO patients' immune systems produce abnormal antibodies against aquaporin-4 (AQP4), which is found in certain cells in the central nervous system. When these AQP4 antibodies bind to AQP4, they trigger a cascade of events involving the immune system which eventually leads to damage to the nervous system. This ultimately leads to disability, some of which is permanent. Until now, treatments for NMO have been mostly focused on decreasing production of this AQP4 antibody. However, recent experiments in animal models of NMO have shown the importance of what happens inside the central nervous system after the antibody binds to the nervous system cell. Specifically, researchers have noted the importance of a specific cell type, eosinophils, in causing damage in NMO lesions. In a recent study, researchers showed they could prevent damage from NMO by blocking eosinophils using cetirizine, which is a popular over-the-counter allergy medicine. Cetirizine is already known to be safe and well-tolerated in the general population. In this study, the researchers plan to add cetirizine on to patients' current NMO treatment. The researchers aim to show that it is safe, well-tolerated, and that with cetirizine, NMO patients have less relapses and therefore less disability over the course of the year following initiation of treatment. The researchers also plan to study how cetirizine changes the immunological profile in NMO patients by examining blood and cerebrospinal fluid.

Transverse myelitis (TM) is an inflammatory disorder of the spinal cord that leads to disabilities of gait. Dalfampridine, a sustained-release potassium inhibitor has been shown to be effective in improving gait and other neurologic functions in multiple sclerosis. Dalfampridine has the potential to improve neurologic function in patients with transverse myelitis as this rare disorder shares a similar pathogenic process with multiple sclerosis. The in a clinical trial to test the efficacy of dalfampridine in TM. The clinical trial that the investigators propose to conduct will focus on TM and will evaluate the dalfampridine in primary neurologic outcome, 25-foot timed walk, and several secondary outcomes including valid behavioral and neurophysiological tests. This is a re-launch of the previous trial, which now includes additional behavioral and clinical testing.

The purpose of this study is to compare annual relapse rate, expanded disability status scale, and side effects of azathioprine and rituximab in patients with neuromyelitis optica spectrum disorder during a one year follow up through a randomized clinical trial.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized by relapsing optic neuritis and longitudinal extensive transverse myelitis. The specific autoantibody against aquaporin 4 (AQP4-ab) has been suggested to contribute to the pathogenesis of the disease. Peripheral blood plasma cells are a major source of AQP4-ab. Previous studies have observed increased IL-6 levels in serum and cerebrospinal fluid of patients with NMOSD, particularly during relapses. Exogenous interleukin (IL)-6 promotes the survival of plasma cells and their production of AQP4-ab in vitro. And blockade of IL-6 receptor signaling by an anti-IL-6 receptor antibody reduces the survival of plasma cells in vitro. Tocilizumab (ACTEMRA®), a humanized monoclonal antibody against the IL-6 receptor, has shown beneficial clinical effects in some patients with NMOSD when concomitant immunosuppressive medications were administered. However, the long-lasting biological effects of preceding immunotherapies such as rituximab might overlap with the subsequent tocilizumab therapy. To reduce the side effects of concomitant treatments to large extent and verify the beneficial effects of tocilizumab, we evaluate the safety and efficacy of tocilizumab as monotherapy in patients with NMOSD.

A novel technology called Scrambler Therapy is a non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of C fibers with the intent of re-organizing maladaptive signaling pathways. This neuromodulatory therapy has been investigated for treatment of chronic neuropathic pain in several conditions including chemotherapy-induced peripheral neuropathy, post-herpetic neuralgia and post-surgical neuropathic pain with promising results. Patients report sustained relief after undergoing daily treatment sessions for 10 consecutive weekdays. This study is a randomized single blinded, sham-controlled trial of patients with Neuromyelitis Optica Spectrum Disorder who have central neuropathic pain using Scrambler Therapy added to standardized empiric medications using patient reported outcomes to determine if Scrambler Therapy is a feasible and effective add-on treatment of chronic neuropathic pain. This trial will recruit twenty-two adult patients diagnosed with NMOSD who have chronic neuropathic pain despite empiric treatment with an anti-epileptic, antidepressant, opioid and/or an NSAID medication. Patients will be randomized 1:1 to undergo Scrambler Therapy or blinded sham daily for 10 days. The primary outcomes will be acceptability and feasibility. The secondary outcome will be efficacy measured as a change in pain scores of more than two points recorded daily by the patient using an 11-point visual analog scale; quality of life (QoL), neurologic function, anxiety, depression, sleep disturbance and pain will also be evaluated at baseline, at the end of therapy, and at 4 & 8 weeks following completion of treatment. Investigators hypothesize that Scrambler Therapy will be an acceptable, feasible and efficacious intervention that significantly reduces pain in patients with neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory autoimmune conditions of the central nervous system (CNS) . The discovery of NMOSD-specific aquaporin 4 (AQP4) antibody has established that NMOSD is indeed a distinct entity . Approximately 80% of patients with NMOSD test positive for aquaporin-4 (AQP4) immunoglobulin G (IgG) antibodies .AQP4-IgG associated NMOSD appears to target astrocytes, not myelin, leading to elevated markers of astrocyte injury during attacks . Untill now there is limited research about understanding the biomarkers of astrocyte injury and the following reactive gliosis. Family with sequence similarity 19-memberA5 (FAM19A5) protein is postulated to regulate nervous and immune cells of the brain as a brain-specific chemokine, but its precise functional role is not well understood . A recent study suggested that FAM19A5 is secreted by reactive astrocytes following CNS damage and triggers reactive gliosis . In another recent study, serum FAM19A5 was higher in patients with NMOSD-AQP4 than in other CNS demyelinating diseases and healthy controls . So, we need to study the level of this novel biomarker among our Egyptian NMOSD patients and whether it shall be a new biomarker for NMOSD . Moreover just few studies conducted on cognitive dysfunctions in NMOSD patients and they demonstrate a significant decrease of cognitive abilities and the prevalence of CI in different samples varies between 30 and 70% .So further studies are needed to investigate the cognitive performance in NMOSD patients

This is a prospective non interventional study including patients with Relapsing-Remitting Multiple Sclerosis (RRMS) or with Neuromyelitis Optica Spectrum Disorders (NMOSD) and healthy subjects, who are enrolled within the routinely programmed clinical examinations at the IRCCS Neuromed (Pozzilli, Italy), IRCCS Polyclinic Hospital San Martino (Genoa, Italy) and Sant'Andrea Hospital - University of Rome La Sapienza (Rome, Italy). Specifically, the study investigates how ozanimod may contrast neurodegenerative mechanisms triggered by both arms of the adaptive immune response (T and B cells) and by their suboptimal regulation in MS. Overall, the project aims at assessing by in vitro experiments (there will be no patients on treatment with ozanimod and the drug will be only used in vitro): AIM1: ozanimod ability to modulate the synaptotoxic effect of T-cells derived from patients with MS relapse in a MS-chimeric ex-vivo model and to identify possible mediators (IRCCS Neuromed-Pozzilli, in collaboration with Synaptic Immunopathology Laboratory Dep. Systems Medicine, Tor Vergata University of Rome); AIM2: ozanimod ability to reduce the cytokine-mediated breakdown of the BBB and the migration of the here studied immune cells through ex vivo models of BBB (IRCCS Polyclinic Hospital San Martino); AIM3: ozanimod ability to affect the migration properties of Epstein Barr virus (EBV) infected B cells in MS (Sant'Andrea Hospital); AIM4: ozanimod ability to modulate the number and/or function of regulatory T cells (Treg), a lymphocyte population playing a key role in the control of pathogenic adaptive immune responses (Treg Cell Laboratory, Università degli Studi di Napoli "Federico II", Naples, Italy, receiving blood samples from Neuromed Hospital and Sant'Andrea Hospital; not recruiting unit). The work of the four labs is conceptually and operationally integrated: the labs at IRCCS Neuromed-Pozzilli/Tor Vergata University (Aim1) and at Polyclinic Hospital San Martino (Aim2) will investigate the effects of ozanimod on well-known mechanisms of damage in MS, inflammatory synaptopathy and BBB damage and immune cell migration. The lab at Sant'Andrea Hospital (Aim3), will verify whether B cells infected by different EBV genotypes are involved in BBB migration, and how ozanimod may interfere with this mechanism. The Treg Cell Laboratory (Aim4) will investigate whether ozanimod can also act "upstream" of these mechanisms by regulating the adaptive immune response.

This is a phase 1b interventional trial of bevacizumab (Avastin®) to evaluate the tolerability/safety and preliminary efficacy of bevacizumab (Avastin®) as add-on therapy for treatment of acute optic neuritis and/or transverse myelitis in neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD). A single infusion of Avastin® is added to standard-of-care high dose steroids and an additional dose of Avastin® is added to plasma exchange (if necessary). The primary outcomes are clinical changes in the Expanded Disability Severity Scale, Timed 25-foot Walk and Low Contrast Visual Acuity, MRI parameters and safety.

First in human study to assess the tolerability and safety profile of treatment with dendritic cell in patients with multiple sclerosis or neuromyelitis optica.

Patients diagnosed with anti-aquaporin 4 antibody positive Neuromyelitis Optica spectrum disorder were confirmed based on diagnostic criteria. Patients who meet all inclusion criteria and do not conflict with the exclusion criteria will receive steroid plus therapy （1g/day for five consecutive days）. Subsequently, patients who not provided adequate effect of therapy to steroids plus therapy will receive NPB-01 (intravenous immunoglobulin) 400mg/kg/day for five consecutive days. Patients evaluated Quantification of nerve and spinal cord impairment （QOSI） and the Expanded Disability Status Scale （EDSS）/ Functional Systems （FS） and anti-aquaporin 4 antibody et al. As a safety endpoint, the safety of NPB-01 will be investigated the occurrence of adverse events by one year after the start of the study treatment.