View clinical trials related to Spinocerebellar Degenerations.
Filter by:The Hereditary Ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Current treatments for Hereditary Ataxias are mainly pharmacological, rehabilitative, or psychological treatments，while no effective treatment available. Stem Cell therapy is a novel and promising therapeutic strategy for Hereditary Ataxias treatment. In this study, the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells transplantation will be evaluated in patients with Hereditary Ataxias.
This is a preliminary study to determine the safety and efficacy of intravenous immune globulin in treating Spinocerebellar Ataxia. The investigators aim to assess changes in clinical measures of disease severity before and after treatment.
The hereditary cerebellar ataxias include diverse neurodegenerative disorders. Hereditary ataxias can be divided into autosomal dominant ataxias (ADCAs), autosomal recessive ataxias (ARCAs), X-linked, and mitochondrial ataxias on the basis of mode of inheritance. The key feature in all these disorders is ataxia typically characterised by poor balance, hand incoordination, postural or kinetic tremor, dysarthria and dysphagia. To date no treatment has been shown to slow progression of the disease and symptomatic therapies are limited to few options that are partially effective. Purkinje cells project inhibitory signals to the deep cerebellar nuclei(DCN) which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement, while uncontrolled spontaneous firing of DCN neurons may underlay cerebellar ataxia. Recent studies have demonstrated that small-conductance calcium-activated potassium (SK) channels inhibitor are able to increase DCN firing rate. Since SK channels are critical regulators of DCN firing rate, SK openers such as the drug riluzole may reduce neuronal hyperexcitability and thereby be useful in the therapy of cerebellar ataxia. On this base the investigators published a pilot study in patients with chronic cerebellar ataxia (Ristori et al., Neurology 2010) investigating safety and efficacy of riluzole or placebo administration for 8 weeks. The results demonstrated a significative improvement in International Cooperative Ataxia Rating Scale (ICARS) global score after four weeks and after 8 weeks in the riluzole arm. The present protocol is aimed at verifying the safety and efficacy of riluzole administration for a longer period, in a larger sample size of patients, with more stringent diagnostic criteria (hereditary cerebellar ataxia), respect to the above pilot study. Sixty patients will be enrolled in a double-blind, placebo-controlled trial. By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 12 months. Treatment effects will be assessed by comparing the Scale for the Assessment and Rating of Ataxia (SARA) before treatment and during therapy at months 3 and 12.
DESIGN: Pilot, Phase II, double-blind, placebo-controlled study JUSTIFICATION: In the literature one does not find a pharmacological treatment that changes the natural history of Spinocerebellar ataxtia type 3 (SCA3). Patients with this disease invariably become dependent. OBJECTIVES I. To determine safety and tolerability of phenylbutyrate in patients with SCA3. II. To provide early subsidies on the efficacy of phenylbutyrate in SCA3. DURATION: 12 months of a double-blind study. PLACE OF REALIZATION: Hospital de Clínicas de Porto Alegre, Brazil. NUMBER OF PATIENTS: 20 patients. CONCOMITANT MEDICATIONS: There are no concomitant medications that are prohibited unless they affect safety parameters of this study (hemogram and platelets; fasting serum glucose, AST, ALT, Gamma-GT, Bilirubins, Prothrombin time, Creatinine, Urea, Na, K, chlorides and arterial gasometry; electrocardiogram and echocardiogram). MEDICATIONS UNDER INVESTIGATION: Powdered sodium phenylbutyrate in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets) and may be reduced in case of mild adverse events. OUTCOMES Primary safety outcome: The number of adverse events, interruptions and dose reductions in the two groups (cases and controls). Efficacy outcomes: Efficacy outcomes are the following scores in both groups: NESSCA, SARA, Barthel, BDI, and WHOQol.
Design: Phase II-III, double-blind, parallel, placebo controlled randomized Clinical trial Background: Spinocerebellar ataxia type 3 (SCA-3) is an autosomal dominant adult-onset neurodegenerative disorder for which there is no current treatment. Patients will invariably become dependent from others and unable to walk during the disease course. Hypothesis: Lithium Carbonate is safe and effective in treating neurological symptoms and improving quality of life of patients with SCA3. Outcomes: Primary - Phase 2 - To assess safety and tolerability of Lithium Carbonate in patients with SCA3 after 6 months of follow-up - Phase 3 (if Phase II study shows safety of therapy) - To assess efficacy of Lithium Carbonate in patients with SCA3 through the Neurological Examination Score for SCA 3 (NESSCA) after 12 months of follow-up . Secondary 1. - To assess efficacy on neurological function, ataxic, depressive and quality of life scores of Lithium Carbonate in patients with SCA3 through the Scale for the Assessment and Rating of Ataxia (SARA), 9-Hole Peg Board test, 8m walking time, PATA repetition rate, Click Test, SCA Functional Index (SCAFI), Composite Cerebellar Functional Score (CCFS), Beck Depression Inventory, Barthel Index and WHOQol after 6 and 12 months of follow-up. 2. - To assess the effect of Lithium Carbonate in peripheral levels and expression of treatment biomarkers (BDNF, NSE, HDAC, GSK-3Beta) Study Duration: 12 months - Final analysis of phase 2 (safety study) at 6 months with continuous monitoring until the end of phase 3 (efficacy study). - Preliminary analysis of efficacy on ataxia scales at 6 months of study and final analysis of phase 3 at 12 months. Obs: A futility analysis will be performed after 12 months of therapy if no statistically significant difference between groups were found. This analysis will define if the study will continue until 18 or 24 months of follow-up or will be ended at 12 months. Location: Hospital de Clínicas de Porto Alegre Subjects: 60 molecularly diagnosed SCA3 patients from the outpatient unit of the Medical Genetics Service of Hospital de Clínicas de Porto Alegre Intervention: Lithium Carbonate tablets of 300mg. Starting dose will be 300mg/day with drug titration during 49 days or until achieving the defined target lithium serum level of 0.5 to 0.8 mEq/L
Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCA and this study will focus on types 1, 2,3, and 6 (SCA 1, SCA 2, SCA 3 , also known as Machado-Joseph disease and SCA 6). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease. The research questions are: 1. How does your disease progress over time? 2. What are the best ways to measure the progression? 3. Do some genes, other than the gene that is abnormal in your disease, have any effect on the way the disease behaves? This is a nationwide study and we expect that 800 patients will participate all over the USA. The participants will be in the study for an indeterminate period of time. Study visits will be done every 6 or 12 months depending on the participating site.
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of autosomal dominantly inherited progressive ataxia disorders. It is estimated that there are 30,000 individuals in the European Community that directly descend from individuals affected by a SCA disorder and thus carry a 50% risk of having inherited an SCA mutation. These at risk individuals provide a unique research opportunity to prospectively study the presymptomatic phase of SCA disorders and to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. This information is of critical importance for the development of future therapeutic interventions aimed at postponing the clinical onset of ataxia. We therefore propose to perform a prospective observational study of individuals at risk for the most common SCA disorders, SCA1, SCA2, SCA3 and SCA6 (RISCA). It is our aim to answer the following questions: (1) What is the incidence of disease manifestation in mutation carriers? (2) Which clinical signs precede the onset of manifest ataxia in SCA1, SCA2, SCA3 and SCA6? (3) What are the prevalence and incidence of preceding signs? (4) Are the prevalence and incidence of preceding signs affected by genotype, gender, age, estimated time until disease manifestation and repeat length? (5) Does the presence of certain preceding signs predict the manifestation of ataxia ? (6) Are there MRI alterations that precede the onset of ataxia? It is planned to enroll 480 study participants and to follow them at regular intervals over six years. At each visit, study participants are asked in a structured interview for a number of predefined clinical signs that potentially precede the onset of ataxia. In addition, the following self-assessment scales will be applied: Pittsburgh Sleep Quality Index (PSQI), Diagnostic Criteria for Restless Legs Syndrome, Patient´s Health Questionnaire (PHQ-9). All study participants will undergo a physical examination including the Scale for the Assessment and Rating of Ataxia (SARA). Study participants will further perform the SCA Functional Composite (SCA-FC) which is a comprehensive measure of functional capacity based on results in quantitative tests related to gait (8m timed walk), speech (PATA rate) and hand function (9 hole pegboard). In a subset of study participants, we will record eye movements and obtain volumetric MRIs. The study will also be used to collect and store blood and urine samples for proteomic and gene expression studies. RISCA is conducted by the Ataxia Study Group (ASG). It relies on the network structure created by the EUROSCA project.
To evaluate the efficacy and safety of KPS-0373 in patients with SCD.
The purpose of this study is to determine safety and tolerability of the treatment with lithium in Spinocerebellar Ataxia 2. Moreover, clinical symptoms, neuronal loss, quality of life and depressive symptoms, will be considered to further investigate the effect of lithium therapy.
Spinocerebellar ataxia (SCA) is a group of inherited disorders characterized by cerebellar degeneration leading to imbalance, incoordination, speech difficulties and problems with walking. Recently, individual case reports have suggested that varenicline, a drug used in smoking cessation, produces substantial improvement in patients with several inherited ataxias. A modest response was noted in 5 patients with SCA, suggesting that it is potentially efficacious in this disorder as well. Although this agent is available for off-label use, the severe side effects noted with its use and the lack of long-term toxicity data demand that it be systematically assessed. The present study will test whether varenicline is safe and potentially efficacious in a heterogeneous cohort of adults with SCA.