Active clinical trials for "Machado-Joseph Disease"

The investigators plan to fill the gap between the current state of clinical trial readiness and the optimal one for SCA1 and SCA3, which are fatal rare diseases with no treatments. Through US-European collaborations, the investigators will establish the world's largest cohorts of subjects at the earliest disease stages, who will benefit most from treatments, validate an ability to detect disease onset and early progression by imaging markers, even prior to ataxia onset, and identify clinical trial designs that will generate the most conclusive results on treatment efficacy with small populations of patients.

The primary objective of this study is to evaluate the safety and tolerability of multiple ascending doses of BIIB132 administered via intrathecal (IT) injection to participants with spinocerebellar ataxia type 3 (SCA3). The secondary objective of this study is to characterize the multiple-dose pharmacokinetics (PK) of BIIB132 administered via IT injection to participants with SCA3.

The purpose of this study is to examine the differences in cerebral spinal fluid (CSF) and blood of patients with spinocerebellar ataxias and healthy volunteers. The goal of this project is to identify new biomarkers that are useful for characterizing spinocerebellar ataxias and identify targets for treatment or prevention of this condition.

Few studies evaluated the efficacy of adding weights on the lower limbs in patients with ataxic disorders. There is no current evidence on which would be the most appropriate weight for use in this context. To assess progress and benefits of using this load, gait of symptomatic carriers of spinocerebellar ataxia type 3/Machado Joseph disease the objective of the study is to evaluate the gait with and without different load weights on lower limbs. Outcomes were the Scale for the Assessment and Ataxia Rating of (SARA), kinematic gait assessment by the accelerometer and gyroscope and the Patient Global Impression (PGI) about which weight they prefer for walking.

There are no clinically established treatments which have been proven to delay the disease progression in spinocerebellar ataxia (SCA) 3. Most available treatments are only for symptom alleviation, and thus the majority of patients will eventually progress to needing and wheel chair and eventually bedridden. As trehalose appear to be potentially promising treatment in SCA, the investigators aim to conduct this study using oral trehalose in our genetically confirmed SCA 3 patients.

This is an exploratory, randomized, parallel-group, dose escalation and dose-controlled study without a placebo arm. Eligible patients will be randomized in a 1:1 ratio (double-blind) to receive Cabaletta in 2 doses, once weekly for 22 weeks (total of 24 weeks of treatment).

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 - 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. - 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

Machado-Joseph Disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is the most common spinocerebellar ataxia worldwide.Repetitive transcranial magnetic stimulation (rTMS) is a form of brain stimulation therapy used to treat depression and cerebellar ataxias. In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a 15 day treatment with 1 Hz of repetitive transcranial magnetic stimulation (rTMS) can improve symptoms (motor symptoms and non-motor symptoms) in patients with MJD.

Spinocerebellar ataxia type 3 (SCA3) is one of autosomal dominant hereditary ataxias. Standing imbalance, unsteady gait, dysmetria, fatigue, and depression would occur gradually. There are no effective treatment or palliative methods for patients in the present days. However, low-dose growth hormone, or its downstream product, insulin-like growth factor I (IGF-1), may deter the progress of SCA3 in transgenic mice. The main bioactive constituent among the Chinese medicine WT possesses neuroprotective function against glutamate-induced toxicity, which is one major pathology of SCA3. It promotes neurogenesis, and increases the protein expression of IGF-1 in ischemic brains of rats. Thus, we designed a randomized, double-blind trial for patients with SCA3, if WT is a possible neuroprotective medicine. All the subjects will be recruited from Changhua Christian Hospital. Diagnosis is confirmed by gene test and magnetic resonance image by a neurologist. They will be assigned in random and double blind, prescribed with 3 grams concentrated powder of WT or placebo, twice a day, for 12 weeks. After the washout period of 4 weeks, there will be a crossover of placebo or WT for another 12 weeks. After that, another 4-week rest will be followed by the end of trial. Check items in five check points include: 1. Blood examination (serum IGF-1, Neurofilament light chain, mitochondria copy number, 8_OHdG, delta-Ct), 2.Neurological exam (Scale for the Assessment and Rating of Ataxia), 3. Questionnaires (Modified Fatigue Impact Scale, Epworth Sleepiness Scale), 4. Handgrip strength test (which is correlated to IGF-1 value in elderly), and 5. serum metabolites, . All the data will be disclosed after the end of trial. Paired-T test or Wilcoxon Ranked Sign Test will be operated in SPSS.

To test the effects of low frequency deep rTMS using the novel HCERMJD-coil on cerebellar deficits in patients with SCA3 and to establish its safety in this population. Investigator is anticipate that stimulation of the cerebellum with the novel HCERMJD-coil may induce significantly therapeutic effects in patients with SCA3 and will pave the way for establishing a novel and effective treatment for this disorder.