Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
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.
- 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 .
- - 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
|Spinocerebellar Ataxia Type 3 Machado Joseph Disease||Drug: Lithium Carbonate Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3|
- Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 6 months ]According to the Common toxicity criteria manual, version 2.0
- Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 12 months ]Application of the Neurological Examination Score for SCA 3 (NESSCA)
- Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores [ Time Frame: 6 and 12 months ]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
- Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers [ Time Frame: 3 and 6 months ]BDNF, NSE, HDAC, GSK-3Beta
|Study Start Date:||May 2011|
|Study Completion Date:||January 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Similar shape, color and taste and the same number of tablets from the experimental group
|Experimental: Lithium Carbonate||
Drug: Lithium Carbonate
300 mg tablets, starting dose 300 mg/day
Please refer to this study by its ClinicalTrials.gov identifier: NCT01096082
|Hospital de Clínicas de Porto Alegre|
|Porto Alegre, Rio Grande do Sul, Brazil, 90035-903|
|Principal Investigator:||Laura B Jardim, MD PhD||Medical Genetics Service Hospital de Clinicas de Porto Alegre|
|Study Director:||Jonas AM Saute, MD||Neurology Service Hospital de Clínicas de Porto Alegre|