Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3

Study Overview
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Brief Summary
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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

Official Title
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Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3

Conditions
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Spinocerebellar Ataxia Type 3, Machado Joseph Disease

Intervention / Treatment
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* Drug: Lithium Carbonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior molecular diagnose of SCA3 with determined number of CAG expanded repeat. Not restricted to wheelchair. With disease duration between 2 and 10 years and more than 16 years old. Exclusion Criteria: Signs of cardiopathy, elevated levels of creatinine, transaminases, bilirubins more than 1.5 times the normal upper limit at baseline. History of previous lithium carbonate significant adverse reaction, or drug abuse or alcoholism. Disturbance of thyroid function at baseline. Participation on another clinical trial less than 4 weeks before the study entrance. Current use of valproic acid, memantine, neuroleptics and anticoagulants If the individual (woman) did not agree in utilize a high effective contraceptive method during the study period and 3 months after the study-end.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Similar shape, color and taste and the same number of tablets from the experimental group<br>|
| Experimental: Lithium Carbonate<br> | Drug: Lithium Carbonate<br>* 300 mg tablets, starting dose 300 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 | According to the Common toxicity criteria manual, version 2.0 | 6 months | 
| Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3 | Application of the Neurological Examination Score for SCA 3 (NESSCA) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores | 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 | 6 and 12 months | 
| Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers | BDNF, NSE, HDAC, GSK-3Beta | 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinocerebellar ataxia, Treatment, Lithium carbonate