Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
Condition: Spinocerebellar Ataxia Type 3; Machado Joseph Disease
MeSH terms: Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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
    


Intervention name(s): Lithium Carbonate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 300 mg tablets, starting dose 300 mg/day; Similar shape, color and taste and the same number of tablets from the experimental group
Intervention MeSH terms: Lithium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: spinocerebellar ataxia; Treatment; Lithium carbonate