Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 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


Eligibility: 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.

Relevance to patient case: not relevant