title: A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease.
abstract: BACKGROUND
  Because lithium exerts neuroprotective effects in preclinical models of polyglutamine disorders, our objective was to assess the safety and efficacy of lithium carbonate (0.5-0.8 milliequivalents per liter) in patients with Machado-Joseph disease (spinocerebellar ataxia type 3 [MJD/SCA3]).
  
  
  METHODS
  For this phase 2, single-center, double-blind, parallel, placebo-controlled trial (ClinicalTrials.gov identifier NCT01096082), 62 patients who had MJD/SCA3 with a disease duration ≤10 years and an independent gait were randomly assigned (1:1) to receive either lithium or placebo.
  
  
  RESULTS
  After 24 weeks, 169 adverse events were reported, including 50.3% in the lithium group (P = 1.00; primary safety outcome). Sixty patients (31 in the placebo group and 29 in the lithium group) were analyzed for efficacy (intention-to-treat analysis). Mean progression between groups did not differ according to scores on the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) after 48 weeks (-0.35; 95% confidence interval, -1.7 to 1.0; primary efficacy outcome). The lithium group exhibited minor progression on the PATA speech-rate (P = 0.002), the nondominant Click Test (P = 0.023), the Spinocerebellar Ataxia Functional Index (P = 0.003), and the Composite Cerebellar Functional Score (P = 0.029).
  
  
  CONCLUSIONS
  Lithium was safe and well tolerated, but it had no effect on progression when measured using the NESSCA in patients with MJD/SCA3. This slowdown in secondary outcomes deserves further clarification.
authors.affiliation: Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Jonas Alex Morales
authors.initials: JA
authors.lastname: Saute
authors.forename: Raphael Machado
authors.initials: RM
authors.lastname: de Castilhos
authors.forename: Thais Lampert
authors.initials: TL
authors.lastname: Monte
authors.forename: Artur Francisco
authors.initials: AF
authors.lastname: Schumacher-Schuh
authors.forename: Karina Carvalho
authors.initials: KC
authors.lastname: Donis
authors.forename: Rui
authors.initials: R
authors.lastname: D'Ávila
authors.forename: Gabriele Nunes
authors.initials: GN
authors.lastname: Souza
authors.forename: Aline Dutra
authors.initials: AD
authors.lastname: Russo
authors.forename: Gabriel Vasata
authors.initials: GV
authors.lastname: Furtado
authors.forename: Tailise Conte
authors.initials: TC
authors.lastname: Gheno
authors.forename: Diogo Onofre Gomes
authors.initials: DO
authors.lastname: de Souza
authors.forename: Luis Valmor Cruz
authors.initials: LV
authors.lastname: Portela
authors.forename: Maria-Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Suzi Alvez
authors.initials: SA
authors.lastname: Camey
authors.forename: Vanessa Bielefeld Leotti
authors.initials: VB
authors.lastname: Torman
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: de Mello Rieder
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D017827:Machado-Joseph Disease / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D016651:Lithium Carbonate
keywords: Machado-Joseph disease; clinical trial; lithium; polyglutamine disorders; spinocerebellar ataxias