A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease

Mov Disord. 2014 Apr;29(4):568-73. doi: 10.1002/mds.25803. Epub 2014 Jan 7.


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.

Keywords: Machado-Joseph disease; clinical trial; lithium; polyglutamine disorders; spinocerebellar ataxias.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Lithium Carbonate / adverse effects
  • Lithium Carbonate / therapeutic use*
  • Machado-Joseph Disease / drug therapy*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Enzyme Inhibitors
  • Lithium Carbonate

Associated data

  • ClinicalTrials.gov/NCT01096082