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: Jonas Alex Morales Saute, Raphael Machado de Castilhos, Thais Lampert Monte, Artur Francisco Schumacher-Schuh, Karina Carvalho Donis, Rui D'Ávila, Gabriele Nunes Souza, Aline Dutra Russo, Gabriel Vasata Furtado, Tailise Conte Gheno, Diogo Onofre Gomes de Souza, Luis Valmor Cruz Portela, Maria-Luiza Saraiva-Pereira, Suzi Alvez Camey, Vanessa Bielefeld Leotti Torman, Carlos Roberto de Mello Rieder, Laura Bannach Jardim
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 29 Issue 4 Pg. 568-73 (Apr 2014) ISSN: 1531-8257 [Electronic] United States
• PMID: 24399647 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 International Parkinson and Movement Disorder Society.

Chemical References

• Enzyme Inhibitors
• Lithium Carbonate

Topics

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