Details

Autor(en) / Beteiligte

• Saute, Jonas Alex Morales
• de Castilhos, Raphael Machado
• Monte, Thais Lampert
• Schumacher-Schuh, Artur Francisco
• Donis, Karina Carvalho
• D'Ávila, Rui
• Souza, Gabriele Nunes
• Russo, Aline Dutra
• Furtado, Gabriel Vasata
• Gheno, Tailise Conte
• de Souza, Diogo Onofre Gomes
• Portela, Luis Valmor Cruz
• Saraiva-Pereira, Maria-Luiza
• Camey, Suzi Alvez
• Torman, Vanessa Bielefeld Leotti
• de Mello Rieder, Carlos Roberto
• Jardim, Laura Bannach

Titel

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

Ist Teil von

• Movement disorders, 2014-04, Vol.29 (4), p.568-573

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. © 2014 International Parkinson and Movement Disorder Society