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Abstract Details

Safety and Efficacy of Lithium Carbonate for the Treatment of Machado-Joseph Disease (MJD/SCA3): A Phase II-III Randomized, Double-Blind, Placebo-Controlled Trial
Movement Disorders
S43 - (-)
004
MJD/SCA3 is a neurogenetic disorder caused by a CAG repeat expansion at the ATXN3 gene leading to progressive loss of motor coordination that is current untreatable. Lithium was shown to exert neuroprotective effects in pre-clinical models of spinocerebellar ataxias and other polyglutamine disorders.
A phase II-III double-blind, placebo-controlled, randomized (1:1; blocks of variable sizes, stratified by CAGexp), clinical trial was conducted. Independently ambulatory MJD/SCA3 patients with 10 years or less of disease duration were enrolled from May to September, 2011 in a single center in Rio Grande do Sul, Brazil. Primary end-point of phase II (24 weeks) was the difference in total N of adverse events (AE) and of phase III (48 weeks), the difference in the variation of the NESSCA score (range: 0-40) between groups.
92 patients were recruited and 62 were randomized, 31 to Lithium and 31 to Placebo. Two patients withdrawn the study after baseline assessments and were excluded from intention-to-treat (ITT) analysis. 169 AE were reported after 24 weeks, 49,7% in Lithium and 50,3% in Placebo groups (IC 95% -0.08 to 0.07, p=1.00), with no differences among mild, moderate or severe AEs. After 24 weeks, in ITT (N=60) and per-protocol analysis (N=56), NESSCA worsened 0.93 (IC 95% -0.173 to 2.032, p=0.097) and 0.91(IC 95% -0.212 to 2.032, p=0.110) points more in Placebo than in Lithium treated patients. Non-dominant click test, PATA rate and SCAFI worsened significantly less in Lithium treated patients (p<0.05), as well as the sub-score of cerebellar items of NESSCA (p=0.009), after 24 weeks (ITT).
This study provides Class 1 evidence that Lithium is safe in SCA3/MJD. Interim results on efficacy must be confirmed with the completion of Phase III.
Authors/Disclosures
Jonas A. Saute, MD
PRESENTER
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Thais Monte No disclosure on file
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Giancarlo Comi, MD (University Vita-Salute) Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aspen Healthcare. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rewind.
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Carlos Rieder Carlos Rieder has nothing to disclose.
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