Abstract Details

Title 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

Topic Movement Disorders

Presentation(s) S43 - (-)

Poster/Presentation
Number 004

Background 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.

Objective

Design/Methods 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.

Results 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 Two patients withdrawn the study after baseline assessments and were excluded from intention-to-treat (ITT) analysis. 169 AE were reported after 24 weeks, 49,7% in Lithium and 50,3%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).

Conclusions 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	No disclosure on file
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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.
	No disclosure on file

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