A randomized controlled pilot trial of lithium in spinocerebellar ataxia type 2 (original) (raw)

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder. Lithium is able to stimulate autophagy, and to reduce Ca2+ efflux from the inositol-1,4,5-triphosphate receptor. We designed a phase II, randomized, placebo-controlled, double-blind, 48-week trial with lithium carbonate in 20 patients with SCA2. The primary objective was to determine safety and tolerability of lithium. The secondary objectives were to determine disease progression, quality of life, mood, and brain volume change. Sixteen patients completed the trial, 8 randomized to lithium, 8 to placebo. Forty adverse events (AEs) were reported during the trial, twenty-eight in the lithium and 12 in the placebo group (p = 0.11). Mean AE duration was 57.4 ± 60.8 and 77.4 ± 68.5 days (p = 0.37). Non-significant differences were observed for the SARA and for brain volume change, whereas a significant reduction in the BDI-II was observed for lithium group (p < 0.05). Lithium was well tolerated and reported AEs were similar to those previously described for bipolar disorder patients. A correctly powered phase III trial is needed to assess if lithium may slow disease progression in SCA2.

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Acknowledgments

The study was supported by a grant from “Associazione Italiana per la lotta alle Sindromi Atassiche (AISA) sez. Campania” to FS, and a grant from the Italian Ministry of Education, University and Research, project PRIN 2010–2011 20108WT59Y_007 to GDM. We are extremely grateful to AISA’s regional president Paolo Zengara for his support in the entire study. We thank Dr. Ettore Brunello Florio from the “Farmacia Florio Dr. Ettore SNC” pharmacy for the knowledge, assistance, and expertise in the pharmaceutical preparation of lithium and placebo. This study was supported by a research grant from POR CREME B25B09000050007.

Conflicts of interest

The authors declare no conflict of interest for the present manuscript.

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Authors and Affiliations

  1. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II, Via Pansini, 5, 80131, Napoli, NA, Italy
    Francesco Saccà, Giorgia Puorro, Mariafulvia de Leva, Angela Marsili, Chiara Pane, Cinzia Valeria Russo, Giuseppe De Michele, Alessandro Filla & Vincenzo Brescia Morra
  2. Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy
    Arturo Brunetti
  3. Division of Nephrology, Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
    Giovambattista Capasso & Francesco Trepiccione
  4. Biostructure and Bioimaging Institute, National Research Council, Naples, Italy
    Amedeo Cervo, Sirio Cocozza & Mario Quarantelli

Authors

  1. Francesco Saccà
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  2. Giorgia Puorro
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  3. Arturo Brunetti
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  4. Giovambattista Capasso
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  5. Amedeo Cervo
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  6. Sirio Cocozza
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  7. Mariafulvia de Leva
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  8. Angela Marsili
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  9. Chiara Pane
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  10. Mario Quarantelli
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  11. Cinzia Valeria Russo
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  12. Francesco Trepiccione
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  13. Giuseppe De Michele
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  14. Alessandro Filla
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  15. Vincenzo Brescia Morra
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Corresponding author

Correspondence toFrancesco Saccà.

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415_2014_7551_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 4722 kb) Figure 2 Box and whiskers plot. Box shows quartile 1 to 3 and median; whiskers show quartile 1–1.5 of the interquartile range (IQR) and quartile 3 +1.5 the IQR. Circle; outlier >1.5 and <3 times the IQR. # = p<0.01. ## = p<0.001. Figure 3 Urine osmolality was evaluated in the first void sample after a night-long water deprived period to assess the maximal urine concentration ability. Box and whiskers plot. Box shows quartile 1 to 3 and median; whiskers show quartile 1–1.5 of the interquartile range (IQR) and quartile 3 +1.5 the IQR. Circle; outlier >1.5 and <3 times the IQR. # = p<0.05. Figure 4 Data are shown as mean ± standard error

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Saccà, F., Puorro, G., Brunetti, A. et al. A randomized controlled pilot trial of lithium in spinocerebellar ataxia type 2.J Neurol 262, 149–153 (2015). https://doi.org/10.1007/s00415-014-7551-0

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