The aim of our study was to test the safety and tolerability of lithium in multiple system atrophy (MSA). The study was randomized, placebo-controlled, and double-blind. The primary endpoint of the study was safety and tolerability. An interim analysis, performed 1 year after the first patient was randomized, showed a higher proportion of trial abandon (P < 0.01) and a higher number of adverse events (P < 0.02) in the lithium group. The trial was stopped by the Data Monitoring Committee. Overall, lithium was not well tolerated, and we do not encourage future studies with lithium in MSA patients.
Lithium Multiple system atrophy Clinical trial Safety Phase II
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The study was supported by Associazione Italiana per la lotta alle Sindromi Atassiche (AISA) sez. Campania. We are grateful to 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. We thank the patients and their families for their willingness to take part to this research project.
Conflicts of interest
The authors report no competing interests.
All human studies must state that they have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Quinn N (1989) Multiple system atrophy—the nature of the beast. J Neurol Neurosurg Psychiatry (suppl):78–89Google Scholar
Sarkar S, Floto RA, Berger Z et al (2005) Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol 170:1101–1111PubMedCrossRefGoogle Scholar
Webb JL, Ravikumar B, Atkins J et al (2003) Alpha-synuclein is degraded by both autophagy and the proteasome. J Biol Chem 278:25009–25013PubMedCrossRefGoogle Scholar
Sarkar S, Krishna G, Imarisio S et al (2008) A rational mechanism for combination treatment of Huntington’s disease using lithium and rapamycin. Hum Mol Genet 17:170–178PubMedCrossRefGoogle Scholar
Verstraete E, Veldink JH, Huisman MH et al (2012) Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial. J Neurol Neurosurg Psychiatry 83:557–564PubMedCrossRefGoogle Scholar
Al-Chalabi A, Shaw PJ, Young CA et al (2011) Protocol for a double-blind randomized placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) (Eudract number: 2008-006891-31). BMC Neurol 11:111PubMedCrossRefGoogle Scholar
Miller RG, Moore DH, Forshew DA et al (2011) Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design. Neurology 77:973–979PubMedCrossRefGoogle Scholar
Aggarwal SP, Zinman L, Simpson E et al (2010) Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 9:481–488PubMedCrossRefGoogle Scholar
Forlenza OV, Diniz BS, Radanovic M et al (2011) Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 198:351–356PubMedCrossRefGoogle Scholar
Wenning GK, Tison F, Seppi K et al (2004) Development and validation of the unified multiple system atrophy rating scale (UMSARS). Mov Disord 19:1391–1402PubMedCrossRefGoogle Scholar
Beck AT, Steer RA, Brown GK et al (1996) BDI-II—beck depression inventory, 2nd edn. The Psychological Corporation Harcourt Brace and Company, San AntonioGoogle Scholar
Gilman S, Wenning GK, Low PA et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676PubMedCrossRefGoogle Scholar
Holmberg B, Johansson JO, Poewe W, Growth-Hormone MSA Study Group; European MSA Study Group et al (2007) Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study. Mov Disord 22:1138–1144PubMedCrossRefGoogle Scholar
Dodel R, Spottke A, Gerhard A et al (2010) Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11) C] (R)-PK11195 PET (MEMSA-trial). Mov Disord 25:97–107PubMedCrossRefGoogle Scholar