title: A randomized controlled pilot trial of lithium in spinocerebellar ataxia type 2.
abstract: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder. Lithium is able to stimulate autophagy, and to reduce Ca(2+) 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.
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II, Via Pansini, 5, 80131, Napoli, NA, Italy, francesco.sacca@unina.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccà
authors.forename: Giorgia
authors.initials: G
authors.lastname: Puorro
authors.forename: Arturo
authors.initials: A
authors.lastname: Brunetti
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.forename: Amedeo
authors.initials: A
authors.lastname: Cervo
authors.forename: Sirio
authors.initials: S
authors.lastname: Cocozza
authors.forename: Mariafulvia
authors.initials: M
authors.lastname: de Leva
authors.forename: Angela
authors.initials: A
authors.lastname: Marsili
authors.forename: Chiara
authors.initials: C
authors.lastname: Pane
authors.forename: Mario
authors.initials: M
authors.lastname: Quarantelli
authors.forename: Cinzia Valeria
authors.initials: CV
authors.lastname: Russo
authors.forename: Francesco
authors.initials: F
authors.lastname: Trepiccione
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Vincenzo Brescia
authors.initials: VB
authors.lastname: Morra
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001343:Autophagy / Q000187:drug effects; D001921:Brain / Q000473:pathology*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D016651:Lithium Carbonate