PMID- 20702794 OWN - NLM STAT- MEDLINE DCOM- 20100913 LR - 20140730 IS - 1526-632X (Electronic) IS - 0028-3878 (Linking) VI - 75 IP - 7 DP - 2010 Aug 17 TI - Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial. PG - 619-25 LID - 10.1212/WNL.0b013e3181ed9e7c [doi] AB - BACKGROUND: A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). METHODS: The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs (http://oss-sper-clin.agenziafarmaco.it/) (EudraCT number 2008-001094-15). RESULTS: As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. CONCLUSIONS: Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs. FAU - Chio, A AU - Chio A AD - Department of Neuroscience, via Cherasco 15, 10126 Torino, Italy. achio@usa.net FAU - Borghero, G AU - Borghero G FAU - Calvo, A AU - Calvo A FAU - Capasso, M AU - Capasso M FAU - Caponnetto, C AU - Caponnetto C FAU - Corbo, M AU - Corbo M FAU - Giannini, F AU - Giannini F FAU - Logroscino, G AU - Logroscino G FAU - Mandrioli, J AU - Mandrioli J FAU - Marcello, N AU - Marcello N FAU - Mazzini, L AU - Mazzini L FAU - Moglia, C AU - Moglia C FAU - Monsurro, M R AU - Monsurro MR FAU - Mora, G AU - Mora G FAU - Patti, F AU - Patti F FAU - Perini, M AU - Perini M FAU - Pietrini, V AU - Pietrini V FAU - Pisano, F AU - Pisano F FAU - Pupillo, E AU - Pupillo E FAU - Sabatelli, M AU - Sabatelli M FAU - Salvi, F AU - Salvi F FAU - Silani, V AU - Silani V FAU - Simone, I L AU - Simone IL FAU - Soraru, G AU - Soraru G FAU - Tola, M R AU - Tola MR FAU - Volanti, P AU - Volanti P FAU - Beghi, E AU - Beghi E CN - LITALS Study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20100811 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Enzyme Inhibitors) RN - 2BMD2GNA4V (Lithium Carbonate) SB - IM CIN - Neurology. 2010 Aug 17;75(7):586-7. PMID: 20702793 MH - Adolescent MH - Adult MH - Aged MH - Amyotrophic Lateral Sclerosis/blood/*drug therapy/mortality MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/blood/*therapeutic use MH - Female MH - Follow-Up Studies MH - Humans MH - Kaplan-Meier Estimate MH - Lithium Carbonate/blood/*therapeutic use MH - Male MH - Middle Aged MH - Retrospective Studies MH - Single-Blind Method MH - Time Factors MH - Treatment Outcome MH - Young Adult FIR - Tortelli, R IR - Tortelli R FIR - D'Errico, E IR - D'Errico E FIR - Bartolomei, I IR - Bartolomei I FIR - Barbarossa, E IR - Barbarossa E FIR - Depau, B IR - Depau B FIR - Costantino, E IR - Costantino E FIR - D'Amico, E IR - D'Amico E FIR - Uncini, A IR - Uncini A FIR - Manzoli, C IR - Manzoli C FIR - Quatrale, R IR - Quatrale R FIR - Sette, E IR - Sette E FIR - Montanari, E IR - Montanari E FIR - Merello, M IR - Merello M FIR - Zarcone, D IR - Zarcone D FIR - Mascolo, M IR - Mascolo M FIR - Vignolo, M IR - Vignolo M FIR - Messina, S IR - Messina S FIR - Morelli, C IR - Morelli C FIR - Marinou, K IR - Marinou K FIR - Papetti, L IR - Papetti L FIR - Lunetta, C IR - Lunetta C FIR - Gorni, K IR - Gorni K FIR - De Cicco, D IR - De Cicco D FIR - Pipia, C IR - Pipia C FIR - Sola, P IR - Sola P FIR - Georgoulopoulou, E IR - Georgoulopoulou E FIR - Sagnelli, A IR - Sagnelli A FIR - Tedeschi, G IR - Tedeschi G FIR - Oggioni, G IR - Oggioni G FIR - Nasuelli, N IR - Nasuelli N FIR - D'Ascenzo, C IR - D'Ascenzo C FIR - Cima, V IR - Cima V FIR - Aiello, M IR - Aiello M FIR - Rizzi, R IR - Rizzi R FIR - Rinaldi, E IR - Rinaldi E FIR - Luigetti, M IR - Luigetti M FIR - Conte, A IR - Conte A FIR - Torzini, A IR - Torzini A FIR - Greco, G IR - Greco G FIR - Mutani, R IR - Mutani R FIR - Fuda, G IR - Fuda G FIR - Tommasi, M A IR - Tommasi MA EDAT- 2010/08/13 06:00 MHDA- 2010/09/14 06:00 CRDT- 2010/08/13 06:00 PHST- 2010/08/13 06:00 [entrez] PHST- 2010/08/13 06:00 [pubmed] PHST- 2010/09/14 06:00 [medline] AID - WNL.0b013e3181ed9e7c [pii] AID - 10.1212/WNL.0b013e3181ed9e7c [doi] PST - ppublish SO - Neurology. 2010 Aug 17;75(7):619-25. doi: 10.1212/WNL.0b013e3181ed9e7c. Epub 2010 Aug 11.