Lithium carbonate in amyotrophic lateral sclerosis Lack of efficacy in a dose-finding trial

被引：80

作者：

Chio, A. ^{[1
,2
]}

Borghero, G. ^{[3
,4
]}

Calvo, A. ^{[1
,2
]}

Capasso, M. ^{[5
]}

Caponnetto, C. ^{[6
]}

Corbo, M. ^{[7
]}

Giannini, F. ^{[8
]}

Logroscino, G. ^{[9
,10
]}

Mandrioli, J. ^{[11
,12
]}

Marcello, N. ^{[13
]}

Mazzini, L. ^{[14
]}

Moglia, C. ^{[1
,2
]}

Monsurro, M. R. ^{[15
]}

Mora, G. ^{[16
]}

Patti, F. ^{[17
]}

Perini, M.

Pietrini, V. ^{[18
,19
]}

Pisano, F. ^{[20
]}

Pupillo, E. ^{[21
]}

Sabatelli, M. ^{[22
]}

Salvi, F. ^{[23
]}

Silani, V. ^{[24
,25
]}

Simone, I. L. ^{[9
,10
]}

Soraru, G. ^{[26
]}

Tola, M. R. ^{[28
]}

Volanti, P. ^{[27
]}

Beghi, E. ^{[21
]}

机构：

[1] AOU San Giovanni Battista, Dept Neurosci, I-10126 Turin, Italy

[2] Univ Turin, Turin, Italy

[3] AOU Cagliari, Cagliari, Italy

[4] Univ Cagliari, Cagliari, Italy

[5] Univ GAnnunzio Chieti, Ctr Reg Malattie Neuromuscolari, Chieti, Italy

[6] Univ Genoa, Neurol Clin 2, Genoa, Italy

[7] AO Niguarda Ca Granda, Fdn Serena, NEMO, Milan, Italy

[8] Univ Siena, Dipartimento Neurosci, Sez Neurol, I-53100 Siena, Italy

[9] Univ Bari, Clin Neurol Amaducci, Dipartimento Sci Neurol & Psichiatr, Bari, Italy

[10] Osped Consorziale Policlin, Bari, Italy

[11] Nuovo Osped Civile S Agostino Estense, Dipartimento Neurosci, Modena, Italy

[12] Univ Modena, I-41100 Modena, Italy

[13] ASO Arcispedale S Maria Nuova, UO Neurol, Reggio Emilia, Italy

[14] Univ Piemonte Orientale, ASO Osped Maggiore Novara, UO Neurol, Novara, Italy

[15] Univ Naples 2, Dipartimento Sci Neurol, Naples, Italy

[16] Fdn Salvatore Maugeri, IRCCS, SC Neuroriabilitaz, Milan, Italy

[17] Univ Catania, Ctr Sclerosi Multipla, Dipartimento Neurosci, I-95124 Catania, Italy

[18] AOU Parma, Sez Neurol, Dipartimento Neurosci, Parma, Italy

[19] Univ Parma, I-43100 Parma, Italy

[20] Fdn Salvatore Maugeri, IRCCS, Div Neurol Riabilitavia, Veruno, Italy

[21] Ist Farmacol Mario Negri, Dipartimento Neurosci, Milan, Italy

[22] Univ Cattolica Sacro Cuore, SC Neurol, Rome, Italy

[23] Osped Bellaria, Dipartimento Neurol, Ctr Diagnosi & Cura Malattie Rare, Bologna, Italy

[24] Univ Milan, Ist Auxol Italiano, Neurosci Lab, Ctr Dino Ferrari,IRCCS, I-20122 Milan, Italy

[25] Univ Milan, Ist Auxol Italiano, IRCCS, UO Neurol, I-20122 Milan, Italy

[26] Univ Padua, Dipartimento Neurosci, UO Neuropatol & Psicopatol, Padua, Italy

[27] Fdn Salvatore Maugeri, IRCCS, SC Neuroriabilitaz, Mistretta, Italy

[28] AOU S Anna Ferrara, UO Neurol, Dipartimento Neurosci Riabilitaz, Ferrara, Italy

来源：

NEUROLOGY | 2010年 / 75卷 / 07期

关键词：

DISEASE PROGRESSION; MOUSE MODEL; ALS; SURVIVAL;

D O I：

10.1212/WNL.0b013e3181ed9e7c

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. Neurology (R) 2010; 75: 619-625

引用

页码：619 / 625

页数：7

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