Double-Blind Placebo-Controlled Trial on the Use of Acetyl-L-Carnitine for the Treatment of Amyotrophic Lateral Sclerosis (P04.151)

Objective: To assess superiority of acetyl-L-carnitine/riluzole (ALC) combination over riluzole alone on functional disability in patients with amyotrophic lateral sclerosis (ALS). Background ALS is a fatal motorneuron disease. Unlike riluzole, no disease-modifier drugs are available. ALC counteracts motor neuron death induced by toxic agents or deprivation of trophic factors and reduces disease progression in animal models. Design/Methods: Patients 40-70 years with definite or probable ALS, disease duration 6-24 months, self-supporting (ie, able to swallow, cut foods/handling utensils, and walk), and with forced vital capacity (FVC)>80% were enrolled in a pilot double-blind, placebo-controlled, parallel group trial and followed for 48 weeks. ALC 3g/day and placebo were added to riluzole 100mg/day. Primary end-point: no. patients becoming non self-supporting. Secondary end-points: changes in the ALS-FRS-R scale, MRC scale, FVC and McGill quality-of-life scale. Analysis was performed in the intention-to-treat (ITT) population, completers and completers/ compliers (ie, taking >75% of study drug). Results: 42 patients received ALC and 40 patients placebo. In the ITT population, 34 patients receiving ALC (80.9%) and 39 receiving placebo (97.5%) became non self-supporting (p=0.030). Percentages in study completers were 71.4 vs. 94.7% (p=0.064) and in "completers/compliers", 71.4% vs. 94.4% (p=0.069). In the per-protocol analysis, percentages were 84.4 vs. 100.0% (p=0.054) and 76.2 vs. 100.0% (p=0.132)(completers & completers/compliers). At 48 weeks, ALC was associated with higher mean ALR-FRS-R scores (p=0.039) and FVC scores (p=0.016), while MRC and quality of life were no different. Adverse events were similar. Conclusions: ALC appears superior to placebo and is well-tolerated and safe. A confirmatory phase III trial is needed. (*) Italian ALS Study Group: Virginio Bonito, Paolo Buzzi, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Fabio Giannini, Maurizio Inghilleri, Vincenzo La Bella, Lorenzo Lorusso, Christian Lunetta, Letizia Mazzini, Paolo Messina, Gabriele Mora, Michele Perini, Elisabetta Pupillo, Maria Lidia Quadrelli, Vincenzo Silani, Isabella Simone, Lucio Tremolizzo