title: Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS.
abstract: Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40-70 years of age, duration 6-24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient (p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% (p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) (p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) (p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) (p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed.
authors: Dipartimento di Neuroscienze, Istituto di Ricerche Farmacologiche Mario Negri, Via G. la Masa 19, Milan, Italy. ettore.beghi@marionegri.it
authors: Ettore
authors: E
authors: Beghi
authors: Elisabetta
authors: E
authors: Pupillo
authors: Virginio
authors: V
authors: Bonito
authors: Paolo
authors: P
authors: Buzzi
authors: Claudia
authors: C
authors: Caponnetto
authors: Adriano
authors: A
authors: Chiò
authors: Massimo
authors: M
authors: Corbo
authors: Fabio
authors: F
authors: Giannini
authors: Maurizio
authors: M
authors: Inghilleri
authors: Vincenzo La
authors: VL
authors: Bella
authors: Giancarlo
authors: G
authors: Logroscino
authors: Lorenzo
authors: L
authors: Lorusso
authors: Christian
authors: C
authors: Lunetta
authors: Letizia
authors: L
authors: Mazzini
authors: Paolo
authors: P
authors: Messina
authors: Gabriele
authors: G
authors: Mora
authors: Michele
authors: M
authors: Perini
authors: Maria Lidia
authors: ML
authors: Quadrelli
authors: Vincenzo
authors: V
authors: Silani
authors: Isabella L
authors: IL
authors: Simone
authors: Lucio
authors: L
authors: Tremolizzo
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D011788:Quality of Life; D019782:Riluzole / Q000627:therapeutic use; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D000108:Acetylcarnitine; D019782:Riluzole