Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS

Ettore Beghi, Elisabetta Pupillo, Virginio Bonito, Paolo Buzzi, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Fabio Giannini, Maurizio Inghilleri, Vincenzo La Bella, Giancarlo Logroscino, Lorenzo Lorusso, Christian Lunetta, Letizia Mazzini, Paolo Messina, Gabriele Mora, Michele Perini, Maria Lidia Quadrelli, Vincenzo Silani, Isabella L. SimoneLucio Tremolizzo, Vito Samarelli, Rosanna Tortelli, Eustachio D'Errico, Maria Merello, Fiorella Tavernelli, Giovanni L. Mancardi, Maria Mascolo, Caterina Bendotti, Mariagrazia Buratti, Irene Floriani, Laura Giordano, Giorgia Giussani, Luca Maderna, Eleonora Maestri, Kalliopi Marinou, Tiziana Mennini, Stefano Messina, Cludia Morelli, Laura Papetti, Aurora Rizzo, Nicola Ticozzi, Federico Verde, Carlo Ferrarese, Laura Marzorati, Lucia Testa, Francesca Valentino, Vittorio Frasca, Elena Giacomelli, Stefania Casa, Maria Malentacchi, Andrea Calvo, Stefania Cammarosano, Cristina Moglia, Enrico Cavallo, Giuseppe Fuda

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)397-405
Number of pages9
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume14
Issue number5-6
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Acetylcarnitine
Amyotrophic Lateral Sclerosis
Placebos
Vital Capacity
Riluzole
Quality of Life
Deglutition
Population
Food
Survival
Mortality
Pharmaceutical Preparations

Keywords

  • Acetyl-L-carnitine
  • Amyotrophic lateral sclerosis
  • Motor neuron disease
  • Randomized trial

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS. / Beghi, Ettore; Pupillo, Elisabetta; Bonito, Virginio; Buzzi, Paolo; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Giannini, Fabio; Inghilleri, Maurizio; Bella, Vincenzo La; Logroscino, Giancarlo; Lorusso, Lorenzo; Lunetta, Christian; Mazzini, Letizia; Messina, Paolo; Mora, Gabriele; Perini, Michele; Quadrelli, Maria Lidia; Silani, Vincenzo; Simone, Isabella L.; Tremolizzo, Lucio; Samarelli, Vito; Tortelli, Rosanna; D'Errico, Eustachio; Merello, Maria; Tavernelli, Fiorella; Mancardi, Giovanni L.; Mascolo, Maria; Bendotti, Caterina; Buratti, Mariagrazia; Floriani, Irene; Giordano, Laura; Giussani, Giorgia; Maderna, Luca; Maestri, Eleonora; Marinou, Kalliopi; Mennini, Tiziana; Messina, Stefano; Morelli, Cludia; Papetti, Laura; Rizzo, Aurora; Ticozzi, Nicola; Verde, Federico; Ferrarese, Carlo; Marzorati, Laura; Testa, Lucia; Valentino, Francesca; Frasca, Vittorio; Giacomelli, Elena; Casa, Stefania; Malentacchi, Maria; Calvo, Andrea; Cammarosano, Stefania; Moglia, Cristina; Cavallo, Enrico; Fuda, Giuseppe.

In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Vol. 14, No. 5-6, 09.2013, p. 397-405.

Research output: Contribution to journalArticle

Beghi, E, Pupillo, E, Bonito, V, Buzzi, P, Caponnetto, C, Chiò, A, Corbo, M, Giannini, F, Inghilleri, M, Bella, VL, Logroscino, G, Lorusso, L, Lunetta, C, Mazzini, L, Messina, P, Mora, G, Perini, M, Quadrelli, ML, Silani, V, Simone, IL, Tremolizzo, L, Samarelli, V, Tortelli, R, D'Errico, E, Merello, M, Tavernelli, F, Mancardi, GL, Mascolo, M, Bendotti, C, Buratti, M, Floriani, I, Giordano, L, Giussani, G, Maderna, L, Maestri, E, Marinou, K, Mennini, T, Messina, S, Morelli, C, Papetti, L, Rizzo, A, Ticozzi, N, Verde, F, Ferrarese, C, Marzorati, L, Testa, L, Valentino, F, Frasca, V, Giacomelli, E, Casa, S, Malentacchi, M, Calvo, A, Cammarosano, S, Moglia, C, Cavallo, E & Fuda, G 2013, 'Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS', Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol. 14, no. 5-6, pp. 397-405. https://doi.org/10.3109/21678421.2013.764568
Beghi, Ettore ; Pupillo, Elisabetta ; Bonito, Virginio ; Buzzi, Paolo ; Caponnetto, Claudia ; Chiò, Adriano ; Corbo, Massimo ; Giannini, Fabio ; Inghilleri, Maurizio ; Bella, Vincenzo La ; Logroscino, Giancarlo ; Lorusso, Lorenzo ; Lunetta, Christian ; Mazzini, Letizia ; Messina, Paolo ; Mora, Gabriele ; Perini, Michele ; Quadrelli, Maria Lidia ; Silani, Vincenzo ; Simone, Isabella L. ; Tremolizzo, Lucio ; Samarelli, Vito ; Tortelli, Rosanna ; D'Errico, Eustachio ; Merello, Maria ; Tavernelli, Fiorella ; Mancardi, Giovanni L. ; Mascolo, Maria ; Bendotti, Caterina ; Buratti, Mariagrazia ; Floriani, Irene ; Giordano, Laura ; Giussani, Giorgia ; Maderna, Luca ; Maestri, Eleonora ; Marinou, Kalliopi ; Mennini, Tiziana ; Messina, Stefano ; Morelli, Cludia ; Papetti, Laura ; Rizzo, Aurora ; Ticozzi, Nicola ; Verde, Federico ; Ferrarese, Carlo ; Marzorati, Laura ; Testa, Lucia ; Valentino, Francesca ; Frasca, Vittorio ; Giacomelli, Elena ; Casa, Stefania ; Malentacchi, Maria ; Calvo, Andrea ; Cammarosano, Stefania ; Moglia, Cristina ; Cavallo, Enrico ; Fuda, Giuseppe. / Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS. In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2013 ; Vol. 14, No. 5-6. pp. 397-405.
@article{8835c1b0ce3d4420bce7ca141a02ab04,
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.",
keywords = "Acetyl-L-carnitine, Amyotrophic lateral sclerosis, Motor neuron disease, Randomized trial",
author = "Ettore Beghi and Elisabetta Pupillo and Virginio Bonito and Paolo Buzzi and Claudia Caponnetto and Adriano Chi{\`o} and Massimo Corbo and Fabio Giannini and Maurizio Inghilleri and Bella, {Vincenzo La} and Giancarlo Logroscino and Lorenzo Lorusso and Christian Lunetta and Letizia Mazzini and Paolo Messina and Gabriele Mora and Michele Perini and Quadrelli, {Maria Lidia} and Vincenzo Silani and Simone, {Isabella L.} and Lucio Tremolizzo and Vito Samarelli and Rosanna Tortelli and Eustachio D'Errico and Maria Merello and Fiorella Tavernelli and Mancardi, {Giovanni L.} and Maria Mascolo and Caterina Bendotti and Mariagrazia Buratti and Irene Floriani and Laura Giordano and Giorgia Giussani and Luca Maderna and Eleonora Maestri and Kalliopi Marinou and Tiziana Mennini and Stefano Messina and Cludia Morelli and Laura Papetti and Aurora Rizzo and Nicola Ticozzi and Federico Verde and Carlo Ferrarese and Laura Marzorati and Lucia Testa and Francesca Valentino and Vittorio Frasca and Elena Giacomelli and Stefania Casa and Maria Malentacchi and Andrea Calvo and Stefania Cammarosano and Cristina Moglia and Enrico Cavallo and Giuseppe Fuda",
year = "2013",
month = "9",
doi = "10.3109/21678421.2013.764568",
language = "English",
volume = "14",
pages = "397--405",
journal = "Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration",
issn = "2167-8421",
publisher = "Informa Healthcare",
number = "5-6",

}

TY - JOUR

T1 - Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS

AU - Beghi, Ettore

AU - Pupillo, Elisabetta

AU - Bonito, Virginio

AU - Buzzi, Paolo

AU - Caponnetto, Claudia

AU - Chiò, Adriano

AU - Corbo, Massimo

AU - Giannini, Fabio

AU - Inghilleri, Maurizio

AU - Bella, Vincenzo La

AU - Logroscino, Giancarlo

AU - Lorusso, Lorenzo

AU - Lunetta, Christian

AU - Mazzini, Letizia

AU - Messina, Paolo

AU - Mora, Gabriele

AU - Perini, Michele

AU - Quadrelli, Maria Lidia

AU - Silani, Vincenzo

AU - Simone, Isabella L.

AU - Tremolizzo, Lucio

AU - Samarelli, Vito

AU - Tortelli, Rosanna

AU - D'Errico, Eustachio

AU - Merello, Maria

AU - Tavernelli, Fiorella

AU - Mancardi, Giovanni L.

AU - Mascolo, Maria

AU - Bendotti, Caterina

AU - Buratti, Mariagrazia

AU - Floriani, Irene

AU - Giordano, Laura

AU - Giussani, Giorgia

AU - Maderna, Luca

AU - Maestri, Eleonora

AU - Marinou, Kalliopi

AU - Mennini, Tiziana

AU - Messina, Stefano

AU - Morelli, Cludia

AU - Papetti, Laura

AU - Rizzo, Aurora

AU - Ticozzi, Nicola

AU - Verde, Federico

AU - Ferrarese, Carlo

AU - Marzorati, Laura

AU - Testa, Lucia

AU - Valentino, Francesca

AU - Frasca, Vittorio

AU - Giacomelli, Elena

AU - Casa, Stefania

AU - Malentacchi, Maria

AU - Calvo, Andrea

AU - Cammarosano, Stefania

AU - Moglia, Cristina

AU - Cavallo, Enrico

AU - Fuda, Giuseppe

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Acetyl-L-carnitine

KW - Amyotrophic lateral sclerosis

KW - Motor neuron disease

KW - Randomized trial

UR - http://www.scopus.com/inward/record.url?scp=84881322666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881322666&partnerID=8YFLogxK

U2 - 10.3109/21678421.2013.764568

DO - 10.3109/21678421.2013.764568

M3 - Article

C2 - 23421600

AN - SCOPUS:84881322666

VL - 14

SP - 397

EP - 405

JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

SN - 2167-8421

IS - 5-6

ER -