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.

Key words::

• Acetyl-L-carnitine
• amyotrophic lateral sclerosis
• motor neuron disease
• randomized trial

Acknowledgements

The study was funded by Agenzia-Italiana-del- Farmaco (FARM5RLKR9). Sigma-Tau provided ALC and placebo free of charge. The authors are indebted to Susanna Franceschi and Stefania Moia for secretarial assistance. The study was also carried out on behalf of the ‘Fondazione Aldo & Cele Daccò per la Ricerca Scientifica’ and the European Union, grant agreement 259867. The manuscript was edited by J. D. Baggott.

Disclosure of interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. E. Beghi serves on the editorial advisory boards of Epilepsia, Amyotrophic Lateral Sclerosis, Clinical Neurology & Neurosurgery, and Neuroepidemiology; he has received funding for travel and speaker honoraria from UCB-Pharma, Sanofi-Aventis, GSK, EISAI; funding from GSK for educational presentations, and from AIFA, Sanofi-Aventis, Janssen-Cilag, EISAI, Lombardy Region, Istituto Superiore di Sanità and American ALS Association for the coordinating activity of RCT and observational study protocol. F. Giannini received funding from Kedrion SpA. V. La Bella received funding from the ‘Mario Negri’ Institute for pharmacological research, for patient recruitment and follow-up.

L. Mazzini received funding from the ‘Mario Negri’ Institute for pharmacological research and writing assistance. P. Messina has received funding from AIFA, Sanofi-Aventis, Janssen-Cilag, EISAI, Lombardy Region, Istituto Superiore di Sanità and American ALS Association for the data analysis and data management of RCT and observational study protocol. E. Pupillo has received funding from AIFA, Italian Ministry of Health, Istituto Superiore di Sanità, American ALS Association for data management and data monitoring of RCT and observational study protocol.

V. Silani received funding from BIOGEN for ALS Clinical Trial. A. Chiò received funding from BIOGEN Idec. I. L. Simone has received funding from Sanofi-Aventis as personal honoraria for educational lectures.

The authors alone are responsible for the content and writing of the paper.

The study was funded by Agenzia-Italiana-del-Farmaco (FARM5RLKR9). Sigma-Tau provided ALC and placebo free of charge.