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Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS)

Al-Chalabi, A., Shaw, P.J., Young, C.A., Morrison, K.E., Murphy, C., Thornhill, M., Kelly, J., Steen, I.N. and Leigh, P.N. (2011) Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS). BMC Neurology, 11. Art no. 111. ISSN 1471-2377

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Abstract

Background: Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO(3) and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis.

Methods/Design: LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity >= 60% of predicted within 1 month prior to randomisation and age at least18 years.

Discussion: Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011.

Item Type: Article
Copyright, Publisher and Additional Information: © 2011 Al-Chalabi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: GLUTAMATE EXCITOTOXICITY; AXONAL-TRANSPORT; CORTICAL-NEURONS; CLINICAL-TRIALS; INHIBITION; AUTOPHAGY; DISEASE; GLYCOGEN-SYNTHASE-KINASE-3; Neuroprotection; Multicentre
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Department of Neuroscience (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 17 Nov 2011 16:21
Last Modified: 08 Feb 2013 17:35
Published Version: http://dx.doi.org/10.1186/1471-2377-11-111
Status: Published
Publisher: BioMed Central
Refereed: Yes
Identification Number: 10.1186/1471-2377-11-111
URI: http://eprints.whiterose.ac.uk/id/eprint/43432

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