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Open Access Study protocol

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31]

Ammar Al-Chalabi1*, Pamela J Shaw2, Carolyn A Young3, Karen E Morrison4, Caroline Murphy5, Marie Thornhill1, Joanna Kelly5, I Nicholas Steen6, P Nigel Leigh17 and on behalf of UKMND-LiCALS

Author affiliations

1 MRC Centre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, London SE5 8AF, UK

2 Academic Neurology Unit, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK

3 Walton Centre for Neurology & Neurosurgery, Lower Lane, Liverpool L9 7LJ, UK

4 College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK

5 Mental Health and Neuroscience Clinical Trials Unit, King's College London, Institute of Psychiatry, London SE5 8AF, UK

6 Institute of Health and Society, University of Newcastle upon Tyne, 21 Claremont Place, Newcastle upon Tyne, NE2 4AA, UK

7 Brighton and Sussex Medical School, Trafford Centre for Biomedical Research, University of Sussex, Falmer, East Sussex BN1 9RY, UK

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Citation and License

BMC Neurology 2011, 11:111  doi:10.1186/1471-2377-11-111

Published: 21 September 2011

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 LiCO3 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.

Trial registration

Current controlled trials ISRCTN83178718