title: Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].
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
  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.
  
  
  CONCLUSIONS
  Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011.
  
  
  BACKGROUND
  Current controlled trials ISRCTN83178718.
authors.affiliation: MRC Centre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, London SE5 8AF, UK. ammar.al-chalabi@kcl.ac.uk
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Young
authors.forename: Karen E
authors.initials: KE
authors.lastname: Morrison
authors.forename: Caroline
authors.initials: C
authors.lastname: Murphy
authors.forename: Marie
authors.initials: M
authors.lastname: Thornhill
authors.forename: Joanna
authors.initials: J
authors.lastname: Kelly
authors.forename: I Nicholas
authors.initials: IN
authors.lastname: Steen
authors.forename: P Nigel
authors.initials: PN
authors.lastname: Leigh
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality; D002985:Clinical Protocols; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D019782:Riluzole / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D018696:Neuroprotective Agents; D010919:Placebos; D016651:Lithium Carbonate; D019782:Riluzole