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Lithium Carbonate for patients with Amyotrophic Lateral Sclerosis
ISRCTN ISRCTN83178718
DOI 10.1186/ISRCTN83178718
ClinicalTrials.gov identifier
EudraCT number 2008-006891-31
Public title Lithium Carbonate for patients with Amyotrophic Lateral Sclerosis
Scientific title A double-blind randomised controlled trial of Lithium Carbonate in patients with Amyotrophic Lateral Sclerosis
Acronym LiCALS
Serial number at source RAA/2008/013
Study hypothesis Lithium carbonate, combined with standard amyotrophic lateral sclerosis (ALS) treatment, may prolong survival, slow the rate of functional deterioration and improve the quality of life and mental state of ALS patients, measured over 18 months.
Lay summary Not provided at time of registration
Ethics approval South East Research Ethics Committee gave approval on the 17th February 2009 (ref: 09/H1102/15)
Study design Multicentre double-blind randomised parallel group controlled trial
Countries of recruitment United Kingdom
Disease/condition/study domain Amyotrophic lateral sclerosis (ALS); also known as motor neurone disease (MND)
Participants - inclusion criteria 1. Patients with possible, laboratory-supported probable, probable or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria (The Airlie House Statement: http://www.wfnals.org). These criteria are internationally accepted research diagnostic criteria with high specificity and sensitivity. The onset form (bulbar or limb) and disease type (familial or sporadic) will be recorded; source documents will include a full report of an electromyogram (EMG) reported by an experienced neurophysiologist as compatible with ALS. The neurological exam should be performed by a physician.
2. Disease duration greater than or equal to 6 months and less than or equal to 36 calendar months (inclusive), with disease onset defined as date of first muscle weakness, or dysarthria
3. SVC greater than or equal to 60% of predicted within 1 month prior to randomisation
4. Aged greater than or equal to 18 years (inclusive), either sex
5. In the case of a female with childbearing potential, the patient must not be pregnant or breast-feeding. Women of childbearing potential will have a urine pregnancy test before randomisation and at each clinic visit. The results of those must be negative. Women of childbearing potential should use adequate contraception.
6. Continuously treated with riluzole for at least 4 weeks prior to screening (28 days inclusive) and stabilised at 100 mg/day (50 mg twice daily [bid]) without significant adverse drug reactions
7. Capable of understanding the information given and giving fully informed consent prior to any study specific procedures
Participants - exclusion criteria 1. Participation in another therapeutic study within the preceding 12 weeks or use of other investigational drugs or agents
2. Tracheostomy, or assisted ventilation of any type during the preceding three months
3. Existing gastrostomy, unless elective and not currently used for nutritional support or hydration
4. Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
5. Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment
6. Confirmed hepatic insufficiency or abnormal liver function (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] greater than 1.5 times the upper limit of the normal range) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the levels return to normal, the patient may then be included in the study.
7. Renal insufficiency (serum creatinine greater than upper limit of normal [ULN] for the centre/local laboratory) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the level returns to normal, the patient may then be included in the study.
8. Recorded diagnosis or evidence of major psychiatric disorder or clinically evident dementia
9. Known allergy or hypersensitivity to lithium, or its excipients
10. Likely to be uncooperative or to fail to comply with the trial requirements or to be inaccessible in the event of an emergency
11. Subjects with significant haematological, biochemical and autoimmune abnormalities, as judged by the study physician
12. If a woman of childbearing potential, unable or unwilling to use effective contraception during the study
13. Patients with active inflammation/infection at screening or baseline (day 0). Patients presenting with active inflammation/infection can be reassessed at a later date, and included in the trial if the infection/inflammation has cleared.
14. Patients already taking lithium in any form
15. Presence of a medical condition contra-indicative to the use of lithium, according to the British National Formulary (BNF) (http://www.bnf.org/bnf/)
Anticipated start date 01/05/2009
Anticipated end date 01/03/2012
Status of trial Completed
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 220
Interventions Lithium carbonate or matched placebo.

The dose will be titrated during the first 4 weeks of the trial (some patients may require a longer titration period) to achieve plasma lithium levels of 0.4 - 0.8 mmol/l. Tablets will be given orally once a day (in the evening). The tablets contain 295 mg of lithium carbonate or placebo - we anticipate that most patients will be on two tablets for the duration of the trial, following the titration phase. Some people may need three tablets or, in exceptional circumstances, four.

The total duration of treatment (and follow-up) is 18 months (77 weeks).
Primary outcome measure(s) Death from any cause at 18 months defined from the date of randomisation
Secondary outcome measure(s) 1. Slope of ALS Functional Rating Scale - Revised (ALSFRS-R) scores
2. Change in EuroQOL (EQ-5D)
3. Change in Hospital Anxiety and Depression Scale (HADS)

Collected at week 0 (baseline), week 12 (month 3), month 6, 9, 2, 15 and 18 (and withdrawal).
Sources of funding Motor Neurone Disease (MND) Association (UK) (ref: Leigh/Jul08/RF/6345)
Trial website
Publications 1. 2011 protocol in http://www.ncbi.nlm.nih.gov/pubmed/21936930
Contact name Prof  Peter N  Leigh
  Address Academic Neurosciences Centre
PO41 Institute of Psychiatry
King's College London
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
Sponsor King's College London (UK)
  Address PO01, Institute of Psychiatry
De Crespigny Park
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
  Sponsor website: http://www.iop.kcl.ac.uk/
Date applied 25/03/2009
Last edited 25/01/2012
Date ISRCTN assigned 08/05/2009
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