Lithium carbonate for patients with amyotrophic lateral sclerosis

ISRCTN	ISRCTN83178718
DOI	https://doi.org/10.1186/ISRCTN83178718
EudraCT/CTIS number	2008-006891-31
Secondary identifying numbers	RAA/2008/013

Submission date: 25/03/2009
Registration date: 08/05/2009
Last edited: 13/06/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Prof Peter N Leigh
Scientific

Academic Neurosciences Centre
PO41 Institute of Psychiatry
King's College London
London
SE5 8AF
United Kingdom

Study information

Study design	Multicentre double-blind randomised parallel-group controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A double-blind randomised controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis
Study acronym	LiCALS
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.
Ethics approval(s)	South East Research Ethics Committee, 17/02/2009, ref: 09/H1102/15
Condition	Amyotrophic lateral sclerosis (ALS); also known as motor neurone disease (MND)
Intervention	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 - it is anticipated 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).
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Lithium carbonate
Primary outcome measure	Death from any cause at 18 months defined from the date of randomisation
Secondary outcome measures	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) Measured at week 0 (baseline), week 12 (month 3), month 6, 9, 2, 15 and 18 (and withdrawal).
Overall study start date	01/05/2009
Overall study end date	01/03/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	220
Participant 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
Participant 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/)
Recruitment start date	01/05/2009
Recruitment end date	01/03/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

King's College London

London
SE5 8AF
United Kingdom

Sponsor information

King's College London (UK)
University/education

PO01, Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
England
United Kingdom

Website	http://www.iop.kcl.ac.uk/
"ROR"	https://ror.org/0220mzb33

Funders

Funder type

Charity

Motor Neurone Disease (MND) Association (UK) (ref: Leigh/Jul08/RF/6345)
Private sector organisation / Associations and societies (private and public)

Alternative name(s): MND Association, MNDA
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	21/09/2011		Yes	No
Results article	results	01/04/2013		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

13/06/2017: Publication reference added.