ithium carbonate for patients with amyotrophic lateral sclerosis

Phase 4

Completed

• Conditions: Amyotrophic lateral sclerosis (ALS); also known as motor neurone disease (MND); Nervous System Diseases; Spinal muscular atrophy and related syndromes

• Registration Number: ISRCTN83178718
• Lead Sponsor: King's College London (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-08
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 220

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

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/)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Death from any cause at 18 months defined from the date of randomisation

Secondary Outcome Measures

Name	Time	Method
1. Slope of ALS Functional Rating Scale - Revised (ALSFRS-R) scores<br>2. Change in EuroQOL (EQ-5D)<br>3. Change in Hospital Anxiety and Depression Scale (HADS)<br><br>Measured at week 0 (baseline), week 12 (month 3), month 6, 9, 2, 15 and 18 (and withdrawal).