Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) Nervous System Diseases Amyotrophic Lateral Sclerosis
Conditions
Interventions
1000 patients (500 in each arm) will be recruited over twelve months.
All patients will be stabilised on riluzole 100 mg daily and be randomised to either of the following study groups:
1. 200 mg mi
Sponsors
King's College London (UK)
Eligibility
Inclusion criteria
Inclusion criteria: 1. Possible, probable (clinically or laboratory) 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/). 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 2. Disease duration more than 6 months (required by the El Escorial Criteria as the minimum time required to determine that there has been progression) and less than 5 years (inclusive); disease onset defined as date of first muscle weakness 3. Vital Capacity (VC) greater than or equal to 40 % of predicted 4. Age: greater than or equal to 18 years (inclusive) 5. Sex: male or female. In the case of a female with childbearing potential, the patient must use adequate contraceptive measures and must not be pregnant or breast-feeding 6. Continuously treated with riluzole for at least 3 months and stabilised at 100 mg/day (50 mg twice a day) without significant adverse drug reactions 7. Capable of understanding the information given and giving fully informed consent
Exclusion criteria
Exclusion criteria: 1. Previous participation in another clinical study within the preceding 12 weeks 2. Tracheostomy, assisted ventilation of any type during the preceding three months 3. Existing gastrostomy 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] and/or alanine aminotransferase [ALT] greater than 1.5 the upper limit of the normal range) 7. Renal insufficiency (serum creatinine greater than 200 µmol/L [2.26 mg/dL]) 8. Evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms 9. Known hypersensitivity to any component of the study drugs or to drugs in this class 10. Likely to be unco-operative or to fail to comply with the trial requirements or to be inaccessible in the event of an emergency 11. Unable or unwilling to use an effective method of contraception if a woman of childbearing age We have chosen inclusion criteria that are permissive (i.e., sensitive) without sacrificing specificity. The El Escorial Criteria of the World Federation of Neurology (The ?Airlie House Statement?: http://www.wfnals.org/) are internationally accepted research diagnostic criteria with high specificity and sensitivity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival (death alone) at 18 months. For the event rate, death alone will be used and ascertained through death certificates to achieve complete data for date. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ALS Functional Rating Scale, revised version (ALSFRS-R) 2. EuroQol EQ-5D 3. Client Service Receipt Inventory (CSRI), which will be specifically adapted for this study 4. Safety will be assessed through adverse event reports according to GCP standards required by the European Directive, and by haematological and biochemical analyses 5. Blood (1000 patients) and CSF (200 patients) will be collected for biomarkers of drug action and for pharmacokinetic and pharmacogenomic studies | — |
Countries
France, United Kingdom
Outcome results
None listed