European trial of Minocycline IN Amyotrophic Lateral Sclerosis

INTERVENTION: 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 minocycline daily as capsules containing 50 mg base of minocycline, four to be taken in the morning, with subject upright, for 18 months 2. Matching placebo, 18 months This trial is sponsored jointly by King's College London (UK) and Assistance Publique Hopitaux de Paris (France). CONDITION: Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) ; Nervous System Diseases ; Amyotrophic Lateral Sclerosis PRIMARY OUTCOME: 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 OUTCOME: 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 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‐