European trial of Minocycline IN Amyotrophic Lateral Sclerosis

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN72727460
• Date of registration: 03/05/2007
• Prospective Registration: Yes
• Primary sponsor: King's College London (UK)
• Public title: European trial of Minocycline IN Amyotrophic Lateral Sclerosis
• Date of first enrolment: 01/09/2007
• Target sample size: 1000
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN72727460
• Study type: Interventional
• Study design: Multi-centre international double-blind randomized, parallel group stratified controlled trial (Treatment)

Countries of recruitment

France, United Kingdom

Contacts

• Name: P. Nigel Leigh

Key inclusion & exclusion 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: 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.

Age minimum:
Age maximum:
Gender: Not Specified

Health Condition(s) or Problem(s) studied

Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
Nervous System Diseases
Amyotrophic Lateral Sclerosis

Intervention(s)

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).

Primary Outcome(s)

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(s)

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

Secondary ID(s)

2006-003992-11

G0501266

Source(s) of Monetary Support

Medical Research Council (MRC) (UK)