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| [ ...Back to search results ] | [ Print-friendly version ] |
| European trial of Minocycline IN Amyotrophic Lateral Sclerosis |
| Source of record | UK Clinical Trials Gateway |
| ISRCTN | ISRCTN72727460 |
| Date ISRCTN assigned | 03/05/2007 |
| Local reference number(s) | G0501266 |
| Public title | European trial of Minocycline IN Amyotrophic Lateral Sclerosis |
| Scientific title | |
| Acronym | EMINALS |
| Disease/condition/study domain | Amyotrophic Lateral Sclerosis (ALS)/ Motor Neuron Disease (MND) |
| Study hypothesis | Please note that as of 26/09/2007 this trial was stopped. The principal hypothesis is that minocycline will prove to be a clinically useful, cost-effective and safe disease-modifying (neuroprotective) treatment in Amyotrophic Lateral Sclerosis (ALS) by decreasing the rate of progression (reflected by improved survival at 18 months) and the rate of deterioration of function and Quality of Life (QL). In order to test the hypothesis that minocycline modifies Central Nervous System (CNS) cytokine production and/or pro-apoptotic pathways and that the changes observed can be related to CNS minocycline concentrations and drug response, we will collect blood and CerebroSpinal Fluid (CSF) samples from a sample of 200 patients (Institute of Psychiatry/ King's College London and Paris). We also wish to test the hypothesis that genetic variations in genes coding for cytokines (e.g. MCP-1) and drug efflux pump proteins influence response to minocycline therapy. We will therefore collect blood for DNA extraction from all patients in the trial. |
| Design/methodology | Multi-centre, international, double-blind, randomized, parallel group, stratified, controlled tiral. |
| Research ethics review | To be submitted as of 26 February 2007. |
| Countries of trial | United Kingdom and France |
| Participants - 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) ≥40 % of predicted 4. Age: ≥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 |
| Participants - 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 >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. |
| Patient information material | |
| Anticipated start date | 01/09/2007 |
| Anticipated end date | 31/03/2010 |
| Status of trial | Stopped |
| Target number of participants | 1000 |
| 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 randomized 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 measure(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 measure(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 |
| Sources of funding | Medical Research Council (UK) |
| Sponsor name | King's College London (UK) |
| Sponsor details | Institute of Psychiatry De Crespigny Park London United Kingdom SE5 8AF |
| Sponsor website | http://www.iop.kcl.ac.uk |
| Contact name | Prof P. Nigel Leigh |
| Contact details | MRC Centre for Neurodegeneration Research King¿s College London PO41 Academic Neuroscience Centre Institute of Psychiatry De Crespigny Park London United Kingdom SE5 8AF |
| More information | For more up-to-date information please go to the ISRCTN link below. |
| Link to record in ISRCTN Register | ISRCTN72727460 |
| Date last extracted from ISRCTN register | 17/04/2008 |
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