Additional identifiers
EudraCT/CTIS number
2006-003992-11
IRAS number
ClinicalTrials.gov number
Protocol/serial number
G0501266
Study information
Scientific title
Acronym
EMINALS
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.
Ethics approval(s)
Not provided at time of registration
Study design
Multi-centre international double-blind randomized, parallel group stratified controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Condition
Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
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).
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Specified
Drug/device/biological/vaccine name(s)
Minocycline
Primary outcome measure
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 measures
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
Overall study start date
01/09/2007
Overall study end date
31/03/2010
Reason abandoned (if study stopped)
During the set up phase, new information emerged (a similar negative finding trial in the US) that meant the investigators have had to re-think the study completely and in essence, the study as it was registered cannot happen.
Eligibility
Participant 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
Participant type(s)
Patient
Age group
Not Specified
Lower age limit
18 Years
Sex
Not Specified
Target number of participants
1000
Participant 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.
Recruitment start date
01/09/2007
Recruitment end date
31/03/2010
Locations
Countries of recruitment
England, France, United Kingdom
Study participating centre
MRC Centre for Neurodegeneration Research
London
SE5 8AF
United Kingdom
Sponsor information
Organisation
King's College London (UK)
Sponsor details
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
England
United Kingdom
Sponsor type
University/education
Website
ROR
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK)
Alternative name(s)
UK Medical Research Council, MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|