Condition category
Nervous System Diseases
Date applied
26/02/2007
Date assigned
03/05/2007
Last edited
29/07/2009
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof P. Nigel Leigh

ORCID ID

Contact details

MRC Centre for Neurodegeneration Research
King’s College London
PO41 Academic Neuroscience Centre
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom

Additional identifiers

EudraCT number

2006-003992-11

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

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

Trial setting

Hospitals

Trial 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

Phase

Not Specified

Drug names

Minocycline

Primary outcome measures

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 trial start date

01/09/2007

Overall trial end date

31/03/2010

Reason abandoned

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

Patient

Age group

Not Specified

Gender

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

France, United Kingdom

Trial 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
United Kingdom

Sponsor type

University/education

Website

http://www.iop.kcl.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes