Condition category
Eye Diseases
Date applied
03/05/2013
Date assigned
03/05/2013
Last edited
03/05/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Matthew Craner

ORCID ID

Contact details

Dept of Clinical Neurology
Level 6
West wing

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
matthew.craner@ndcn.ox.ac.uk

Additional identifiers

EudraCT number

2012-004980-39

ClinicalTrials.gov number

NCT01802489

Protocol/serial number

13895

Study information

Scientific title

Acronym

ACTION

Study hypothesis

Multiple sclerosis (MS), an inflammatory condition of the nervous system, is the most common cause of disability in people of working age in the western world. MS can cause loss of nerve cells, and this loss of nerve cells is closely linked to the amount of disability caused by MS.

Optic neuritis (ON) is a common event in MS, and causes significant loss of nerve cells in the eye, resulting in poor vision. ON also provides a sensitive way of testing the effectiveness of drugs that may help protect from loss of nerve cells in ON and therefore in MS.

We have identified through laboratory and early clinical research in humans that amiloride (a water tablet already used in the UK) may be a drug that can be of benefit in ON by protecting from loss of nerves cells (a neuroprotective drug). We propose a combination of simple eye scanning techniques along with magnetic resonance imaging of the brain and measures of visual function to determine if amiloride is effective as a neuroprotective drug. This will be a randomised control trial, funded by the MS society, for people with their first episode of optic neuritis, with or without a previous diagnosis of MS. Participants will receive either amiloride, or an identical placebo tablet for 5 months, followed 4 times over a total of 12 months. The study is being conducted in the John Radcliffe hospital in Oxford but will also be recruiting patients from Stoke Mandeville hospital, Frimley park hospital, Royal Berkshire Hospital (Reading) and King Edward VII Hospital (Windsor).

Should this trial show a significant benefit from amiloride in ON, it will be an important first step in developing neuroprotective therapies in ON and MS and potentially this could have a significant impact on people with MS and their carers.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13895

Ethics approval

First MREC approval date 21/01/2013, ref: 13/SC/0022

Study design

Randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: Eye, Neurological; Subtopic: Eye (all Subtopics), Neurological (all Subtopics); Disease: Ophthalmology, Nervous system disorders

Intervention

Amiloride, 10mg per day active group with a double blind randomised placebo group.
Study Entry : Single Randomisation only

Intervention type

Drug

Phase

Phase II

Drug names

Amiloride

Primary outcome measures

Scanning Laser Polarimetry determined retinal fibre layer thickness measured at baseline, 6 and 12 months.

Secondary outcome measures

1. Colour Vision measured at baseline, and 6 months
2. Non-conventional surrogate marker of white matter and grey matter injury and connectivity by 3T MRI measured at baseline, 6 and 12 months
3. Optical Coherence Tomography - determined difference in retinal nerve fibre layer thickness measured at baseline, 6 and 12 months
4. Quality of Life Questionnaires measured at baseline, 6 and 12 months
5. Visual Electrophysiology measured at baseline and 6 months
6. Visual Fuction measured at baselne, 6 and 12 months

Overall trial start date

19/03/2013

Overall trial end date

31/03/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with a first episode of unilateral ON
2. Participants with an existing diagnosis of relapsing remitting MS and new onset of ON are eligible if they have not had a previous episode of ON
3. A duration of disease of ≤ 10 years
4. An EDSS (Expanded Disability Status Scale) of ≤3
5. No immune modulating treatment other than β-Interferon or Glatiramer Acetate at time of recruitment
6. Able to be randomised within 28 days of onset of visual symptoms
7. Visual acuity of ≤6/9
8. Participant is willing and able to give informed consent for participation in the study and able to comply with study visits
9. Male or Female, aged between 18 – 55 years.
10. Stable dose of current regular medication for at least 4 weeks prior to study entry
11. Female participants of child bearing potential must be willing to use two effective methods of contraception (barrier methods, hormonal methods or abstinence) during the initial 5 month treatment period of the study and for one month thereafter.
12. Participant has clinically acceptable urea and electrolytes and estimated glomerular filtration rate (eGFR) >60
13. Able and willing to comply with all study requirements.
14. Willing to allow his or her General Practitioner to be notified of participation in the study.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 46; Description: 23 in the active group and 23 in the placebo comparator group

Participant exclusion criteria

1. Previous diagnosis of ON
2. Any concomitant immune suppressing or immune modulating therapy excluding β-interferon or glatiramer acetate.
3. Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
4. Concomitant potassium supplements, angiotensin converting enzyme inhibitors, angiotensin II antagonists, cyclosporine, tacrolimus or lithium
5. Any contra-indication to MRI – severe claustrophobia, metal implant, pacemaker, etc.
6. Participant who is terminally ill or is inappropriate for placebo medication
7. Impaired renal function : eGFR ≤60, anuria, acute or chronic renal insufficiency and evidence of diabetic nephropathy
8. Raised serum potassium (K+ >5.5mmol/l)
9. Diabetes
10. Significant concomitant eye disease in either eye that may affect diseased or fellow eye results.
11. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.
12. Participants who have participated in another research study involving an investigational product in the past 12 weeks.

Recruitment start date

19/03/2013

Recruitment end date

31/03/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Dept of Clinical Neurology
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Charity

Funder name

Multiple Sclerosis Society (of Great Britain & Northern Ireland); Grant Codes: 952/11

Alternative name(s)

MS Society

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

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