Dr Matthew Craner
Dept of Clinical Neurology
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
First MREC approval date 21/01/2013, ref: 13/SC/0022
Randomised interventional treatment trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Topic: Eye, Neurological; Subtopic: Eye (all Subtopics), Neurological (all Subtopics); Disease: Ophthalmology, Nervous system disorders
Amiloride, 10mg per day active group with a double blind randomised placebo group.
Study Entry : Single Randomisation only
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
Overall trial end date
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.
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)
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 participants 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
Recruitment end date
Countries of recruitment
Trial participating centre
Dept of Clinical Neurology
University of Oxford (UK)
Multiple Sclerosis Society (of Great Britain & Northern Ireland); Grant Codes: 952/11
Funding Body Type
private sector organisation
Funding Body Subtype
professional associations and societies
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