Optic neuritis (ON) is a common event in Multiple Sclerosis (MS), and causes significant loss of nerve cells in the eye, resulting in poor vision. Optic neuritis 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.

The investigators have identified through laboratory and early clinical research in humans that amiloride (a water tablet already in use) may be a drug that can be of benefit in optic neuritis by protecting from loss of nerves cells, ie a neuroprotective drug.

The purpose of this study is to assess the efficacy of amiloride as a neuroprotective drug in optic neuritis

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. In addition to the inflammatory episodes in MS, axonal and neuronal damage occurs. It is this axonal loss which is thought to be the major pathological substrate for disability in MS.

Acute inflammatory demyelinating optic neuritis is a common event in multiple sclerosis. Following optic neuritis there is axonal loss in the optic nerve and retina, which if severe can result in a poor visual recovery. Uniquely amongst central nervous system (CNS) structures, the structural and functional changes in the eye during and following optic neuritis provide a sensitive way of observing neurodegeneration and testing the effectiveness of potential neuroprotective agents. In optic neuritis it has been shown that thinning of the retinal nerve fibre layer takes place, and by 6 months this thinning is established and has largely stabilised. This represents axonal loss in the anterior visual system. The degree of this thinning has been shown to correlate with the amount of vision recovered following optic neuritis, the more thinning that occurs, the poorer the outcome. The thickness of the retinal nerve fibre layer can be measured by the simple scanning techniques of scanning laser polarimetry (GDx) and optical coherence tomography (OCT).

Axonal loss in MS is likely to be multifactorial, but a key end point is the influx of sodium and calcium ions. Recent research suggests that in the inflammatory environment of optic neuritis, the acid sensing ion channel may have an important role in this influx of sodium and calcium, and therefore in axonal loss in MS. The drug amiloride, already in use as a diuretic, is a known blocker of this ion channel. The investigators have identified through laboratory and early clinical research in humans that by blockade of the acid sensing ion channel, amiloride may be neuroprotective in optic neuritis and MS.

The investigators primary objective is to assess the neuroprotective efficacy of amiloride in optic neuritis through the surrogate measure of retinal nerve fibre layer measurement. Secondary objectives are to assess markers of neurodegeneration in ON and the neuroprotective effect of amiloride through non-conventional MRI outcomes, to assess if amiloride improves functional and visual outcome following optic neuritis, and to confirm optic neuritis as a sensitive and efficient model for neuroprotection in a clinical trial framework.

46 Participants will be recruited to receive either amiloride, or an identical placebo capsule for 5 months. The primary outcome will be measured at 6 months, with a further measure at 12 months.

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

Inclusion Criteria:

• Participants with a first episode of unilateral optic neuritis

• Participants with an existing diagnosis of relapsing remitting MS and new onset of ON are eligible if they have;

  1. Not had a previous episode of optic neuritis,
  2. A duration of disease of ≤10 years
  3. An EDSS (Expanded Disability Status Scale) of ≤3.
  4. No immune modulating treatment other than β-Interferon or glatiramer acetate at time of recruitment

• Able to be randomised within 28 days of onset of visual symptoms

• Visual acuity of ≤6/9

• Participant is willing and able to give informed consent for participation in the study and able to comply with study visits

• Male or Female, aged between18 - 55 years.

• Stable dose of current regular medication for at least 4 weeks prior to study entry.

• Participant has clinically acceptable urea and electrolytes and estimated glomerular filtration rate (eGFR) >60

• Able and willing to comply with all study requirements.

• Willing to allow his or her General Practitioner to be notified of participation in the study.

Exclusion Criteria:

• Previous diagnosis of optic neuritis
• Any concomitant immune suppressing or immune modulating therapy excluding β-interferon or glatiramer acetate.
• Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
• Concomitant potassium supplements, angiotensin converting enzyme inhibitors, angiotensin II antagonists, cyclosporine, tacrolimus or lithium
• Any contra-indication to MRI - severe claustrophobia, metal implant, pacemaker, etc.
• Participant who is terminally ill or is inappropriate for placebo medication
• Impaired renal function : eGFR ≤60, anuria, acute or chronic renal insufficiency and evidence of diabetic nephropathy
• Raised serum potassium (K+ >5.5mmol/l)
• Diabetes
• Significant concomitant eye disease in either eye that may affect diseased or fellow eye results.
• 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.
• Participants who have participated in another research study involving an investigational product in the past 12 weeks.