Amiloride Clinical Trial In Optic Neuritis
Condition: Optic Neuritis; Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Neuritis; Optic Neuritis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): Amiloride; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Placebo capsule identical in appearance to Amiloride 10mg capsule
Other intervention name(s): Midamor
Intervention MeSH terms: Amiloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Optic neuritis; Multiple sclerosis; Retinal nerve fibre layer; Axonal loss; Neuroprotection; MRI; Optical coherence tomography; Amiloride; Acid Sensing Ion Channels