Excitement then Ugh-Amilioride in BMJ

McKee JB, Elston J, Evangelou N, Gerry S, Fugger L, Kennard C, Kong Y, Palace J, Craner M.Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial. BMJ Open. 2015;5(11):e009200.

INTRODUCTION:Neurodegeneration is a widely accepted contributor to the development of long-term disability in multiple sclerosis (MS). While current therapies in MS predominantly target inflammation and reduce relapse rate they have been less effective at preventing long-term disability. The identification and evaluation of effective neuroprotective therapies within a trial paradigm are key unmet needs. Emerging evidence supports amiloride, a licenced diuretic, as a neuroprotective agent in MS through acid sensing ion channel blockade. Optic neuritis (ON) is a common manifestation of MS with correlates of inflammation and neurodegeneration measurable within the visual pathways. Amiloride Clinical Trial In Optic Neuritis (ACTION) will utilise a multimodal approach to assess the neuroprotective efficacy of amiloride in acute ON.
METHODS AND ANALYSIS: 46 patients will be recruited within 28 days from onset of ON visual symptoms and randomised on a 1:1 basis to placebo or amiloride 10 mg daily. Double-blinded treatment groups will be balanced for age, sex and visual loss severity by a random-deterministic minimisation algorithm. The primary objective is to demonstrate that amiloride is neuroprotective in ON as assessed by scanning laser polarimetry of the peripapillary retinal nerve fibre layer (RNFL) thickness at 6 months in the affected eye compared to the unaffected eye at baseline. RNFL in combination with further retinal measures will also be assessed by optical coherence tomography. Secondary outcome measures on brain MRI will include cortical volume, diffusion-weighted imaging, resting state functional MRI, MR spectroscopy and magnetisation transfer ratio. In addition, high and low contrast visual acuity, visual fields, colour vision and electrophysiology will be assessed alongside quality of life measures.
ETHICS AND DISSEMINATION:Ethical approval was given by the south central Oxford B research ethics committee (REC reference: 13/SC/0022). The findings from ACTION will be disseminated through peer-reviewed publications and at scientific conferences.
TRIAL REGISTRATION NUMBER: EudraCT2012-004980-39, ClinicalTrials.gov Identifier: NCT01802489.


I got really excited by the title and thought has it worked? But why is it in BMJ open and not Lancet and then I rea and ugh it is another protocol paper. The trial was suppossed to be finished by now according to clinical trials.gov. 

Strengths and limitations of this study
This study examines optic neuritis as a discrete central nervous system inflammatory event with measurable structural and clinical outcomes allowing the time-efficient (6 month) assessment of neuroprotective therapies.

The repurposing of amiloride, a licenced diuretic with excellent safety record, as a neuroprotective therapy is supported by a strong basic and clinical science with potential to translate to multiple sclerosis (MS).

A multimodal approach including retinal scans and brain MRI will examine the effect of the intervention from the retina to the brain allowing the evaluation of sensitive outcome markers and inform structural–functional correlates for future studies of optic neuritis.

Neuronal loss can occur early in acute inflammation, therefore recruitment up to 28 days may be outside the effective ‘therapeutic window’ for neuroprotection.

The primary outcome measure uses the unaffected eye as a powerful comparator, but this eye may be affected by MS-related changes or previous subclinical optic neuritis, thus confounding the results.


This compound has been in a PPMS study and this phase II and it is in MS SMART... a phase II again, so will we need a phase III. The patent filed may then be all but useless so may have to hope that it will be prescribed off-label if it works. That will be great until pharma get an alternative...anyway we wait for that day

I remain hopeful for the results which I want to read...if you want a protocol here you go....however you could have gone to clinical trials.gov:-).


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