Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial

Justin B. McKee, Charles L. Cottriall, John Elston, Simon Epps, Nikos Evangelou, Stephen Gerry, Christopher Kennard, Yazhuo Kong, Abigail Koelewyn, Wilhelm Kueker, Maria Isabel Leite, Jacqueline Palace, Matthew Craner*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)

Abstract

Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18–55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo (clinicaltrials.gov, NCT 01802489). Results: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx (p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo (p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.

Original languageEnglish
Pages (from-to)246-255
Number of pages10
JournalMultiple Sclerosis Journal
Volume25
Issue number2
Early online date27 Nov 2017
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • axonal loss
  • Clinical trial
  • multiple sclerosis
  • outcome measurement

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    McKee, J. B., Cottriall, C. L., Elston, J., Epps, S., Evangelou, N., Gerry, S., Kennard, C., Kong, Y., Koelewyn, A., Kueker, W., Leite, M. I., Palace, J., & Craner, M. (2019). Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial. Multiple Sclerosis Journal, 25(2), 246-255. https://doi.org/10.1177/1352458517742979