Contributions
Abstract: 102
Type: Oral
Abstract Category: Therapy - disease modifying - Neuroprotection
Basic science and early clinical trial evidence suggest amiloride may exert a neuroprotective effect in Multiple Sclerosis (MS) through blockade of the acid sensing ion channel (ASIC). Optic neuritis (ON) is a discrete CNS inflammatory event leading to neuro-axonal injury. The extent of neuro-axonal injury can be assessed by the thickness of the retinal nerve fibre layer (RNFL) by scanning laser polarimetry (GDx) and optical coherence tomography (OCT). Thus, we examined the neuroprotective efficacy of amiloride in acute ON in a phase II, double blind, randomised controlled trial utilising GDx and OCT (NCT01802489).
Participants aged 18-55 years were recruited within 28 days of onset with a first episode of unilateral ON including patients with MS, providing diagnosis was within 10 years and EDSS < 3.0. They were randomised to amiloride 10mg/day or placebo for 5 months. Exclusion criteria included diabetes, raised potassium, or disease modifying therapy except β-interferon or glatiramer acetate. All study procedures were conducted at the John Radcliffe Hospital Oxford, UK.
Primary outcome measure was the difference between amiloride and placebo groups in the GDx derived affected eye RNFL thickness at 6 months compared to baseline in the unaffected eye. Secondary outcome measures included; OCT derived RNFL thickness at 6 months, and by both modalities at 12 months, visually evoked potentials (VEP), pattern electro-retinogram, high and low contrast visual acuity, Humphrey visual field and Farnsworth Munswell 100 hue colour vision scores.
48 patients were recruited. 3 withdrew due to alternative diagnosis, 1 withdrew consent and 1 was lost to follow up, leaving an ITT cohort of 43 patients; 23 placebo, and 20 amiloride. There were no significant drug related adverse events.
No significant differences were found between groups in the primary outcome measure (p=0.84) and no significant difference in visual measures at 6 or 12 months. VEPs were significantly prolonged in the amiloride group compared to placebo (p=0.004).
In summary, our trial failed to show any neuroprotective benefit of amiloride in clinical and surrogate measures within acute ON.
Disclosure:
Justin Mckee - nothing to disclose
Nikos Evangelou - nothing to disclose
Stephen Gerry - nothing to disclose
Lars Fugger - nothing to disclose
Christopher Kennard - nothing to disclose
Yazuo Kong - nothing to disclose
Charles Cottriall - nothing to disclose
Jackie Palace - nothing to disclose
Abigail Koelewyn - nothing to disclose
Matthew Craner - nothing to disclose
John Elston - nothing to disclose
Abstract: 102
Type: Oral
Abstract Category: Therapy - disease modifying - Neuroprotection
Basic science and early clinical trial evidence suggest amiloride may exert a neuroprotective effect in Multiple Sclerosis (MS) through blockade of the acid sensing ion channel (ASIC). Optic neuritis (ON) is a discrete CNS inflammatory event leading to neuro-axonal injury. The extent of neuro-axonal injury can be assessed by the thickness of the retinal nerve fibre layer (RNFL) by scanning laser polarimetry (GDx) and optical coherence tomography (OCT). Thus, we examined the neuroprotective efficacy of amiloride in acute ON in a phase II, double blind, randomised controlled trial utilising GDx and OCT (NCT01802489).
Participants aged 18-55 years were recruited within 28 days of onset with a first episode of unilateral ON including patients with MS, providing diagnosis was within 10 years and EDSS < 3.0. They were randomised to amiloride 10mg/day or placebo for 5 months. Exclusion criteria included diabetes, raised potassium, or disease modifying therapy except β-interferon or glatiramer acetate. All study procedures were conducted at the John Radcliffe Hospital Oxford, UK.
Primary outcome measure was the difference between amiloride and placebo groups in the GDx derived affected eye RNFL thickness at 6 months compared to baseline in the unaffected eye. Secondary outcome measures included; OCT derived RNFL thickness at 6 months, and by both modalities at 12 months, visually evoked potentials (VEP), pattern electro-retinogram, high and low contrast visual acuity, Humphrey visual field and Farnsworth Munswell 100 hue colour vision scores.
48 patients were recruited. 3 withdrew due to alternative diagnosis, 1 withdrew consent and 1 was lost to follow up, leaving an ITT cohort of 43 patients; 23 placebo, and 20 amiloride. There were no significant drug related adverse events.
No significant differences were found between groups in the primary outcome measure (p=0.84) and no significant difference in visual measures at 6 or 12 months. VEPs were significantly prolonged in the amiloride group compared to placebo (p=0.004).
In summary, our trial failed to show any neuroprotective benefit of amiloride in clinical and surrogate measures within acute ON.
Disclosure:
Justin Mckee - nothing to disclose
Nikos Evangelou - nothing to disclose
Stephen Gerry - nothing to disclose
Lars Fugger - nothing to disclose
Christopher Kennard - nothing to disclose
Yazuo Kong - nothing to disclose
Charles Cottriall - nothing to disclose
Jackie Palace - nothing to disclose
Abigail Koelewyn - nothing to disclose
Matthew Craner - nothing to disclose
John Elston - nothing to disclose