Optic; Neuritis, With Demyelination Clinical Trial
Official title:
A Randomized, Placebo-Controlled, Double-Blind, Phase IIa Study of Amiloride in the Treatment of Acute Autoimmune Optic Neuritis
Following acute inflammation of the optic nerve region, as commonly seen in multiple sclerosis patients, the optic nerve often undergoes atrophy, thus representing permanent damage. Data from animal studies suggest that amiloride may prevent this process. The aim of this study is to assess a potential neuroprotective effect of amiloride in acute autoimmune inflammation of the optic nerve region.
Recent studies have shown that the acid-sensing ion channel 1 (ASIC1) contributes to the
axonal degeneration in CNS lesions Physiologically, ASIC1 has been described as a
postsynaptic proton receptor on hippocampal neurons influencing the intracellular Ca2+
concentration. In MS, ASIC1 seems to activate under acidic conditions predominating in the
inflammatory CNS lesions leading to a Na+ and Ca2+ overload and consecutive damage and
apoptosis of axons. Consecutively, in a MS mousemodel axonal damage was significantly less
pronounced after administering amiloride, a clinically safe blocker of ASICs. So ASIC1 seems
to play a major role in axonal degeneration in MS. To our knowledge no clinical studies have
tested those promising in vitro results in humans so far.
Only one retrospective registry-based cohort study was performed. This study showed no
difference in the risk of incident MS or hospitalization and death among MS patients using
amilorid compared to those using thiazide diuretics. However, this study has numerous
limitations with respect to it's retrospective designone and the fact that amilorid users
were at the vast majority older individuals. Such a late stage of the MS course does not
seem to be the best window of opportunity for interventions with neuroprotective agents.
Moreover, death may be a too multifactorial parameter to correspond with axonal damage
alone. Consequently, a more sensitive parameter for axonal damage in MS is needed to test
the impact of amiloride on neuroprotection and repair.Based on the findings described above
we intend to assess the potential neuroprotective effect of amiloride hydrochlorothiazide
(Amilostad HCT®) in patients with optic neuritis (ON), which has already been demonstrated
in a mouse model. ON is one of the most common manifestations of MS and has already been
proven appropiate to test neuroprotective agents.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
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