Neuroprotection With Phenytoin in Optic Neuritis
A Phase II Double Blind, Randomized, Placebo Controlled Trial of Neuroprotection With Phenytoin in Acute Optic Neuritis
What it found
The main measure showed a statistically significant benefit.
“Mean 6-month RNFL thickness in the affected eye at 6 months was 81.46 μm (SD 16.27) in the phenytoin group (a mean decrease of 16.69 μm [SD 13.73] from baseline) versus 74.29 μm (15.14) in the placebo group (a mean decrease of 23.79 μm [13.97] since baseline; adjusted 6-month difference of 7.15 μm [95% CI 1.08-13.22]; p=0.021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo.”Read by software from the paper's abstract
retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline · 6 months
| Group | n | Value |
|---|---|---|
| phenytoin | 39 | 81.46 μm (SD 16.27) |
| placebo | 42 | 74.29 μm (15.14) |
adjusted 6-month mean difference 7.15 μm
p = 0.021
Total participants: 86
Read by software from the paper's abstract
What was tested
Treatment tested
- Phenytoin
Sodium channel alpha subunit blocker
Placebo
- Placebo
What it measured
Main measures
Mean Retinal nerve fibre layer thickness
Measured at entry and after 6 months
Retina scans (OCT)
Other measures (3)
Visual function
Measured at entry and 6 months
VisionVisual evoked potentials
Measured at entry (or within 4 weeks) and after 6 months
Myelin repairOptic nerve and brain MRI
Brain MRI will be performed at entry(or within 4 weeks) Optic nerve MRI will be performed at entry (or within 4 weeks) and after 6 months
MRI lesionsMyelin repair
Who could take part
MS (type not specified) · 18 to 60
Show the full criteria
Inclusion criteria
* Diagnosis of acute optic neuritis * Visual acuity in affected eye ≤ 6/12 * Corrected vision in normal eye ≥ 6/6 * No history of optic neuritis or other ocular disease in either eye * ≤ 14 days since onset of visual loss
Exclusion criteria
* Contraindication or known allergy to Phenytoin * Contraindication to MRI * Use of a calcium channel or sodium channel blocker in the past 2 months * Corticosteroid use in the past 2 months * Tysabri infusion in the past 3 months * MS with major temperature dependent disability * Relapsing remitting MS of greater than 10 yrs duration or EDSS>3 * Pregnancy * Breast Feeding * Significant cardiac, renal or liver abnormalities
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
Optic neuritis is caused by inflammation of the optic nerve and causes loss of vision in the affected eye. It is often associated with multiple sclerosis. Loss of vision after an attack of optic neuritis is caused by damage to the nerve fibres in the optic nerve. There are a number of factors that contribute to nerve fibre damage including increased levels of sodium within them, so blocking sodium entry could help to protect them against damage. The purpose of this study is determine whether phenytoin (which blocks sodium entry into cells) can protect against loss of nerve fibres and prevent loss of vision after optic neuritis.
Papers
Results
Effects of Phenytoin on the Retinal Ganglion Cell-Inner Plexiform Layer in Acute Optic Neuritis: Analysis of a Phase II Randomized Trial.Neurology · 2025
Results
Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.BMJ Open · 2016
Results
Raftopoulos R, Hickman SJ, Toosy A, Sharrack B, Mallik S, Paling D, Altmann DR, Yiannakas MC, Malladi P, Sheridan R, Sarrigiannis PG, Hoggard N, Koltzenburg M, Gandini Wheeler-Kingshott CA, Schmierer K, Giovannoni G, Miller DH, Kapoor R. Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Mar;15(3):259-69. doi: 1Mean 6-month RNFL thickness in the affected eye at 6 months was 81.46 μm (SD 16.27) in the phenytoin group (a mean decrease of 16.69 μm [SD 13.73] from baseline) versus 74.29 μm (15.14) in the placebo group (a mean decrease of 23.79 μm [13.97] since baseline; adjusted 6-month difference of 7.15 μm [95% CI 1.08-13.22]; p=0.021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo.
Read by software from the paper's abstract
Results
Counihan TJ, Duignan JA, Gormley G, Saidha S, Dooley C, Newell J. Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study. Ir J Med Sci. 2014 Mar;183(1):117-21. doi: 10.1007/s11845-013-1042-7. Epub 2013 Nov 28.
Loading reviews and guidelines…
Related trials
- Cannabis (THC vs. CBD) in Multiple Sclerosis
Phase 2 · Recruiting
Still running
- ANTIBIOBONTA - Assessment of the interest of a peri-operative antibiot
Phase 3 · Not yet recruiting
Still running
- A study to asses the effects of Nabiximols on spasticity associated wi
Phase 3 · Completed
No results found
- Evaluation of the Effect of Nabiximols Oromucosal Spray on Clinical Me
Phase 3 · Stopped early
Stopped
- Trial to Evaluate the Effect of Nabiximols Oromucosal Spray on Clinica
Phase 3 · Completed
Missed its main goal
- Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Ther
Phase 3 · Stopped early
Stopped
History
Started
Nov 2011
Main results due
Dec 2014
Finished
Mar 2015