Optic Neuritis
Conditions
Brief summary
Optic neuritis typically occurs in young (mean age, 32 years), female (77%) patients, and it presents as subacute monocular visual loss that develops over several days. As yet, treatment with intravenous corticosteroid for optic neuritis had no long-term beneficial effect on vision. There are a number of factors that contribute to nerve fibre damage including increased level of sodium, so blocking sodium entry could help to protect them against damage. The main objective of the study is determine whether phenytoin (which blocks sodium entry) can protect nerve fibre and improve final visual function after optic neuritis.
Interventions
DRUGPhenytoin
100 mg phenytoin three time daily for three months, and phenytoin levels will be taken at one and three months later.
DRUGplacebo
100 mg placebo three time daily for three months, and phenytoin levels will be taken at one and three months later.
Sponsors
Tehran University of Medical Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
participant , investigator
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* isolated, unilateral, first acute optic neuritis (confirmed by neuroophthalmologist) * willing to receive a steroidal regimen * no pathologic finding in first oct * no pathology and history of optic neuritis in contralateral eye * \<14 days since onset visual loss
Exclusion criteria
* Contraindication or known allergy to Phenytoin * Use of a calcium channel or sodium channel blocker in the past 2 months * Corticosteroid use in the past 2 months * Pregnancy * Significant cardiac, renal or liver abnormalities * Prior clinical episode of optic neuritis in either eye * Bilateral acute optic neuritis * Known ocular or neurological conditions or abnormalities other than refractive error that impair visual function * Refractive error of greater than +5 or -5 diopters * Any condition that may interfere with performance of Optical Coherence Tomography (OCT): corneal, lens or fundoscopic abnormality, a co-morbid ocular condition not related to optic neuritis as detected on the OCT reading
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retinal Ganglion Cell Inner Plexiform Layer Thickness | Measured at baseline and month 1, 6 | ganglion cell inner plexiform layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography |
| Macular Layer Thickness | Measured at baseline and month 1, 6 | macular layer thickness measure in 8 sectors by Heidelberg spectral domain Optical Coherence Tomography |
| Best Corrected Visual Acuity | at baseline and month 6 | Best corrected visual acuity is converted to logMAR (logarithms of minimum angle of resolution) by statistical calculation. |
| Visual Field Mean Deviation in Decibel | Measured at baseline and month 6 | The visual field is performed by the Swedish interactive thresholding algorithm standard 24-2 perimeter (Carl Zeiss mediated, Dublin, California). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retinal Nerve Fibre Layer Thickness in Micrometer | Measured at baseline and month1 ,6 | Retinal nerve fibre layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography |
Countries
Iran
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phenytoin patients received phenytoin 100mg three time daily up to 3 months
Phenytoin: 100 mg phenytoin three time daily for three months, and phenytoin levels will be taken at one and three months later. | 21 |
| Placebo patients received placebo 100 mg three time daily for 3 months
placebo: 100 mg placebo three time daily for three months, and phenytoin levels will be taken at one and three months later. | 50 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Phenytoin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 71 Participants | 21 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Iran | 47 participants | 62 participants | 15 participants |
| Sex: Female, Male Female | 40 Participants | 54 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 50 |
| other Total, other adverse events | 4 / 21 | 0 / 50 |
| serious Total, serious adverse events | 1 / 21 | 0 / 50 |
Outcome results
Primary
Best Corrected Visual Acuity
Best corrected visual acuity is converted to logMAR (logarithms of minimum angle of resolution) by statistical calculation.
Time frame: at baseline and month 6
Population: incomplete follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenytoin | Best Corrected Visual Acuity | baseline | 1.44 log mar | Standard Deviation 0.98 |
| Phenytoin | Best Corrected Visual Acuity | 6 months | 0.04 log mar | Standard Deviation 0.067 |
| Placebo | Best Corrected Visual Acuity | baseline | 1 log mar | Standard Deviation 0.83 |
| Placebo | Best Corrected Visual Acuity | 6 months | 0.13 log mar | Standard Deviation 0.448 |
Primary
Macular Layer Thickness
macular layer thickness measure in 8 sectors by Heidelberg spectral domain Optical Coherence Tomography
Time frame: Measured at baseline and month 1, 6
Population: incomplete follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenytoin | Macular Layer Thickness | 6 months | 269 micron | Standard Deviation 28.29 |
| Phenytoin | Macular Layer Thickness | baseline | 262.73 micron | Standard Deviation 22.02 |
| Phenytoin | Macular Layer Thickness | 1 month | 255 micron | Standard Deviation 19.72 |
| Placebo | Macular Layer Thickness | 1 month | 264.39 micron | Standard Deviation 22.53 |
| Placebo | Macular Layer Thickness | baseline | 265.98 micron | Standard Deviation 22.5 |
| Placebo | Macular Layer Thickness | 6 months | 268.37 micron | Standard Deviation 22.69 |
Primary
Retinal Ganglion Cell Inner Plexiform Layer Thickness
ganglion cell inner plexiform layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography
Time frame: Measured at baseline and month 1, 6
Population: incomplete follow up from baseline to 6 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenytoin | Retinal Ganglion Cell Inner Plexiform Layer Thickness | baseline | 36.56 micron | Standard Deviation 6.61 |
| Phenytoin | Retinal Ganglion Cell Inner Plexiform Layer Thickness | 1 month | 31 micron | Standard Deviation 6.61 |
| Phenytoin | Retinal Ganglion Cell Inner Plexiform Layer Thickness | 6 months | 30.70 micron | Standard Deviation 5.56 |
| Placebo | Retinal Ganglion Cell Inner Plexiform Layer Thickness | baseline | 34.65 micron | Standard Deviation 8.49 |
| Placebo | Retinal Ganglion Cell Inner Plexiform Layer Thickness | 1 month | 29.42 micron | Standard Deviation 5.98 |
| Placebo | Retinal Ganglion Cell Inner Plexiform Layer Thickness | 6 months | 32.12 micron | Standard Deviation 9.1 |
Primary
Visual Field Mean Deviation in Decibel
The visual field is performed by the Swedish interactive thresholding algorithm standard 24-2 perimeter (Carl Zeiss mediated, Dublin, California).
Time frame: Measured at baseline and month 6
Population: incomplete follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenytoin | Visual Field Mean Deviation in Decibel | Baseline visual field mean deviation (MD) | -17.07 db | Standard Deviation 11.41 |
| Phenytoin | Visual Field Mean Deviation in Decibel | 6 months MD | -3.89 db | Standard Deviation 4.46 |
| Placebo | Visual Field Mean Deviation in Decibel | Baseline visual field mean deviation (MD) | -17.76 db | Standard Deviation 11.81 |
| Placebo | Visual Field Mean Deviation in Decibel | 6 months MD | -5.16 db | Standard Deviation 7.49 |
Secondary
Retinal Nerve Fibre Layer Thickness in Micrometer
Retinal nerve fibre layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography
Time frame: Measured at baseline and month1 ,6
Population: incomplete follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenytoin | Retinal Nerve Fibre Layer Thickness in Micrometer | Baseline | 131.8 micron | Standard Deviation 36.56 |
| Phenytoin | Retinal Nerve Fibre Layer Thickness in Micrometer | 1 month | 93.85 micron | Standard Deviation 8.64 |
| Phenytoin | Retinal Nerve Fibre Layer Thickness in Micrometer | 6 months | 77.7 micron | Standard Deviation 20.03 |
| Placebo | Retinal Nerve Fibre Layer Thickness in Micrometer | Baseline | 124.87 micron | Standard Deviation 47.51 |
| Placebo | Retinal Nerve Fibre Layer Thickness in Micrometer | 1 month | 97.41 micron | Standard Deviation 23 |
| Placebo | Retinal Nerve Fibre Layer Thickness in Micrometer | 6 months | 78.61 micron | Standard Deviation 18.97 |