Clinical trial NCT02939937
Conditions: Optic Neuritis
Sponsor: Tehran University of Medical Sciences
Start date: 2017-03-09; Completion date: 2019-01-02
Enrollment: 71 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:

Arms: arm 1: patients received phenytoin 100mg three time daily up to 3 months arm 2: patients received placebo 100 mg three time daily for 3 months
Interventions: intervention 1: Phenytoin intervention 2: placebo
Intervention descriptions: intervention 1: 100 mg phenytoin three time daily for three months, and phenytoin levels will be taken at one and three months later. intervention 2: 100 mg placebo three time daily for three months, and phenytoin levels will be taken at one and three months later.

Protocol documents:
SAP_002.pdf: 
Effect of Phenytoin on the Ganglion Cell Layer in Patients with Optic Neuritis 
NCT02939937  
7/5/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis plan: 
The distribution of numerical data is tested for normality using the Shapiro-Wilk 
test. Descriptive statistics are calculated as the mean and standard deviation. 
Categorical variables are compared using the chi-square test. To evaluate the 
changes of thicknesses of different layers over 6 months, a repeated-measures, 
mixed-effects model is used. The dependent variables were the layer thicknesses, 
visual field, and visual acuity measured at 3 time points: baseline, one month, and 
6 months. We report the amount of ganglion cell inner plexiform layer thickness 
changes at baseline, one month and six months between placebo and phenytoin 
group using linear mixed model. Multiple linear regression will be used to test a set 
of OCT variables (models) obtained at the onset of the study and after 1 month, to 
predict the visual acuity outcomes by month 6.  
 
 
 

ICF_001.pdf: 
Effect of Phenytoin on the Ganglion Cell Layer in Patients with Optic Neuritis 
NCT02939937 
April 15, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
[Informed Consent form] 
 
This Informed Consent Form is for men and women who attend FARABI EYE HOSPITAL, and who we are 
inviting to participate in research on optic neuritis. The title of our research project is "Effect of 
phenytoin on the ganglion cell inner layer thickness and visual field in patients with acute optic neuritis." 
Optic neuritis is an inflammation that damages the optic nerve, a bundle of nerve fibers that transmits 
visual information from your eye to your brain. Pain and temporary vision loss in one eye are common 
symptoms of optic neuritis. The drugs that are currently used to help people with optic neuritis do not 
prohibit nerve fiber loss which is the main cause for loss of vision in optic neuritis. Also, the high-dose 
regimen used is associated with some recognized adverse effects. There is a drug which is suggested to 
better save the nerve fibers. The reason we are doing this research is to find out if this is actually true. 
This research will involve taking oral medicines thrice daily as well as two follow-up visits to the clinic. 
We are inviting all adults with unilateral acute optic neuritis who attend FARABI EYE HOSPITAL to 
participate in the research on this drug. Your participation in this research is entirely voluntary. It is your 
choice whether to participate or not. Whether you choose to participate or not, all the services you 
receive at this clinic will continue and nothing will change. If you choose not to participate in this 
research project, you will be offered the treatment that is routinely offered in this clinic/hospital for 
disease optic neuritis, and we will tell you more about it later. You may change your mind later and stop 
participating even if you agreed earlier. The drug we are testing in this research is called phenytoin. You 
should know the possible side effects associated with this drug: • fever, swollen glands, sore throat, 
trouble breathing, painful mouth sores, sores around your eyes; • skin rash, easy bruising or bleeding, 
severe weakness; • severe muscle pain; • nausea, vomiting, upper stomach pain, loss of appetite, dark 
urine, jaundice (yellowing of the skin or eyes); • bone pain (especially in your hips, legs, or lower back), 
trouble with walking; or • severe skin reaction--fever, sore throat, swelling in your face or tongue, 
burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face 
or upper body) and causes blistering and peeling. Common phenytoin side effects may include: • 
dizziness, drowsiness, confusion, nervousness; • nausea, vomiting, constipation; • tremors, slurred 
speech, loss of balance or coordination; • rash; • abnormal eye movement; • headache; or • sleep 
problems (insomnia). A placebo or inactive medicine looks like real medicine but it is not. It is a dummy 
or pretend medicine. It has no effect on a person because it has no real medicine in it. Sometimes when 
we want to know whether a new medicine is good, we give some people the new medicine and some 
people the pretend or dummy medicine. For the research to be good, it is important that you do not 
know whether you have been given the real medicine or the pretend or dummy medicine. This is one of 
the best ways we have for knowing what the medicine we are testing really does. The research takes 
place over six months. In total, you will be asked to come 2 times to the clinic. At the end of six months, 
the research will be finished. We will follow you closely and keep track of any unwanted effects or any 
problems. We may refer you to some other medical specialists to manage the symptoms of the side 
effects or reactions. Or, we may stop the use of the drug. If this is necessary, we will discuss it together 
with you and you will always be consulted before we move to the next step. By participating in this 
research it is possible that you will be at greater risk than you would otherwise be. There is, for example, 
a risk that your disease will not get better. The information that we collect from this research project 


will be kept confidential. Information about you that will be collected during the research will be put 
away and no-one but the researchers will be able to see it. Any information about you will have a 
number on it instead of your name. Only the researchers will know what your number is and we will lock 
that information up with a lock and key. It will not be shared with or given to anyone except doctor 
Gholizadeh, Dr. Aghsaiifard, Dr. Yadegari, and the University Ethics Board, in order to monitor 
preservation of my rights. You do not have to take part in this research if you do not wish to do so. You 
may also stop participating in the research at any time you choose. It is your choice and all of your rights 
will still be respected. If you do not wish to take part in the research, you will be provided with the 
established standard treatment available at the clinic. If you have any questions you may ask them now 
or later, even after the study has started. If you wish to ask questions later, you may contact any of the 
following: Dr. Alireza Gholizadeh, FARABI EYE HOSPITAL, Tehran, Iran I have read the foregoing 
information, or it has been read to me. I have had the opportunity to ask questions about it and any 
questions that I have asked have been answered to my satisfaction. I consent voluntarily to participate 
as a participant in this research. Print Name of Participant__________________ Signature of Participant 
___________________ Date ___________________________ Day/month/year 

Prot_000.pdf: 
Effect of Phenytoin on the Ganglion Cell Layer in Patients 
with Optic Neuritis 
 
NCT02939937 
4/14/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study Protocol  
Optic neuritis is diagnosed based on the sudden loss of unilateral vision in a person aged 18- 60 with 
painful eye movements and colored vision impairment, as well as pupil defects and associated visual 
impairment (confirmed by neuro-ophthalmologist). Patients entered It should be kept alert to another 
eye plan. There is also no primary pathology in Oct. The control group was selected as cohort and dual 
blind randomized. 108 patients referred to Farabi Hospital during the years 2016 to 2018 were 
diagnosed with optic neuritis in a one-to-one treatment with 300 mg daily for Phenytoin and placebo at 
the first 14 days after Detect Optic Neuritis. All patients are treated for corticosteroids for an acute 
phase with a 1 g daily intravenous methylprednisolone daily for 3-5 days. EXCLUSION CRITERIA Previous 
history of optic neuritis in the contralateral eye-recurrence in the same eye-Eye disease that affects the 
study at the same time - Clinical hepatitis or proven laboratory testsDisorders of the kidney or heart 
function (such as disturbed electrocardiogram) - Contraindication of Phenytoin intake (such as 
pregnancy) Or previous sensitivity to Phenytoin ) - Using sodium or calcium channel blockers over two 
weeks before starting Phenytoin and receiving other immunosuppressive drugs during the 2 months 
prior to treatment - IOP greater than 21 - Refractive error greater than 5 diopters The initial examination 
consists of the best corrected visual acuity , applanation tonometry, slit examination and funduscopy. 
Best corrected visual acuity is converted to logMAR (logarithms of minimum angle of resolution) by 
statistical calculation. In all patients, the visual field is performed by the Swedish interactive 
thresholding algorithm standard 24-2 perimeter (Carl Zeiss mediated, Dublin, California). The false 
positives are less than 13%, the false negative are less than 30% acceptable. The light sensitivity in the 
visual field is measured by the decibel (db). All patients have Optical Coherence Tomography. The 
thickness of RNFL and MACULA and GCIPL are evaluated in 8 sectors:these stages in the first and sixth 
month after the onset of the disease It repeats itself. Then, the relationship of values obtained in 
macular thicknesses and GCIPLs with VF is compared at different times. Data are analyzed by SPSS 
version 20 software.