Effect of Phenytoin on the Ganglion Cell Layer in Patients With Optic Neuritis

a Phase II Double Blind, Randomized, Placebo Controlled Trial of Effect of Phenytoin on the Ganglion Cell Inner Plexiform Layer (GCIPL) Thickness and Visual Field in Patients With a First Episode of Acute Optic Neuritis

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.

Study Overview

• Status: Completed
• Conditions: Optic Neuritis
• Intervention / Treatment: Drug: Phenytoin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 3542168325
    • Eye Research Center Farabi Hosoital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phenytoin; patients received phenytoin 100mg three time daily up to 3 months	Drug: Phenytoin; 100 mg phenytoin three time daily for three months, and phenytoin levels will be taken at one and three months later.; Other Names: epanutin
Experimental: placebo; patients received placebo 100 mg three time daily for 3 months	Drug: placebo; 100 mg placebo three time daily for three months, and phenytoin levels will be taken at one and three months later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal Ganglion Cell Inner Plexiform Layer Thickness	ganglion cell inner plexiform layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography	Measured at baseline and month 1, 6
Macular Layer Thickness	macular layer thickness measure in 8 sectors by Heidelberg spectral domain Optical Coherence Tomography	Measured at baseline and month 1, 6
Best Corrected Visual Acuity	Best corrected visual acuity is converted to logMAR (logarithms of minimum angle of resolution) by statistical calculation.	at baseline and month 6
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).	Measured at baseline and month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal Nerve Fibre Layer Thickness in Micrometer	Retinal nerve fibre layer thickness measure in 8 sectors by Heidelberg spectral-domain Optical Coherence Tomography	Measured at baseline and month1 ,6

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Actual): November 11, 2018
• Study Completion (Actual): January 2, 2019

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: October 18, 2016
• First Posted (Estimate): October 20, 2016

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: July 5, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Neuritis; Optic Neuritis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Phenytoin
• Other Study ID Numbers: 9411257013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No