Neuroprotection With Phenytoin in Optic Neuritis

NCT01451593 | Completed Phase 2 DMC

• 1 other identifier: UCL/11/0083
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Optic Neuritis; Multiple Sclerosis

Keywords

Optic neuritis; Multiple sclerosis; Retinal nerve fibre layer; Axonal loss; Neuroprotection; Phenytoin; MRI; Optical coherence tomography; Sodium Channel Blockers

Outcome Measures

Primary Outcomes (1)

• Mean Retinal nerve fibre layer thickness

  The primary comparison will estimate active versus placebo mean retinal nerve fibre layer thickness of the retinal nerve fibre layer after 6 months, adjusted for the corresponding baseline measurement in the unaffected eye.

  Measured at entry and after 6 months

Secondary Outcomes (3)

• Visual function

  Measured at entry and 6 months

• Visual evoked potentials

  Measured at entry (or within 4 weeks) and after 6 months

• Optic 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

Study Arms (2)

phenytoin

EXPERIMENTAL

active arm of trial 1:1 allocation active versus placebo

Drug: Phenytoin

placebo

PLACEBO COMPARATOR

1:1 allocation active versus placebo

Drug: Placebo

Interventions

Phenytoin DRUG

Phenytoin will be loaded using at total dose of 15mg/kg (rounded to the nearest 100mg) divided into three equal doses given once daily for 3 days.This will be followed by a daily maintenance dose of 4mg/kg once a day (rounded up to the nearest 50mg, with a maximum dose of 300mg)for 13 weeks.Phenytoin levels will be taken at 1 and 3 months.

Also known as: Phenytoin sodium, Epanutin (Flynn Pharma)

phenytoin

Placebo DRUG

placebo identical in appearance to active IMP (phenytoin)

placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• National Multiple Sclerosis Society: collaborator
• Multiple Sclerosis Society of Great Britain and Northern Ireland: collaborator

Study Sites (2)

National Hospital for Neurology and Neurosurgery

London, WC1 3BG, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

Related Publications (3)

• Kodali S, Bianchi A, Raftopoulos R, Moccia M, Malladi AP, Yiannakas MC, Fugger M, Samson RS, Wheeler-Kingshott CAM, Koltzenburg M, Prados F, Hickman S, Kapoor R, Toosy AT. Effects of Phenytoin on the Retinal Ganglion Cell-Inner Plexiform Layer in Acute Optic Neuritis: Analysis of a Phase II Randomized Trial. Neurology. 2025 Oct 21;105(8):e213951. doi: 10.1212/WNL.0000000000213951. Epub 2025 Sep 25.

  PMID: 40997284 DERIVED

• 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: 10.1016/S1474-4422(16)00004-1. Epub 2016 Jan 26.

  PMID: 26822749 DERIVED

• 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.

  PMID: 24287594 DERIVED

MeSH Terms

Conditions

Optic Neuritis; Multiple Sclerosis

Interventions

Phenytoin

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Raju Kapoor, DM FRCP

  Institute of Neurology, University College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: October 13, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: March 1, 2015
• Last Updated: September 9, 2015

Record last verified: 2015-09

Locations

GB (2)