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

• Sponsor: Tehran University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02939937
• Collaborator: (none)
• Enrollment: 71
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.8
• Patients Per Site Per Month: 3.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Optic Neuritis	Drug: Phenytoin; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: participant , investigator
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Mar 9, 2017
• Actual Primary Completion Date: Nov 11, 2018
• Actual Study Completion Date: Jan 2, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

2. Macular Layer Thickness [Measured at baseline and month 1, 6]

   macular layer thickness measure in 8 sectors by Heidelberg spectral domain Optical Coherence Tomography

3. 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.

4. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eye Research Center Farabi Hosoital	Tehran		Iran, Islamic Republic of	3542168325

Sponsors and Collaborators

• Tehran University of Medical Sciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 14, 2019
• Informed Consent Form - Apr 15, 2019
• Statistical Analysis Plan - Jul 5, 2019

More Information

Publications

None provided.

• Responsible Party: Tehran University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT02939937
• Other Study ID Numbers: 9411257013
• First Posted: Oct 20, 2016
• Last Update Posted: Aug 12, 2019
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuritis; Optic Neuritis; Phenytoin

Study Results

Participant Flow

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	21	50
COMPLETED	15	47
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Phenytoin	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	21	50	71
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	50 100%	71 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	14 66.7%	40 80%	54 76.1%
Male	7 33.3%	10 20%	17 23.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Iran	15 71.4%	47 94%	62 87.3%

Outcome Measures

1. Primary Outcome

Title	Retinal Ganglion Cell Inner Plexiform Layer Thickness
Description	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

Outcome Measure Data

Analysis Population Description

incomplete follow up from baseline to 6 month

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Measure Participants	15	47
baseline	36.56 (6.61)	34.65 (8.49)
1 month	31 (6.61)	29.42 (5.98)
6 months	30.70 (5.56)	32.12 (9.10)

2. Primary Outcome

Title	Macular Layer Thickness
Description	macular layer thickness measure in 8 sectors by Heidelberg spectral domain Optical Coherence Tomography
Time Frame	Measured at baseline and month 1, 6

Outcome Measure Data

Analysis Population Description

incomplete follow up

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Measure Participants	15	47
baseline	262.73 (22.02)	265.98 (22.5)
1 month	255 (19.72)	264.39 (22.53)
6 months	269 (28.29)	268.37 (22.69)

3. Primary Outcome

Title	Best Corrected Visual Acuity
Description	Best corrected visual acuity is converted to logMAR (logarithms of minimum angle of resolution) by statistical calculation.
Time Frame	at baseline and month 6

Outcome Measure Data

Analysis Population Description

incomplete follow up

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Measure Participants	15	47
baseline	1.44 (0.98)	1 (0.83)
6 months	0.04 (0.067)	0.13 (0.448)

4. Primary Outcome

Title	Visual Field Mean Deviation in Decibel
Description	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

Outcome Measure Data

Analysis Population Description

incomplete follow up

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Measure Participants	15	47
Baseline visual field mean deviation (MD)	-17.07 (11.41)	-17.76 (11.81)
6 months MD	-3.89 (4.46)	-5.16 (7.49)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

incomplete follow up

Arm/Group Title	Phenytoin	Placebo
Arm/Group Description	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.	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.
Measure Participants	15	47
Baseline	131.8 (36.56)	124.87 (47.51)
1 month	93.85 (8.64)	97.41 (23)
6 months	77.7 (20.03)	78.61 (18.97)

Adverse Events

Time Frame	6 months
Arm/Group Title	Phenytoin		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Phenytoin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/50 (0%)
Serious Adverse Events
	Phenytoin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/50 (0%)
Skin and subcutaneous tissue disorders
steven johnson	1/21 (4.8%)	1	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	Phenytoin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		0/50 (0%)
Skin and subcutaneous tissue disorders
skin reaction	4/21 (19%)	4	0/50 (0%)	0

Limitations/Caveats

Shorter follow up Poor compliance for oral drug intake

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.