A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the change in visual fields by means of automated static perimetry and to evaluate the change in retinal structure by means of spectral domain optical coherence tomography (SD-OCT) in adult patients with refractory complex partial seizures (CPS) being treated with vigabatrin (Sabril®)

Detailed Description
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Multicenter, prospective open-label study with approximately 25 sites in the US that specialize in caring for adult patients with refractory CPS Sites must have access to Humphrey static perimetry and to Spectralis SD-OCT. All vision test results will be sent to the central readers for evaluation. Additional study tests: The Columbia Suicide Severity Rating Scale (C-SSRS) The National Eye Institute Visual Field Questionnaire-39 (NEI VFQ-39) A whole blood sample for specific analysis of DNA characteristics An optional whole blood sample for exploratory analysis of DNA characteristics Plasma samples for bioanalytical analysis of vigabatrin and blood samples for taurine biomarker analysis

Official Title
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A Prospective, Open-label Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)

Conditions
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Adult Refractory Complex Partial Seizures

Intervention / Treatment
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* Drug: Sabril


Participation Criteria
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Eligibility Criteria
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Important Inclusion Criteria: The patient speaks English or Spanish. The patient has had no prior exposure to Sabril. To begin Sabril therapy for the treatment of CPS. Male or female ≥18 years of age. The patient has refractory CPS: The patient has complex partial epilepsy of more than 1 year duration and no other seizure type within the past year except for partial seizures secondarily generalized. The patient has failed because of lack of efficacy 3 or more prior or concurrent treatment trials including 3 or more anti-epileptic drugs (AEDs) of differing pharmacologic mechanisms administered as monotherapy or polytherapy. The patient is taking at least 1 AED. A vagal nerve stimulator is not counted as an AED. The patient reports an average of 2 or more seizures per month averaged over the prior 3 months. The patient is deemed by the treating neurologist and ophthalmologist to be able to reliably complete perimetry testing. The initial (Visit 1) SD-OCT and static perimetry readings tests must be performed and assessed for technical adequacy by the SD-OCT and perimetry central readers prior to the first dose of Sabril. The initial (Visit 1) tangent corner test must be performed prior to the first dose of Sabril. Exclusion Criteria: Prior exposure to Sabril. Pre-existing ocular or neurological disease that might affect bilateral visual fields or interfere with perimetry (e.g., aphakia, visually significant cataract, glaucoma, diabetes mellitus, ischemic optic neuropathy, multiple sclerosis). Patients with stable visual field defects from CNS lesions (e.g., epilepsy surgery more than 6 months prior to receiving Sabril) may be enrolled. Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity. Concurrent use of an investigational agent or device or such use within 30 days of entering the study. Concurrent use of the ketogenic or similar diet. For any reason, the patient is considered by the investigator to be an unsuitable candidate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sabril<br> | Drug: Sabril<br>* Sabril: 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.<br>* Other names: Vigabatrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB) | Mean change from the reference value in 30-2 SITA mean deviation, which was generated using the University of Iowa Visual Field Reading Center (VFRC) normative database and the Humphrey Field Analyzer (HFA) normative database. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). The mean change from the reference value are presented for Months 3, 6, 9 and 12. A negative change from the reference value indicates a decrease in the central visual field. | Baseline (Month 0), Month 3, Month 6, Month 9, Month 12 | 
| Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography) | Mean change from the reference value in average RNFL thickness (µm) as measured by SD-OCT. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). Thinning of the RNFL, that is, a negative change from the reference value, has been associated with ophthalmological disease. | Baseline (Month 0), Month 3, Month 6, Month 9, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vigabatrin-associated vision change, Adult refractory complex partial seizures, CPS, Epilepsy, Seizures, Brain diseases, Central Nervous System Diseases, Nervous System Diseases, Neurologic Manifestations, Enzyme Inhibitors, GABA Agents