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

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®)

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®)

Study Overview

• Status: Completed
• Conditions: Adult Refractory Complex Partial Seizures
• Intervention / Treatment: Drug: Sabril

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Medical Center
  • Delaware
    • Dover, Delaware, United States, 19901
      • CNMRI
  • Florida
    • Hollywood, Florida, United States, 33021-2834
      • Sunrise Clinical Research Group
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Peachtree Neurological Clinic
  • Idaho
    • Boise, Idaho, United States, 83702
      • Idaho Comprehensive Epilepsy Center
  • Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Minnesota
    • St. Paul, Minnesota, United States, 55102
      • Minnesota Epilepsy Group, PA
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10087
      • Columbia University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Neuroscience & Spine Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas
    • Lubbock, Texas, United States, 79410
      • Covenant Medical Group
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54308
      • Aurora BayCare Medical Center
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Important Inclusion Criteria:

1. The patient speaks English or Spanish.
2. The patient has had no prior exposure to Sabril.
3. To begin Sabril therapy for the treatment of CPS.
4. Male or female ≥18 years of age.

5. The patient has refractory CPS:

   1. 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.
   2. 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.
   3. The patient is taking at least 1 AED. A vagal nerve stimulator is not counted as an AED.
   4. The patient reports an average of 2 or more seizures per month averaged over the prior 3 months.
6. The patient is deemed by the treating neurologist and ophthalmologist to be able to reliably complete perimetry testing.
7. 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:

1. Prior exposure to Sabril.
2. 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.
3. Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity.
4. Concurrent use of an investigational agent or device or such use within 30 days of entering the study.
5. Concurrent use of the ketogenic or similar diet.
6. For any reason, the patient is considered by the investigator to be an unsuitable candidate for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sabril	Drug: Sabril; Sabril: 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.; Other Names: Vigabatrin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lundbeck LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: January 14, 2011
• First Submitted That Met QC Criteria: January 14, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Estimate): June 7, 2016
• Last Update Submitted That Met QC Criteria: April 28, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Epilepsy; Nervous System Diseases; Central Nervous System Diseases; Enzyme Inhibitors; Seizures; Neurologic Manifestations; Brain diseases; CPS; Vigabatrin-associated vision change; Adult refractory complex partial seizures; GABA Agents
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; GABA Agents; Anticonvulsants; Vigabatrin
• Other Study ID Numbers: 13098A