Clinical trial NCT01278173: A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)
Official title: 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®)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adult Refractory Complex Partial Seizures
Keywords: 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
Lead sponsor: Lundbeck LLC
Sponsor class: INDUSTRY
First posted: 2011-01-17
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
timeFrame: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12
measure: Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
timeFrame: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: New Haven
country: United States
facility: Yale Medical Center
state: Connecticut
city: Dover
country: United States
facility: CNMRI
state: Delaware
city: Hollywood
country: United States
facility: Sunrise Clinical Research Group
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Peachtree Neurological Clinic
state: Georgia
city: Boise
country: United States
facility: Idaho Comprehensive Epilepsy Center
state: Idaho
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Lexington
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: St. Paul
country: United States
facility: Minnesota Epilepsy Group, PA
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Neuroscience & Spine Institute
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Lubbock
country: United States
facility: Covenant Medical Group
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: