Study design is a Phase IIb prospective multi-center, randomized, placebo-controlled, double-blind clinical trial. The goal will be to enroll 80 infants with Tuberous Sclerosis Complex who are less than 6 months of age prior to the onset of their first seizure
The central hypothesis of this Phase IIb trial is that early identification of electroencephalography (EEG) biomarkers and early treatment versus delayed treatment with vigabatrin in infants with tuberous sclerosis complex (TSC) will have a positive impact on developmental outcomes at 24 months of age. It would also prevent or lower the risk of developing infantile spasms and refractory seizures. This preventative approach would be expected to result in more favorable long-term cognitive, behavioral, developmental and psychiatric outcomes and significantly improve overall quality of life. It is a randomized, double-blind, placebo-controlled clinical trial design. Successful completion of this trial will also advance the field by demonstrating the value of systematic surveillance with EEG in asymptomatic infants with TSC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
84
Subjects randomized to vigabatrin will be treated with vigabatrin 100mg/kg/day until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on study drug, they will transition into the Open label phase of the study and continue to be followed until 36 months of age.
Subjects randomized to placebo will be treated with matching placebo at 100mg/kg/day until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on study drug, they will transition into the Open label phase of the study and continue to be followed until 36 months of age.
University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California, Los Angeles
Los Angeles, California, United States
Stanford University
Palo Alto, California, United States
Cognitive Assessment Scores and Developmental Impact
The primary outcome measure will be the standardized Cognitive scale scores on the Bayley Scales of Infant and Toddler Development- Third Edition at 24 months. The Cognitive scale Composite score is a standard score derived from the observed and elicited performance of the child on cognitive assessment tasks, with a mean of 100 and standard deviation of 10. The range for the Cognitive scale Composite score is 55 to 145. The score is calculated using standard procedures available in the manual for this measure. A higher score is considered better performance. The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and to compare the developmental impact of early versus delayed treatment with vigabatrin.
Time frame: 24 months
Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.
Evaluate the number of subjects that develop seizures when treated with vigabatrin or placebo as a seizure prevention.
Time frame: 24 months
Time to the Subject's First Clinical Seizure From Randomization
Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.
Time frame: 24 months
Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.
The count of participants with drug resistant epilepsy. Drug resistant epilepsy classified according to International League Against Epilepsy (ILAE) definition, specifically defined as any participant on 2 or more anti-seizure medications experiencing persistent seizures (seizures occurring within 3 months of the 24 month participant visit).
Time frame: 24 months
Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment
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Children's National Medical Center
Washington D.C., District of Columbia, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Beaumont Children's Hospital
Royal Oak, Michigan, United States
Minnesota Epilepsy Group, PA
Saint Paul, Minnesota, United States
Washington University in St. Louis
St Louis, Missouri, United States
Duke University
Durham, North Carolina, United States
Cincinnati's Children Hospital Medical Center
Cincinnati, Ohio, United States
...and 3 more locations
The range for the Vineland-II Adaptive Behavior Composite is 20 to 160 The Vineland-II ABC standard score has a mean of 100 and standard deviation of 15, with higher scores indicating better overall adaptive functioning. The ABC standard score is a composite derived from obtained scores on the Communication, Daily Living Skills, Socialization, and Motor Skills domains on the Vineland-II and is calculated according to standardized procedures described in the Vineland-II manual.
Time frame: 12 months, 24 months and 36 months
Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment
Evaluate ADOS2 scores and the impact of early versus late treatment at 24 and 36 months.
Time frame: 24 months and 36 months
Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events
Number of subjects with vigabatrin related adverse events, severe adverse events as assessed by CTCAE v4.0 and risk evaluation and mitigation strategy (REMS) measures as required by the FDA.
Time frame: 24 months
EEG Biomarker for Developing Epilepsy
Feasibility of the routine 1 hour video EEG in determining the EEG biomarker for developing epilepsy. Outcome was determined as the number of participants developing seizures amongst those developing the biomarker (epileptiform activity).
Time frame: 24 months