Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex
- Conditions
- Tuberous Sclerosis Complex
- Interventions
- Registration Number
- NCT02849457
- Lead Sponsor
- Martina Bebin
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
- less than or equal to 6 months of age
- No history of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
- Meet genetic or clinical diagnostic criteria for TSC, the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, echocardiogram
- Is greater than 6 months of age
- Has not been diagnosed with TSC
- History of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
- Has received any anticonvulsant medication including vigabatrin, other anti-seizure therapeutic agent including cannabidiol
- Has received an oral mTOR inhibitor such as everolimus or sirolimus
- Has taken an investigational drug, including but not limited to cannabidiol, as part of a research study 30 days prior to enrollment, or plans on taking an investigational drug at any time during the duration of the study
- Is currently enrolled, or plans on enrolling at any time during the duration of the study, in an experimental behavioral early intervention study
- Has a history of being born prematurely (born less than <30 weeks gestation at the time of delivery)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Delayed Vigabatrin (Placebo) Early Vigabatrin Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo 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 placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age. Delayed Vigabatrin (Placebo) Delayed Vigabatrin (Placebo) Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo 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 placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age. Early Vigabatrin Early Vigabatrin Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with vigabatrin 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 vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
- Primary Outcome Measures
Name Time Method Cognitive Assessment Scores and Developmental Impact 24 months 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.
- Secondary Outcome Measures
Name Time Method Count of Participants With Drug Resistant Epilepsy at 24 Months of Age. 24 months 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).
Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment 12 months, 24 months and 36 months 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.Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study. 24 months Evaluate the number of subjects that develop seizures when treated with vigabatrin or placebo as a seizure prevention.
Time to the Subject's First Clinical Seizure From Randomization 24 months Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.
Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events 24 months 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.
EEG Biomarker for Developing Epilepsy 24 months 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).
Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment 24 months and 36 months Evaluate ADOS2 scores and the impact of early versus late treatment at 24 and 36 months.
Trial Locations
- Locations (13)
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
Children's National Medical Center
🇺🇸Washington, 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
🇺🇸Saint Louis, Missouri, United States
Duke University
🇺🇸Durham, North Carolina, United States
Cincinnati's Children Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Scroll for more (3 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States