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NCT Number: NCT02849457

Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

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

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Key information

Conditions

Tuberous Sclerosis Complex Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hamartoma Heredodegenerative Disorders, Nervous System Malformations of Cortical Development Malformations of Cortical Development, Group I Neoplasms Neoplasms, Multiple Primary Neoplastic Syndromes, Hereditary Nervous System Diseases Nervous System Malformations Neurocutaneous Syndromes Neurodegenerative Diseases Tuberous Sclerosis

Age range

1 day–6 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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)

Treatment and study plan

Early Vigabatrin

Drug

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.

Other names: Sabril

Delayed Vigabatrin (Placebo)

Drug

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.

Primary outcomes

  1. Cognitive Assessment Scores and Developmental Impact

    Time frame: 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 outcomes

  1. Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.

    Time frame: 24 months

    Evaluate the number of subjects that develop seizures when treated with vigabatrin or placebo as a seizure prevention.

  2. Time to the Subject's First Clinical Seizure From Randomization

    Time frame: 24 months

    Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.

  3. Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.

    Time frame: 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).

  4. Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment

    Time frame: 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.

  5. Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment

    Time frame: 24 months and 36 months

    Evaluate ADOS2 scores and the impact of early versus late treatment at 24 and 36 months.

  6. Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events

    Time frame: 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.

  7. EEG Biomarker for Developing Epilepsy

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Martina Bebin

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex (PREVeNT Trial) A Randomized, Double-blind, Placebo-controlled Seizure Prevention Clinical Trial for Infants With TSC

Important dates

Study start
2016
Primary completion
2023
Study completion
2023
First posted
Jul 29, 2016
Registry last updated
Aug 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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