Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

• ClinicalTrials.gov Identifier: NCT02849457
• Recruitment Status: Completed
• First Posted: July 29, 2016
• Last Update Posted: May 9, 2023
• Sponsor: Martina Bebin
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Martina Bebin, University of Alabama at Birmingham

Study Description

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

Condition or disease	Intervention/treatment	Phase
Tuberous Sclerosis Complex	Drug: Vigabatrin; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official 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
• Study Start Date: December 2016
• Actual Primary Completion Date: April 26, 2023
• Actual Study Completion Date: May 5, 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Vigabatrin or Placebo; Vigabatrin or Placebo is given for administration, the entire content of one sachet (500 mg active drug) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID).	Drug: Vigabatrin; Subjects randomized to vigabatrin in Arm A 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 (Arm B) and continue to be followed until 36 months of age.; Other Name: Sabril; Drug: Placebo; Subjects randomized to placebo in Arm A 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 (Arm B) and continue to be followed until 36 months of age.
Vigabatrin; Vigabatrin open label is given for administration, the entire content of one sachet (500 mg active drug) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID).	Drug: Vigabatrin; Subjects randomized to vigabatrin in Arm A 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 (Arm B) and continue to be followed until 36 months of age.; Other Name: Sabril
No Intervention: Control Group; Enrolled subjects who never develop EEG abnormalities or clinical seizures

Outcome Measures

Primary Outcome Measures :

1. Cognitive Assessment Scores and Developmental Impact [ Time Frame: 24 months ]

   The primary outcome measure will be the cognitive assessment scores on the Bayley Scales of Infant and Toddler Development at 24 months.

   The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and compare the developmental impact of early versus delayed treatment with vigabatrin.

Secondary Outcome Measures :

1. Number of subjects that develop seizures when treated with vigabatrin [ Time Frame: 24 months ]
   Evaluate the number of subjects that develop seizures when treated with vigabatrin as a seizure prevention.
2. Time to the Subject's First Clinical Seizure [ Time Frame: 24 months ]
   Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.
3. Prevalence of Drug Resistant Epilepsy [ Time Frame: 24 months ]
   The prevalence of drug resistant epilepsy.
4. Evaluate Vineland II Scores and Impact of Early Versus Late Treatment [ Time Frame: 12 months, 24 months and 36 months ]
   Evaluate Vineland II scores and the impact of early versus late treatment with vigabatrin at 12, 24, and 36 months.
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

Eligibility Criteria

• Ages Eligible for Study: 1 Day to 6 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. less than or equal to 6 months of age
2. No history of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
3. 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:

1. Is greater than 6 months of age
2. Has not been diagnosed with TSC
3. History of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
4. Has received any anticonvulsant medication including vigabatrin, other anti-seizure therapeutic agent including cannabidiol
5. Has received an oral mTOR inhibitor such as everolimus or sirolimus
6. 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
7. Is currently enrolled, or plans on enrolling at any time during the duration of the study, in an experimental behavioral early intervention study
8. Has a history of being born prematurely (born less than <30 weeks gestation at the time of delivery)

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095

Stanford University

Palo Alto, California, United States, 94304

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02215

United States, Michigan

Beaumont Children's Hospital

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Minnesota Epilepsy Group, PA

Saint Paul, Minnesota, United States, 55102

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63110

United States, North Carolina

Duke University

Durham, North Carolina, United States, 37710

United States, Ohio

Cincinnati's Children Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

University of Texas Health Science Center at Houston

Houston, Texas, United States, 77054

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Martina Bebin

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Martina Bebin, MD, MPA; University of Alabama at Birmingham

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van der Poest Clement E, Jansen FE, Braun KPJ, Peters JM. Update on Drug Management of Refractory Epilepsy in Tuberous Sclerosis Complex. Paediatr Drugs. 2020 Feb;22(1):73-84. doi: 10.1007/s40272-019-00376-0.

• Responsible Party: Martina Bebin, Professor of Neurology and Pediatrics, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02849457
• Other Study ID Numbers: PREVeNT; 1U01NS092595-01A1 ( U.S. NIH Grant/Contract )
• First Posted: July 29, 2016
• Last Update Posted: May 9, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified data will be shared with National Database for Autism Research (NDAR)

Additional relevant MeSH terms:

Tuberous Sclerosis; Epilepsy; Sclerosis; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Vigabatrin; Anticonvulsants; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; GABA Agents; Neurotransmitter Agents; Physiological Effects of Drugs