Clinical trial NCT02849457: Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberous Sclerosis Complex
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2016-07-29
Enrollment: 84
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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)

Primary outcomes:
measure: Cognitive Assessment Scores and Developmental Impact
timeFrame: 24 months
Secondary outcomes:
measure: Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.
timeFrame: 24 months
measure: Time to the Subject's First Clinical Seizure From Randomization
timeFrame: 24 months
measure: Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.
timeFrame: 24 months
measure: Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment
timeFrame: 12 months, 24 months and 36 months
measure: Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment
timeFrame: 24 months and 36 months
measure: Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events
timeFrame: 24 months
measure: EEG Biomarker for Developing Epilepsy
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Children's Hospital
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, PA
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati's Children Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: University of Alabama at Birmingham
name: Martina Bebin, MD, MPA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bebin EM, Peters JM, Porter BE, McPherson TO, O'Kelley S, Sahin M, Taub KS, Rajaraman R, Randle SC, McClintock WM, Koenig MK, Frost MD, Northrup HA, Werner K, Nolan DA, Wong M, Krefting JL, Biasini F, Peri K, Cutter G, Krueger DA; PREVeNT Study Group. Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial. Ann Neurol. 2023 Aug 28:10.1002/ana.26778. doi: 10.1002/ana.26778. Online ahead of print.
citation: 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.