Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

Tuberous Sclerosis Complex Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02849457
• Other study ID #: PREVeNT
• Secondary ID: 1U01NS092595-01A
• Status: Completed
• Phase: Phase 2
• Start date: December 2016
• Est. completion date: May 5, 2023

Study information

• Verified date: May 2023
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: May 5, 2023
• Est. primary completion date: April 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 6 Months

Eligibility

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)

Related Conditions & MeSH terms

• Epilepsy
• Sclerosis
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati's Children Hospital Medical Center	Cincinnati	Ohio
United States	Duke University	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	Stanford University	Palo Alto	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Beaumont Children's Hospital	Royal Oak	Michigan
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Minnesota Epilepsy Group, PA	Saint Paul	Minnesota
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Martina Bebin	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Assessment Scores and Developmental Impact	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.	24 months
Secondary	Number of subjects that develop seizures when treated with vigabatrin	Evaluate the number of subjects that develop seizures when treated with vigabatrin as a seizure prevention.	24 months
Secondary	Time to the Subject's First Clinical Seizure	Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.	24 months
Secondary	Prevalence of Drug Resistant Epilepsy	The prevalence of drug resistant epilepsy.	24 months
Secondary	Evaluate Vineland II Scores and Impact of Early Versus Late Treatment	Evaluate Vineland II scores and the impact of early versus late treatment with vigabatrin at 12, 24, and 36 months.	12 months, 24 months and 36 months
Secondary	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.	24 months and 36 months
Secondary	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.	24 months
Secondary	EEG Biomarker for Developing Epilepsy	Feasibility of the routine 1 hour video EEG in determining the EEG biomarker for developing epilepsy	24 months