Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

Sponsor

Martina Bebin (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02849457

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Enrollment

Locations

Arms

76.9

Duration (Months)

6.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Dec 1, 2016

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 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 Names: 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.
Other: 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 Names: Sabril
No Intervention: Control Group Enrolled subjects who never develop EEG abnormalities or clinical seizures

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 Names:

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.

Other: 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

Other Names:

Sabril

No Intervention: Control Group

Enrolled subjects who never develop EEG abnormalities or clinical seizures

Outcome Measures

Primary Outcome Measures

Cognitive Assessment Scores and Developmental Impact [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

Number of subjects that develop seizures when treated with vigabatrin [24 months]
Evaluate the number of subjects that develop seizures when treated with vigabatrin as a seizure prevention.
Time to the Subject's First Clinical Seizure [24 months]
Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.
Prevalence of Drug Resistant Epilepsy [24 months]
The prevalence of drug resistant epilepsy.
Evaluate Vineland II Scores and Impact of Early Versus Late Treatment [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.
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 6 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	Stanford University	Palo Alto	California	United States	94304
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	Boston Children's Hospital	Boston	Massachusetts	United States	02215
6	Beaumont Children's Hospital	Royal Oak	Michigan	United States	48073
7	Minnesota Epilepsy Group, PA	Saint Paul	Minnesota	United States	55102
8	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
9	Duke University	Durham	North Carolina	United States	37710
10	Cincinnati's Children Hospital Medical Center	Cincinnati	Ohio	United States	45229
11	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
12	University of Texas Health Science Center at Houston	Houston	Texas	United States	77054
13	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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

First Posted:

Jul 29, 2016

Last Update Posted:

May 6, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Study Results

No Results Posted as of May 6, 2022