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Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

Primary Purpose

Tuberous Sclerosis Complex

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vigabatrin
Placebo
Sponsored by
Martina Bebin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberous Sclerosis Complex

Eligibility Criteria

1 Day - 6 Months (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Alabama at Birmingham
  • University of California, Los Angeles
  • Stanford University
  • Children's National Medical Center
  • Boston Children's Hospital
  • Beaumont Children's Hospital
  • Minnesota Epilepsy Group, PA
  • Washington University in St. Louis
  • Duke University
  • Cincinnati's Children Hospital Medical Center
  • The Children's Hospital of Philadelphia
  • University of Texas Health Science Center at Houston
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Other

No Intervention

Arm Label

Vigabatrin or Placebo

Vigabatrin

Control Group

Arm Description

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).

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).

Enrolled subjects who never develop EEG abnormalities or clinical seizures

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Prevalence of Drug Resistant Epilepsy
The prevalence of drug resistant epilepsy.
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.
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.
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.
EEG Biomarker for Developing Epilepsy
Feasibility of the routine 1 hour video EEG in determining the EEG biomarker for developing epilepsy

Full Information

First Posted
July 13, 2016
Last Updated
May 6, 2023
Sponsor
Martina Bebin
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT02849457
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
December 2016 (undefined)
Primary Completion Date
April 26, 2023 (Actual)
Study Completion Date
May 5, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Martina Bebin
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis Complex

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vigabatrin or Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Vigabatrin
Arm Type
Other
Arm Description
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).
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Enrolled subjects who never develop EEG abnormalities or clinical seizures
Intervention Type
Drug
Intervention Name(s)
Vigabatrin
Other Intervention Name(s)
Sabril
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cognitive Assessment Scores and Developmental Impact
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Number of subjects that develop seizures when treated with vigabatrin
Description
Evaluate the number of subjects that develop seizures when treated with vigabatrin as a seizure prevention.
Time Frame
24 months
Title
Time to the Subject's First Clinical Seizure
Description
Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.
Time Frame
24 months
Title
Prevalence of Drug Resistant Epilepsy
Description
The prevalence of drug resistant epilepsy.
Time Frame
24 months
Title
Evaluate Vineland II Scores and Impact of Early Versus Late Treatment
Description
Evaluate Vineland II scores and the impact of early versus late treatment with vigabatrin at 12, 24, and 36 months.
Time Frame
12 months, 24 months and 36 months
Title
Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment
Description
Evaluate ADOS2 scores and the impact of early versus late treatment at 24 and 36 months.
Time Frame
24 months and 36 months
Title
Number of Subjects with Vigabatrin Related Adverse Events and Severe Adverse Events
Description
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.
Time Frame
24 months
Title
EEG Biomarker for Developing Epilepsy
Description
Feasibility of the routine 1 hour video EEG in determining the EEG biomarker for developing epilepsy
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martina Bebin, MD, MPA
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beaumont Children's Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Minnesota Epilepsy Group, PA
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
37710
Country
United States
Facility Name
Cincinnati's Children Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data will be shared with National Database for Autism Research (NDAR)
Citations:
PubMed Identifier
31912454
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.
Results Reference
derived

Learn more about this trial

Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

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