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Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

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ClinicalTrials.gov Identifier: NCT02849457
Recruitment Status : Active, not recruiting
First Posted : July 29, 2016
Last Update Posted : April 22, 2020
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Martina Bebin, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE July 13, 2016
First Posted Date  ICMJE July 29, 2016
Last Update Posted Date April 22, 2020
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
  • 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.
  • 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.
  • Prevalence of Drug Resistant Epilepsy [ Time Frame: 24 months ]
    The prevalence of drug resistant epilepsy.
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Tuberous Sclerosis Complex
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Vigabatrin
    • Drug: Placebo
  • 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).
    Intervention: Drug: Vigabatrin
  • No Intervention: Control Group
    Enrolled subjects who never develop EEG abnormalities or clinical seizures
Publications * 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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 21, 2020)
84
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2016)
80
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02849457
Other Study ID Numbers  ICMJE PREVeNT
1U01NS092595-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified data will be shared with National Database for Autism Research (NDAR)
Responsible Party Martina Bebin, University of Alabama at Birmingham
Study Sponsor  ICMJE Martina Bebin
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Martina Bebin, MD, MPA University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP