Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

NCT02849457 | Completed Phase 2 Results DMC

• 2 other identifiers: PREVeNT1U01NS092595-01A1
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 13

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

Conditions

Tuberous Sclerosis Complex

Outcome Measures

Primary Outcomes (1)

• Cognitive Assessment Scores and Developmental Impact

  The primary outcome measure will be the standardized Cognitive scale scores on the Bayley Scales of Infant and Toddler Development- Third Edition at 24 months. The Cognitive scale Composite score is a standard score derived from the observed and elicited performance of the child on cognitive assessment tasks, with a mean of 100 and standard deviation of 10. The range for the Cognitive scale Composite score is 55 to 145. The score is calculated using standard procedures available in the manual for this measure. A higher score is considered better performance. The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and to compare the developmental impact of early versus delayed treatment with vigabatrin.

  24 months

Secondary Outcomes (7)

• Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.

  24 months

• Time to the Subject's First Clinical Seizure From Randomization

  24 months

• Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.

  24 months

• Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment

  12 months, 24 months and 36 months

• Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment

  24 months and 36 months

Study Arms (3)

Delayed Vigabatrin (Placebo)

PLACEBO COMPARATOR

Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo 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 placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Drug: Early Vigabatrin; Drug: Delayed Vigabatrin (Placebo)

Early Vigabatrin

EXPERIMENTAL

Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with vigabatrin 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 vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Drug: Early Vigabatrin

Watchful Waiting (Control Group)

NO INTERVENTION

Enrolled participants in this arm are those who never develop EEG abnormalities or clinical seizures during the length of the study. While all participants who enrolled in the study started in this group, participants were randomized upon development of EEG epileptiform activity. All participants who completed the study without developing EEG epileptiform activity or clinical seizures are reported in this group.

Interventions

Early Vigabatrin DRUG

Subjects randomized to vigabatrin 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 and continue to be followed until 36 months of age.

Also known as: Sabril

Delayed Vigabatrin (Placebo); Early Vigabatrin

Delayed Vigabatrin (Placebo) DRUG

Subjects randomized to placebo 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 and continue to be followed until 36 months of age.

Delayed Vigabatrin (Placebo)

Eligibility Criteria

• Age: 1 Day - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Martina Bebin: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Beaumont Children's Hospital

Royal Oak, Michigan, 48073, United States

Location

Minnesota Epilepsy Group, PA

Saint Paul, Minnesota, 55102, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Duke University

Durham, North Carolina, 37710, United States

Location

Cincinnati's Children Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77054, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (2)

• 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.

  PMID: 37638552 RESULT

• 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.

  PMID: 31912454 DERIVED

MeSH Terms

Conditions

Tuberous Sclerosis

Interventions

Vigabatrin

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

COVID-19 impacted one of the secondary endpoints (ADOS2) because of the requirement for facemasks during the assessment which would invalidate the ADOS2. Therefore this secondary outcome measure abandoned.

Results Point of Contact

• Title: E. Martina Bebin M.D., M.P.A.
• Organization: University of Alabama at Birmingham

ebebin@uabmc.edu

205-975-2890

Study Officials

• Martina Bebin, MD, MPA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology and Pediatrics

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 29, 2016
• Study Start: December 1, 2016
• Primary Completion: April 26, 2023
• Study Completion: May 5, 2023
• Last Updated: August 19, 2024
• Results First Posted: August 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

US (13)