Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex

NCT ID: NCT02849457

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2023-05-05

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.

Conditions

Tuberous Sclerosis Complex

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Delayed Vigabatrin (Placebo)

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.

Group Type: PLACEBO_COMPARATOR

Early Vigabatrin

Intervention Type: 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.

Delayed Vigabatrin (Placebo)

Intervention Type: 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.

Early Vigabatrin

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.

Group Type: EXPERIMENTAL

Early Vigabatrin

Intervention Type: 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.

Watchful Waiting (Control Group)

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Early Vigabatrin

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.

Intervention Type: DRUG

Delayed Vigabatrin (Placebo)

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.

Intervention Type: DRUG

Other Intervention Names

Sabril

Eligibility Criteria

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)

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Martina Bebin

OTHER

Sponsor Role: lead

Responsible Party

Martina Bebin

Professor of Neurology and Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Martina Bebin, MD, MPA

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California, Los Angeles

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

Children's National Medical Center

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

Boston Children's Hospital

Boston, Massachusetts, United States

Beaumont Children's Hospital

Royal Oak, Michigan, United States

Minnesota Epilepsy Group, PA

Saint Paul, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

Duke University

Durham, North Carolina, United States

Cincinnati's Children Hospital Medical Center

Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 37638552 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31912454 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1U01NS092595-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PREVeNT

Identifier Type: -

Identifier Source: org_study_id