Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Children's Hospital Medical Center, Cincinnati
The University of Texas Health Science Center, Houston
University of California, Los Angeles
Children's Hospital Boston
Information provided by (Responsible Party):
Martina Bebin, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01767779
First received: January 7, 2013
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

To determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial. Since not all patients with TSC develop epilepsy, it would be useful to have a biomarker that could predict those patients destined to have epilepsy and thus identify those TSC patients most appropriate for an antiepileptogenic drug trial. A recent study suggests that treating TSC patients with an abnormal EEG prior to onset of infantile spasms with vigabatrin may improve neurological outcome, but the use of EEG as a reliable biomarker of future epilepsy has not been rigorously validated. In this specific aim, we will test the reliability of EEG in predicting future development of infantile spasms or epilepsy in TSC patients during the first year of life.


Condition
Tuberous Sclerosis Complex

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries.


Biospecimen Retention:   Samples With DNA

A single venous blood sample will be drawn from the child and parents/family guardian for future research studies and future genetic testing


Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
seizure free infants with dx of TSC
infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC
Parents or family guardian of cohort 1
Parent or family guardian of infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC.

Detailed Description:

Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there have been tremendous interest and effort by basic scientists and clinicians in epilepsy in developing disease-modifying or "antiepileptogenic" therapies. However, these efforts are hindered by a couple significant limitations: 1) difficulty in identifying an appropriate high-risk patient population in which a preventative approach is feasible and justifiable, and 2) lack of appropriate drug targets with antiepileptogenic properties. Tuberous Sclerosis Complex (TSC) is one of the most common genetic causes of epilepsy and a subset of TSC patients may represent a rational, feasible population to target with an antiepileptogenic approach for several reasons. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to non-neurological findings - thus, it is feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy (~80%) in the future, including infantile spasms (~35%), a particularly devastating type of childhood epilepsy with a poor prognosis - thus, initiating a therapy with potential side effects in a pre-symptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC, as already supported by pre-clinical animal studies - thus, a rational mechanistically-based treatment potentially already exists and can be readily tested in TSC patients. However, there may be significant risks and side effects of mTOR inhibitors, especially during early childhood, such as chronic immunosuppression and theoretical effects on learning, growth, and development. Thus, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors.

The aim of this clinical trial is to determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial.

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC (determined as standard of care); parent/family guardian health status is unknown

Criteria

Inclusion Criteria:

Cohort 1

  • < 6 months of age; Seizure free at the time of study enrollment; and meets genetic or clinical diagnostic criteria for TSC (Tuberous Sclerosis), the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, echocardiogram.

Cohort 2

  • Parent or family guardian of infant

Exclusion Criteria:

Cohort 1

  • ≥ 6months of age; history of seizures and/or infantile spasms; patients receiving vigabatrin or any anti-epileptic medication or mTOR inhibitor prior to study enrollment Cohort 2
  • not parent or family guardian
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767779

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCLA
Los Angeles, California, United States, 90095
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas in Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
University of Alabama at Birmingham
Children's Hospital Medical Center, Cincinnati
The University of Texas Health Science Center, Houston
University of California, Los Angeles
Children's Hospital Boston
Investigators
Principal Investigator: Martina Bebin, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Martina Bebin, Associate Professor of Neurology, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01767779     History of Changes
Other Study ID Numbers: 1P20NS080199-01
Study First Received: January 7, 2013
Last Updated: June 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Epilepsy
TSC
Tuberous Sclerosis Complex
Infants
Seizures
Biomarkers
EEG

Additional relevant MeSH terms:
Sclerosis
Epilepsy
Tuberous Sclerosis
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development
Nervous System Malformations
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 22, 2014