## Protocol Section
### Identification Module
**NCT ID:** NCT01767779

**Brief Title:** Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

**Official Title:** Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

#### Organization Study ID Info
**ID:** 1P20NS080199-01
**Link:** https://reporter.nih.gov/quickSearch/1P20NS080199-01
**Type:** NIH
#### Organization
**Class:** OTHER
**Full Name:** University of Alabama at Birmingham
### Status Module
#### Completion Date
**Date:** 2018-12

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-04-11

**Type:** ACTUAL

**Last Update Submit Date:** 2019-04-09

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2016-12

**Type:** ACTUAL

#### Start Date
**Date:** 2012-09

**Status Verified Date:** 2019-04

#### Study First Post Date
**Date:** 2013-01-14
**Type:** ESTIMATED
**Study First Submit Date:** 2013-01-07
**Study First Submit QC Date:** 2013-01-10
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Children's Hospital Medical Center, Cincinnati

**Class:** OTHER

**Name:** The University of Texas Health Science Center, Houston

**Class:** OTHER

**Name:** University of California, Los Angeles

**Class:** OTHER

**Name:** Boston Children's Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Alabama at Birmingham

#### Responsible Party

**Investigator Affiliation:** University of Alabama at Birmingham

**Investigator Full Name:** Martina Bebin

**Investigator Title:** Associate Professor of Neurology

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Tuberous Sclerosis Complex

**Keywords:**

- Epilepsy

- TSC

- Tuberous Sclerosis Complex

- Infants

- Seizures

- Biomarkers

- EEG

### Design Module

#### Bio Spec

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

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC

**Label:** seizure free infants with dx of TSC

#### Arm Group 2

**Description:** 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.

**Label:** Parents or family guardian of cohort 1

### Outcomes Module

#### Primary Outcomes

**Description:** Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries.

**Measure:** Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex

**Time Frame:** 3 years

### Eligibility Module

**Eligibility 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

**Maximum Age:** 6 Months

**Minimum Age:** 1 Day

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

**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

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Birmingham

**Country:** United States

**Facility:** University of Alabama at Birmingham

**State:** Alabama

**Zip:** 35294

**Location 2:**

**City:** Los Angeles

**Country:** United States

**Facility:** UCLA

**State:** California

**Zip:** 90095

**Location 3:**

**City:** Boston

**Country:** United States

**Facility:** Boston Children's Hospital

**State:** Massachusetts

**Zip:** 02115

**Location 4:**

**City:** Cincinnati

**Country:** United States

**Facility:** Cincinnati Children's Hospital

**State:** Ohio

**Zip:** 45229

**Location 5:**

**City:** Houston

**Country:** United States

**Facility:** University of Texas in Houston

**State:** Texas

**Zip:** 77030

#### Overall Officials

**Official 1:**

**Affiliation:** University of Alabama at Birmingham

**Name:** Martina Bebin, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000006222

- Term: Hamartoma

- ID: D000009369

- Term: Neoplasms

- ID: D000009378

- Term: Neoplasms, Multiple Primary

- ID: D000009386

- Term: Neoplastic Syndromes, Hereditary

- ID: D000065703

- Term: Malformations of Cortical Development, Group I

- ID: D000054220

- Term: Malformations of Cortical Development

- ID: D000009421

- Term: Nervous System Malformations

- ID: D000020752

- Term: Neurocutaneous Syndromes

- ID: D000020271

- Term: Heredodegenerative Disorders, Nervous System

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M7983

- Name: Epilepsy

- Relevance: HIGH

- As Found: Epilepsy

- ID: M15452

- Name: Seizures

- Relevance: LOW

- As Found: Unknown

- ID: M17152

- Name: Tuberous Sclerosis

- Relevance: HIGH

- As Found: Tuberous Sclerosis

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9314

- Name: Hamartoma

- Relevance: LOW

- As Found: Unknown

- ID: M12323

- Name: Neoplasms, Multiple Primary

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12331

- Name: Neoplastic Syndromes, Hereditary

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M27589

- Name: Malformations of Cortical Development

- Relevance: LOW

- As Found: Unknown

- ID: M12365

- Name: Nervous System Malformations

- Relevance: LOW

- As Found: Unknown

- ID: M22509

- Name: Neurocutaneous Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M22092

- Name: Heredodegenerative Disorders, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T5751

- Name: Tuberous Sclerosis Complex

- Relevance: HIGH

- As Found: Tuberous Sclerosis Complex

### Condition Browse Module - Meshes

- ID: D000014402

- Term: Tuberous Sclerosis

- ID: D000004827

- Term: Epilepsy

- ID: D000012598

- Term: Sclerosis

### Misc Info Module

- Version Holder: 2024-05-24
