Tuberous Sclerosis ComplexNCT01767779
Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC
An observational study of Tuberous Sclerosis Complex, run by University of Alabama at Birmingham at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 6 months
- Conditions the study is for
- Tuberous Sclerosis Complex
- How many people
- 40 participants
- Where
- 5 sitesUnited States
- Study dates
- Sep 2012to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 6 months
- All sexes
- No healthy volunteers
- 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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
University of Texas in Houston
Houston, Texas, 77030
UCLA
Los Angeles, California, 90095
About this study
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.
Read the 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
- Tuberous Sclerosis Complex
- Keywords
- Epilepsy, TSC, Tuberous Sclerosis Complex, Infants, Seizures, Biomarkers, EEG
- Medical subject headings
- Tuberous Sclerosis, Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex
Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2013 (estimated)
- Study startSep 2012
- Primary completionDec 2016
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberous Sclerosis ComplexStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, The University of Texas Health Science Center, Houston, University of California, Los Angeles, Boston Children's Hospital
- Responsible party
- Principal investigator, Martina Bebin, University of Alabama at Birmingham
- Investigators
- Martina Bebin, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01767779
- Sponsor's protocol ID
- 1P20NS080199-01
- Status last verified
- Apr 2019
- First submitted
- 7 Jan 2013
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Sadeghzadeh S, Johnstone TM, Peters JM, Porter BE, Ihnen SKZ. Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex. J Neurosurg Pediatr. 2024 Jul 12;34(4):384-392. doi: 10.3171/2024.4.PEDS2481. Print 2024 Oct 1.
PubMed 38996393
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC
- ClinicalTrials.gov ID
- NCT01767779
- Acronym / sponsor ID
- 1P20NS080199-01
- Conditions
- Tuberous Sclerosis Complex
- Keywords
- Epilepsy, TSC, Tuberous Sclerosis Complex, Infants, Seizures, Biomarkers, EEG
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, The University of Texas Health Science Center, Houston, University of California, Los Angeles, Boston Children's Hospital
- Study start
- Sep 2012
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 14 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 1 day to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex
Time frame: 3 years
Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2019.
- Derived from this study: PubMed 38996393Sadeghzadeh S, Johnstone TM, Peters JM, Porter BE, Ihnen SKZ. Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex. J Neurosurg Pediatr. 2024 Jul 12;34(4):384-392. doi: 10.3171/2024.4.PEDS2481. Print 2024 Oct 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martina Bebin, MD principal investigator
University of Alabama at Birmingham
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberous Sclerosis Complex, run by University of Alabama at Birmingham at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01767779, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2019.