Benign Childhood Epilepsy With Centro-Temporal SpikesPhase 1FIRSTNCT01521130
Imaging the Effect of Centrotemporal Spikes and Seizures on Language in Children
A Phase 1 study testing Levetiracetam in people with Benign Childhood Epilepsy With Centro-Temporal Spikes, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
This project examines how seizures, and abnormal brain activity, affect language skill in children with Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS). BECTS is a common type of childhood epilepsy, and while BECTS patients stop having seizures by their late teenage years, many studies have shown that… Read more about this study
- Who is it for?
- Ages 5 to 13 yearsHealthy volunteers can take part
- Conditions the study is for
- Benign Childhood Epilepsy With Centro-Temporal Spikes
- What is being tested?
- Levetiracetam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Jul 2017
- Phase
- Phase 1
- 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 5 to 13 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Diagnosis: Child has newly diagnosed BECTS according to International League Against Epilepsy (ILAE) criteria (including normal EEG background for age, at least 1 partial onset seizure, and unilateral or bilateral central/mid-temporal sharp waves with a positive horizontal dipole).
- Age: The child's age is between 5 years, 0 months and 13 years, 11 months at study entry.
- Language: The child must be a monolingual native speaker of English.
- Handedness : The child must be right-handed.
- Females: females of child bearing potential must agree to an acceptable and non-systemic form of birth control (including abstinence).
- Intelligence: The child must have clinician-judged normal intelligence.
Show all 23Show fewer
- Academic History: The child must have an academic history of a regular education program (i.e., not in a special education class or program) without repeating grades.
- Parent/Guardians:
- The patient's parent/guardian must be able to keep an accurate seizure record.
- Informed consent from the child's parent or legal guardian.
- Parents (guardians) must be able and willing to comply with instructions and study procedures.
- Assent: Assent from the child if age 11 years or older.
- Demographic characteristics: Children will be between 7 and < 14 years old at the time of enrollment. Children of both sexes and all race/ethnicities will be enrolled.
- Language: The child must be a monolingual native speaker of English.
- Handedness: The child must be right-handed.
- Females: Females of child bearing potential must agree to an acceptable and non-systemic form of birth control (including abstinence).
- Intelligence: The child must have clinician-judged normal intelligence.
- Academic History: The child must have an academic history of a regular education program (i.e., not in a special education class or program) without repeating grades.
- Parents/Guardians:
- Informed consent from the child's parent or legal guardian.
- Parents (guardians) must be able and willing to comply with instructions and study procedures.
- Assent: Assent from the child if age 11 years or older.
- Demographic characteristics: Children will be between 5 and < 14 years old at the time of enrollment. Children of both sexes will be enrolled and no child will be excluded on the basis of race/ethnicity.
Who cannot join
- Clinical Contraindications
- Children with diagnosis of Benign Occipital Epilepsy (BOE - normal EEG background, and unilateral or bilateral occipital sharp waves activated by eye closure).
- Children with history of primary generalized seizures (absence, myoclonic, drop).
- Children with mixed seizure disorder (e.g., Lennox-Gastaut Syndrome).
- Children sensory seizures only (i.e., auras).
- Children with diagnoses of pervasive developmental disorders (e.g., autism/autism spectrum disorders).
Show all 35Show fewer
- Children with progressive neurological disease (e.g., degenerative, progressive neoplasm).
- Children with major medical disease (e.g., IDDM, depression, suicide attempt. cancer, renal failure).
- Children with a history of neonatal seizures.
- Pregnancy: Children who are pregnant will not be eligible for enrollment.
- Prior Therapy
- Children previously or currently treated with an AED for any reason (other than non chronic benzodiazepine, e.g., ED treatment).
- Children taking any psychoactive agent other than psychostimulants for ADD/ADHD.
- Children taking a psychostimulant for ADD/ADHD and not on a stable dose for at least 2 weeks at time of study enrollment.
- MRI
- Standard MRI exclusion criteria, e.g. orthodontic braces, cochlear implant or other metallic implants which obscure or interfere with the MRI.
- Special Education: Children with a special education placement based on ability or behavior.
- Informed Consent: Inability or unwillingness of child or legal guardian/representative to give written informed consent.
- Child not fluent in English.
- Clinical Contraindications
- Children with a diagnosis of a chronic neurological disorder.
- Children with diagnoses of pervasive developmental disorders (e.g., autism/autism spectrum disorders).
- Children with progressive neurological disease (e.g., degenerative, progressive neoplasm).
- Children with major medical disease (e.g., IDDM, cancer, renal failure).
- Children with a history of neonatal seizures.
- Pregnancy: Children who are pregnant will not be eligible for enrollment.
- Prior Therapy
- Children previously or currently treated with an AED for any reason (other than non chronic benzodiazepine, e.g., ED treatment).
- Children taking any psychoactive agent other than psychostimulants for ADD/ADHD.
- Children taking a psychostimulant for ADD/ADHD and not on a stable dose for at least 2 weeks at time of study enrollment.
- MRI and MRI/EEG Abnormality
- Standard MRI exclusion criteria, e.g. orthodontic braces, cochlear implant or other metallic implants which obscure or interfere with the MRI.
- Special Education: Children with a special education placement based on ability or behavior.
- Informed Consent: Inability or unwillingness of child or legal guardian/representative to give written informed consent.
- Child not fluent in English.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
About this study
This project examines how seizures, and abnormal brain activity, affect language skill in children with Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS). BECTS is a common type of childhood epilepsy, and while BECTS patients stop having seizures by their late teenage years, many studies have shown that these children have language problems that may lead to academic and social difficulties. Using standardized language testing, monitoring of brain activity, and MRI brain imaging, this project aims to determine what particular combination of BECTS symptoms put children most at risk for language problems and whether treatment with anti-epileptic medications may be helpful.
Read the detailed description
Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS), an extremely common type of childhood epilepsy, is traditionally assumed to have a benign course, but recent studies have shown that cognitive function, especially language, is often impaired in BECTS patients. However, it is not clear whether ithe seizures, the centrotemporal spikes (CTS), or other factors cause the negative cognitive consequences that may impact school performance and social interaction. BECTS patients have scattered seizures but very frequent CTS, and may be suffering with undiagnosed cognitive and language deficits. This suggests a causal role for CTS that has not yet been investigated in detail. This project will examine the impact of seizures and CTS on neurocognitive function in BECTS patients, at diagnosis and after one year. We will gather critical information regarding the effect of the anti-epileptic medication levetiracetam on CTS, which will inform a future Phase III clinical trial aimed at eliminating CTS and improving long term outcome.
This study will explore the interactions between CTS, seizures and neuropsychological outcomes using Functional MRI of language in order to decipher changes in neural circuitry that underlie language deficits found in children with BECTS. Using standardized neuropsychological testing and fMRI at the time of diagnosis, this study will first characterize the nature and incidence of language problems in children with BECTS, separating the effects of CTS and seizures. It is expected that children with BECTS will perform below normative standards on tests of language skill, accompanied by aberrations in the neural circuitry supporting language processing as tested with fMRI. These data will also make it possible to characterize which children with BECTS are most at risk for language problems, by taking into account contributing factors such as number of seizures, age of onset, and frequency and lateralization of CTS.
The proposed exploratory clinical trial will also provide key information needed to properly design and conduct a future double blind Phase III randomized clinical trial (RCT) children aimed at improving language outcome through elimination of CTS. Using an open-label dose-ranging design and 1-year follow up, we will determine the best dose of levetiracetam to control seizures, eliminate CTS and be well tolerated. We will also examine the extent of changes in language function and neural circuitry of language with 1-year follow-up neuropsychological testing and fMRI in LEV-treated and untreated BECTS compared to controls (which will document the natural history of neuropsychological function in untreated BECTS children and give additional information about the effect of LEV). The current study will provide crucial information for a future double blind RCT that will the compare the selected dose of levetiracetam to carbamazepine (the current standard of care) in BECTS. This would change clinical practice by demonstrating the need for AED treatment in BECTS to eliminate CTS, in turn improving long term language and cognitive outcome.
- Being tested
- Levetiracetam
- Keywords
- Benign Childhood Epilepsy With Centrotemporal Spikes, Benign Rolandic Epilepsy
- Medical subject headings
- Epilepsy, Rolandic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevetiracetamDrug
Also called Keppra
Medication doses are defined on a mg/kg basis. Dosage form, frequency and titration schedule is based on accepted clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | No intervention | Healthy Control |
| BECTS, no medication | No intervention | BECTS, no medication |
| Levetiracetam Higher dose | Experimental | Levetiracetam Higher dose Receives: Drug: Levetiracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Centrotemporal Spikes per minute on EEG
Measured: 52 weeks
Secondary outcomes (2)
Composite Score on CELF-4 Core Subtests (Language)
Measured: 52 Weeks
fMRI Lateralization indices for three language tasks
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Benign Childhood Epilepsy With Centro-Temporal SpikesStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer Vannest, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01521130
- Sponsor's protocol ID
- R01NS065840-01
- Other IDs
- R01NS065840-01
- Acronym
- FIRST
- Status last verified
- Nov 2017
- First submitted
- 26 Jan 2012
- Last updated
- 14 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tenney JR, Glauser T, Altaye M, Szaflarski JP, Spencer C, Morita D, Vannest J. Longitudinal stability of interictal spikes in benign epilepsy with centrotemporal spikes. Epilepsia. 2016 May;57(5):805-11. doi: 10.1111/epi.13367. Epub 2016 Mar 25.
PubMed 27012680Vannest J, Tenney JR, Altaye M, Byars AW, Spencer C, Maloney TC, Szaflarski JP, Morita D, Glauser TA. Impact of frequency and lateralization of interictal discharges on neuropsychological and fine motor status in children with benign epilepsy with centrotemporal spikes. Epilepsia. 2016 Aug;57(8):e161-7. doi: 10.1111/epi.13445. Epub 2016 Jun 28.
PubMed 27350662
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Effect of Centrotemporal Spikes and Seizures on Language in Children
- ClinicalTrials.gov ID
- NCT01521130
- Acronym / sponsor ID
- FIRST / R01NS065840-01
- Keywords
- Benign Childhood Epilepsy With Centrotemporal Spikes, Benign Rolandic Epilepsy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2012
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 30 Jan 2012 (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.
This project examines how seizures, and abnormal brain activity, affect language skill in children with Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS). BECTS is a common type of childhood epilepsy, and while BECTS patients stop having seizures by their late teenage years, many studies have shown that these children have language problems that may lead to academic and social difficulties. Using standardized language testing, monitoring of brain activity, and MRI brain imaging, this project aims to determine what particular combination of BECTS symptoms put children most at risk for language problems and whether treatment with anti-epileptic medications may be helpful.
Detailed description
Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS), an extremely common type of childhood epilepsy, is traditionally assumed to have a benign course, but recent studies have shown that cognitive function, especially language, is often impaired in BECTS patients. However, it is not clear whether ithe seizures, the centrotemporal spikes (CTS), or other factors cause the negative cognitive consequences that may impact school performance and social interaction. BECTS patients have scattered seizures but very frequent CTS, and may be suffering with undiagnosed cognitive and language deficits. This suggests a causal role for CTS that has not yet been investigated in detail. This project will examine the impact of seizures and CTS on neurocognitive function in BECTS patients, at diagnosis and after one year. We will gather critical information regarding the effect of the anti-epileptic medication levetiracetam on CTS, which will inform a future Phase III clinical trial aimed at eliminating CTS and improving long term outcome.
This study will explore the interactions between CTS, seizures and neuropsychological outcomes using Functional MRI of language in order to decipher changes in neural circuitry that underlie language deficits found in children with BECTS. Using standardized neuropsychological testing and fMRI at the time of diagnosis, this study will first characterize the nature and incidence of language problems in children with BECTS, separating the effects of CTS and seizures. It is expected that children with BECTS will perform below normative standards on tests of language skill, accompanied by aberrations in the neural circuitry supporting language processing as tested with fMRI. These data will also make it possible to characterize which children with BECTS are most at risk for language problems, by taking into account contributing factors such as number of seizures, age of onset, and frequency and lateralization of CTS.
The proposed exploratory clinical trial will also provide key information needed to properly design and conduct a future double blind Phase III randomized clinical trial (RCT) children aimed at improving language outcome through elimination of CTS. Using an open-label dose-ranging design and 1-year follow up, we will determine the best dose of levetiracetam to control seizures, eliminate CTS and be well tolerated. We will also examine the extent of changes in language function and neural circuitry of language with 1-year follow-up neuropsychological testing and fMRI in LEV-treated and untreated BECTS compared to controls (which will document the natural history of neuropsychological function in untreated BECTS children and give additional information about the effect of LEV). The current study will provide crucial information for a future double blind RCT that will the compare the selected dose of levetiracetam to carbamazepine (the current standard of care) in BECTS. This would change clinical practice by demonstrating the need for AED treatment in BECTS to eliminate CTS, in turn improving long term language and cognitive outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | No intervention | –Healthy Control |
| BECTS, no medication | No intervention | –BECTS, no medication |
| Levetiracetam Higher dose | Experimental | Drug: LevetiracetamLevetiracetam Higher dose |
Who may qualify
- Ages
- 5 to 13 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (23 listed)
- Diagnosis: Child has newly diagnosed BECTS according to International League Against Epilepsy (ILAE) criteria (including normal EEG background for age, at least 1 partial onset seizure, and unilateral or bilateral central/mid-temporal sharp waves with a positive horizontal dipole).
- Age: The child's age is between 5 years, 0 months and 13 years, 11 months at study entry.
- Language: The child must be a monolingual native speaker of English.
- Handedness : The child must be right-handed.
- Females: females of child bearing potential must agree to an acceptable and non-systemic form of birth control (including abstinence).
Key exclusion criteria (35 listed)
- Clinical Contraindications
- Children with diagnosis of Benign Occipital Epilepsy (BOE - normal EEG background, and unilateral or bilateral occipital sharp waves activated by eye closure).
- Children with history of primary generalized seizures (absence, myoclonic, drop).
- Children with mixed seizure disorder (e.g., Lennox-Gastaut Syndrome).
- Children sensory seizures only (i.e., auras).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevetiracetamAlso: KeppraMedication doses are defined on a mg/kg basis. Dosage form, frequency and titration schedule is based on accepted clinical practice. | Drug | Levetiracetam Higher dose |
Primary outcome
Number of Centrotemporal Spikes per minute on EEG
Time frame: 52 weeks
2 secondary outcomes
Composite Score on CELF-4 Core Subtests (Language)
Time frame: 52 Weeks
fMRI Lateralization indices for three language tasks
Time frame: 52 Weeks
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 14 Nov 2017.
- Results publication: PubMed 27012680Tenney JR, Glauser T, Altaye M, Szaflarski JP, Spencer C, Morita D, Vannest J. Longitudinal stability of interictal spikes in benign epilepsy with centrotemporal spikes. Epilepsia. 2016 May;57(5):805-11. doi: 10.1111/epi.13367. Epub 2016 Mar 25.
- Results publication: PubMed 27350662Vannest J, Tenney JR, Altaye M, Byars AW, Spencer C, Maloney TC, Szaflarski JP, Morita D, Glauser TA. Impact of frequency and lateralization of interictal discharges on neuropsychological and fine motor status in children with benign epilepsy with centrotemporal spikes. Epilepsia. 2016 Aug;57(8):e161-7. doi: 10.1111/epi.13445. Epub 2016 Jun 28.
Related trials for Benign Childhood Epilepsy With Centro-Temporal Spikes
Recruiting
Sleep Related Memory Consolidation in Children With Age Related Focal Epilepsy.
Benign Epilepsy With Centro Temporal Spikes (BECTS), Atypical Benign Partial Epilepsy (ABPE)
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.
Jennifer Vannest, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Levetiracetam in people with Benign Childhood Epilepsy With Centro-Temporal Spikes, run by Children's Hospital Medical Center, Cincinnati at 1 site 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 23 inclusion and 35 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 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Number of Centrotemporal Spikes per minute on EEG (time frame: 52 weeks). 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 NCT01521130, which also lists 2 linked publications.
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 14 Nov 2017.