SeizuresNCT03934268
A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy
An observational study of Seizures and Seizure Disorder, run by Children's Hospital of Fudan University at 1 site in China.
Trial summary
The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. Read more about this study
- Who is it for?
- Ages 0 to 28 days
- Conditions the study is for
- Seizures, Seizure Disorder, Seizure Newborn
- What is being tested?
- KCNQ2
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2017to Dec 2023
- 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 0 to 28 days
- All sexes
- No healthy volunteers
- Child
Study population: The subjects came from sub-central hospitals and the newborns were hospitalized in the neonatal department for primary seizure.
Who may be able to join
- Primary or initial convulsion
- Postnatal age <28 days.
- Seizure in the neonatal period
- Informed consent of parents
Who cannot join
- Seizure caused by congenital cerebral hypoplasia or multiple structural malformations.
- Seizure caused by other system-related syndromes.
- Seizure caused by perinatal or postpartum factors such as HIE, infection, intracranial hemorrhage, etc.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Children Hospital of Fudan University
Shanghai, Shanghai Municipality, 201102
Wenhao Zhou, Doctor, (+86)021-64931003, zwhchfu@126.com
About this study
The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.
Read the detailed description
Convulsion is the most common clinical manifestation of neonatal central nervous system dysfunction. the incidence of convulsion is very high in neonatal period, especially in the first week after birth. the incidence of convulsion decreases gradually with the increase of age. The incidence of convulsion reported by Bassan et al was 1.5 ‰ ~ 3.5 ‰ in term infants and 10% ≤ 130% in premature infants. Most of the neonatal convulsions suggest that there are serious primary diseases in the body. in addition to hypoxic-ischemic encephalopathy, intracranial hemorrhage and infection, a large number of studies have proved that genetic factors play a key role in the occurrence of neonatal convulsions and epileptic encephalopathy in infants. Nearly 20% to 50% of neonatal convulsions are idiopathic convulsions. it has been thought that KCNQ2 gene, a potassium channel subunit located in 20q11.3, and KCNQ3 gene, another potassium channel subunit located in 8q24, are mutated. Is the molecular basis for some benign familial neonatal convulsions, Usually the prognosis is good, but with the expansion of the study sample, investigators found that KCNQ2 may be associated with refractory epileptic encephalopathy, and there are few international reports in this regard. The study of KCNQ2 gene has led to a new understanding of the etiology of neonatal convulsion. The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.
- Conditions
- Seizures, Seizure Disorder, Seizure Newborn, Seizures, Generalized, Epileptic Encephalopathy, Epileptic Encephalopathy, Neonatal-onset
- Being tested
- KCNQ2
- Medical subject headings
- Seizures, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KCNQ2Genetic
The researchers extracted DNA from the baby's serum and sent it to WES to get the baby's total exon sequence.
| Study group | Role | What they receive |
|---|---|---|
| infants with seizure with KCNQ2 gene mutation. | Infants who met the inclusion criteria were enrolled in this study. The infants will get their own DNA sequencing results by WES technology. The researchers found that some of them carried mutations in the KCNQ2 gene. so they wanted to compare whether there were differences with or without KCNQ2 gene mutations in the efficacy of anticonvulsants or long-term neurodevelopment in different exposure groups. Receives: Genetic: KCNQ2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of seizure in children with KCNQ2 within 28 days of age
The investigators used WES to screen for neonatal onset seizure and calculated the incidence of KCNQ2 gene mutations in these neonates.
Measured: From birth to under 28 days of age
Secondary outcomes (3)
Recurrence rate of KNCQ2 gene-related convulsion in children under 1 year of age
Some neonates with seizure associated with KCNQ2 gene mutation will develop epileptic encephalopathy or syndrome at a later stage.
The researchers calculated the probability of recurrent seizures or progression in neonates with seizure associated with KCNQ2 gene mutations within the age of one year.
Measured: From birth to under 1 year of age
Efficacy of first-line anticonvulsants in children with KCNQ2 gene-related convulsions
Some non-benign KCNQ2 gene-related convulsions require anticonvulsant intervention, and investigators hope to observe and obtain the effective rate of first-line anticonvulsant intervention. To determine whether the convulsion stopped or the frequency of convulsion decreased within 72 hours after taking the drug. If convulsions stop or the frequency of seizures decreases, drug intervention is considered effective.
Measured: From the beginning of drug intervention to 72 hours after taking the drug.
Proportion of infants classified as having "developmental delay" (MDI <70 on BSID-III or either Language or Cognitive Score <70 on the Bayley-III)
The investigators plan to use the bayley Neurodevelopmental scale to assess the neurodevelopmental status of infants with KCNQ2 gene-associated epileptic encephalopathy within 2 years of age.
Measured: The infants will be evaluated by bayley Neurodevelopment scale at the age of about two years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start1 Jan 2017
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for SeizuresStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wenhao Zhou, Prof., Study chair, Children Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03934268
- Sponsor's protocol ID
- CHFudanU_NNICU12
- Status last verified
- Sep 2023
- First submitted
- 29 Apr 2019
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kuersten M, Tacke M, Gerstl L, Hoelz H, Stulpnagel CV, Borggraefe I. Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review. Eur J Med Genet. 2020 Jan;63(1):103628. doi: 10.1016/j.ejmg.2019.02.001. Epub 2019 Feb 14.
PubMed 30771507Cornet MC, Sands TT, Cilio MR. Neonatal epilepsies: Clinical management. Semin Fetal Neonatal Med. 2018 Jun;23(3):204-212. doi: 10.1016/j.siny.2018.01.004. Epub 2018 Jan 31.
PubMed 29426806Reif PS, Tsai MH, Helbig I, Rosenow F, Klein KM. Precision medicine in genetic epilepsies: break of dawn? Expert Rev Neurother. 2017 Apr;17(4):381-392. doi: 10.1080/14737175.2017.1253476. Epub 2016 Nov 10.
PubMed 27781560Hani AJ, Mikati HM, Mikati MA. Genetics of pediatric epilepsy. Pediatr Clin North Am. 2015 Jun;62(3):703-22. doi: 10.1016/j.pcl.2015.03.013.
PubMed 26022171Manville RW, Abbott GW. Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket. Nat Commun. 2018 Sep 21;9(1):3845. doi: 10.1038/s41467-018-06339-2.
PubMed 30242262Manville RW, Papanikolaou M, Abbott GW. Direct neurotransmitter activation of voltage-gated potassium channels. Nat Commun. 2018 May 10;9(1):1847. doi: 10.1038/s41467-018-04266-w.
PubMed 29748663
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy
- ClinicalTrials.gov ID
- NCT03934268
- Acronym / sponsor ID
- CHFudanU_NNICU12
- Conditions
- Seizures, Seizure Disorder, Seizure Newborn, Seizures, Generalized, Epileptic Encephalopathy, Epileptic Encephalopathy, Neonatal-onset
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 1 May 2019 (actual)
- 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.
The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.
Detailed description
Convulsion is the most common clinical manifestation of neonatal central nervous system dysfunction. the incidence of convulsion is very high in neonatal period, especially in the first week after birth. the incidence of convulsion decreases gradually with the increase of age. The incidence of convulsion reported by Bassan et al was 1.5 ‰ ~ 3.5 ‰ in term infants and 10% ≤ 130% in premature infants. Most of the neonatal convulsions suggest that there are serious primary diseases in the body. in addition to hypoxic-ischemic encephalopathy, intracranial hemorrhage and infection, a large number of studies have proved that genetic factors play a key role in the occurrence of neonatal convulsions and epileptic encephalopathy in infants. Nearly 20% to 50% of neonatal convulsions are idiopathic convulsions. it has been thought that KCNQ2 gene, a potassium channel subunit located in 20q11.3, and KCNQ3 gene, another potassium channel subunit located in 8q24, are mutated. Is the molecular basis for some benign familial neonatal convulsions, Usually the prognosis is good, but with the expansion of the study sample, investigators found that KCNQ2 may be associated with refractory epileptic encephalopathy, and there are few international reports in this regard. The study of KCNQ2 gene has led to a new understanding of the etiology of neonatal convulsion. The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| infants with seizure with KCNQ2 gene mutation. | – | Genetic: KCNQ2Infants who met the inclusion criteria were enrolled in this study. The infants will get their own DNA sequencing results by WES technology. The researchers found that some of them carried mutations in the KCNQ2 gene. so they wanted to compare whether there were differences with or without KCNQ2 gene mutations in the efficacy of anticonvulsants or long-term neurodevelopment in different exposure groups. |
Who may qualify
- Ages
- 0 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The subjects came from sub-central hospitals and the newborns were hospitalized in the neonatal department for primary seizure.
Key inclusion criteria (4 listed)
- Primary or initial convulsion
- Postnatal age <28 days.
- Seizure in the neonatal period
- Informed consent of parents
Key exclusion criteria (3 listed)
- Seizure caused by congenital cerebral hypoplasia or multiple structural malformations.
- Seizure caused by other system-related syndromes.
- Seizure caused by perinatal or postpartum factors such as HIE, infection, intracranial hemorrhage, etc.
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 |
|---|---|---|
| KCNQ2The researchers extracted DNA from the baby's serum and sent it to WES to get the baby's total exon sequence. | Genetic | infants with seizure with KCNQ2 gene mutation. |
Primary outcome
Incidence of seizure in children with KCNQ2 within 28 days of age
Time frame: From birth to under 28 days of age
The investigators used WES to screen for neonatal onset seizure and calculated the incidence of KCNQ2 gene mutations in these neonates.
3 secondary outcomes
Recurrence rate of KNCQ2 gene-related convulsion in children under 1 year of age
Time frame: From birth to under 1 year of age
Efficacy of first-line anticonvulsants in children with KCNQ2 gene-related convulsions
Time frame: From the beginning of drug intervention to 72 hours after taking the drug.
Proportion of infants classified as having "developmental delay" (MDI <70 on BSID-III or either Language or Cognitive Score <70 on the Bayley-III)
Time frame: The infants will be evaluated by bayley Neurodevelopment scale at the age of about two years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Background: PubMed 30771507Kuersten M, Tacke M, Gerstl L, Hoelz H, Stulpnagel CV, Borggraefe I. Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review. Eur J Med Genet. 2020 Jan;63(1):103628. doi: 10.1016/j.ejmg.2019.02.001. Epub 2019 Feb 14.
- Background: PubMed 29426806Cornet MC, Sands TT, Cilio MR. Neonatal epilepsies: Clinical management. Semin Fetal Neonatal Med. 2018 Jun;23(3):204-212. doi: 10.1016/j.siny.2018.01.004. Epub 2018 Jan 31.
- Background: PubMed 27781560Reif PS, Tsai MH, Helbig I, Rosenow F, Klein KM. Precision medicine in genetic epilepsies: break of dawn? Expert Rev Neurother. 2017 Apr;17(4):381-392. doi: 10.1080/14737175.2017.1253476. Epub 2016 Nov 10.
- Background: PubMed 26022171Hani AJ, Mikati HM, Mikati MA. Genetics of pediatric epilepsy. Pediatr Clin North Am. 2015 Jun;62(3):703-22. doi: 10.1016/j.pcl.2015.03.013.
- Results publication: PubMed 30242262Manville RW, Abbott GW. Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket. Nat Commun. 2018 Sep 21;9(1):3845. doi: 10.1038/s41467-018-06339-2.
- Results publication: PubMed 29748663Manville RW, Papanikolaou M, Abbott GW. Direct neurotransmitter activation of voltage-gated potassium channels. Nat Commun. 2018 May 10;9(1):1847. doi: 10.1038/s41467-018-04266-w.
- Individual participant dataSharing planned: No
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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.
Wenhao Zhou, Prof. study chair
Children Hospital of Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Seizures and Seizure Disorder, run by Children's Hospital of Fudan University at 1 site in China.
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: status not confirmed, as of the sponsor's last update on 21 Sep 2023. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wenhao Zhou, Prof. ((+86) 021-64931168, zwhchfu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of seizure in children with KCNQ2 within 28 days of age (time frame: From birth to under 28 days of age). 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 NCT03934268, which also lists 6 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 21 Sep 2023.