<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03822741</url>
  </required_header>
  <id_info>
    <org_study_id>CHFudanU_NNICU10</org_study_id>
    <nct_id>NCT03822741</nct_id>
  </id_info>
  <brief_title>Etiology and Treatment of Neonatal Seizure</brief_title>
  <official_title>Gene Profiling and Individualized Treatment of Neonatal Seizure in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital of Fudan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Genetic diagnosis for neonates suffering from epilepsy has important implications for&#xD;
      treatment, prognosis, and development of precision medicine strategies. Investigator&#xD;
      performed exome sequencing (ES) or targeted sequencing on neonates with seizure onset within&#xD;
      the first month of life. Investigator subgrouped our patients based on the onset age of&#xD;
      seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic&#xD;
      features and treatment strategies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Seizure is one of the most common neurological conditions in neonates, and has substantial&#xD;
      impact on patients'quality of life and social integration. Epileptic encephalopathy is&#xD;
      characterized by refractory seizures, cognitive dysfunction, and poor prognosis. Despite the&#xD;
      recent progress in technology, molecular diagnosis of neonates suffering from possible&#xD;
      epileptic seizures can be challenging, due to genetic and phenotypic heterogeneities. A large&#xD;
      number of specific pathogenic variations have been related to various forms of epilepsies.&#xD;
      Next-generation sequencing (NGS) has significantly improved the molecular diagnosis for rare&#xD;
      diseases. NGS focusing on genes known to be associated with human diseases is a practical&#xD;
      approach as a first-tier assessment for patients with heterogeneous genetic background. In&#xD;
      addition, currently medical therapy for seizure is not based on the etiology, but the&#xD;
      clinical manifestations, and the main purpose is not to rescue the underlying diseases&#xD;
      process, but just to reduce the likelihood of seizures occurrence. In this study,&#xD;
      Investigator performed NGS on neonates with seizure onset before 1 year of age, to detect and&#xD;
      quantify genetic variants, and assess existing therapeutic effects. Our findings will have&#xD;
      important implications for the development of precision medicine strategies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 8, 2016</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Mutation rate of common seizure genes</measure>
    <time_frame>From the oneset of seizure to the genetic sequencing finish, the process may last up to 3 months.</time_frame>
    <description>We'll get the genetic profiles of all neonates who had seizures during this period. The mutation rate of common variant gene was calculated by gene spectrum.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of seizure free</measure>
    <time_frame>From the onset of seizure to 6 months after the onset of seizure</time_frame>
    <description>After the onset of seizure, through clinical management and individualized intervention, we expect to observe the number and proportion of effective seizure treatments.</description>
  </primary_outcome>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Seizures</condition>
  <condition>Seizure Disorder</condition>
  <condition>Seizure Newborn</condition>
  <condition>Seizure Generalized</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Biological samples contain 2ml of blood, which is used to extract DNA from the blood for gene&#xD;
      sequencing.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The subjects were treated in the Department of Neonatology of Children Hospital of Fudan&#xD;
        University. All samples in this study were collected with appropriate informed consent and&#xD;
        approval of the ethics committee of Children's Hospital, Fudan University. The methods used&#xD;
        in this study were carried out in accordance with the approved guidelines.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  severe seizures in neonates or generalized epilepsy or intractable epilepsy in infancy&#xD;
             with generalized tonic-clonic seizures,&#xD;
&#xD;
          -  seizures onset before 1 year of age,&#xD;
&#xD;
          -  epileptic syndromes/epileptic-encephalopathies with unknown etiology.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients were excluded if they had traumas, central nervous system infections,&#xD;
             hypoxic-ischemic encephalopathy, vascular events, systemic infections, and diagnosed&#xD;
             metabolic disorders, and pathogenic copy-number variants were identified using&#xD;
             array-based comparative genomic hybridization (CGH).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wenhao Zhou, Doctor</last_name>
    <role>Study Chair</role>
    <affiliation>Children's Hospital of Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wenhao Zhou, Doctor</last_name>
    <email>zwhchfu@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lin Yang, Doctor</last_name>
    <email>yanglin_fudan@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children Hospital of Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>201102</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wenhao Zhou, Doctor</last_name>
      <phone>(+86)021-64931003</phone>
      <email>zwhchfu@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015 Dec;14(12):1219-28. doi: 10.1016/S1474-4422(15)00199-4. Epub 2015 Sep 20. Erratum In: Lancet Neurol. 2016 Mar;15(3):241.</citation>
    <PMID>26416172</PMID>
  </reference>
  <reference>
    <citation>Lemke JR, Riesch E, Scheurenbrand T, Schubach M, Wilhelm C, Steiner I, Hansen J, Courage C, Gallati S, Burki S, Strozzi S, Simonetti BG, Grunt S, Steinlin M, Alber M, Wolff M, Klopstock T, Prott EC, Lorenz R, Spaich C, Rona S, Lakshminarasimhan M, Kroll J, Dorn T, Kramer G, Synofzik M, Becker F, Weber YG, Lerche H, Bohm D, Biskup S. Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia. 2012 Aug;53(8):1387-98. doi: 10.1111/j.1528-1167.2012.03516.x. Epub 2012 May 21.</citation>
    <PMID>22612257</PMID>
  </reference>
  <reference>
    <citation>Moller RS, Larsen LH, Johannesen KM, Talvik I, Talvik T, Vaher U, Miranda MJ, Farooq M, Nielsen JE, Svendsen LL, Kjelgaard DB, Linnet KM, Hao Q, Uldall P, Frangu M, Tommerup N, Baig SM, Abdullah U, Born AP, Gellert P, Nikanorova M, Olofsson K, Jepsen B, Marjanovic D, Al-Zehhawi LI, Penalva SJ, Krag-Olsen B, Brusgaard K, Hjalgrim H, Rubboli G, Pal DK, Dahl HA. Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies. Mol Syndromol. 2016 Sep;7(4):210-219. doi: 10.1159/000448369. Epub 2016 Aug 20.</citation>
    <PMID>27781031</PMID>
  </reference>
  <reference>
    <citation>Striano P, Zara F. Epilepsy: Common and rare epilepsies share genetic determinants. Nat Rev Neurol. 2017 Apr;13(4):200-201. doi: 10.1038/nrneurol.2017.30. Epub 2017 Mar 10. No abstract available.</citation>
    <PMID>28281535</PMID>
  </reference>
  <reference>
    <citation>Striano P, Vari MS, Mazzocchetti C, Verrotti A, Zara F. Management of genetic epilepsies: From empirical treatment to precision medicine. Pharmacol Res. 2016 May;107:426-429. doi: 10.1016/j.phrs.2016.04.006. Epub 2016 Apr 11.</citation>
    <PMID>27080588</PMID>
  </reference>
  <reference>
    <citation>Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010 Sep;38(16):e164. doi: 10.1093/nar/gkq603. Epub 2010 Jul 3.</citation>
    <PMID>20601685</PMID>
  </reference>
  <reference>
    <citation>Myers CT, Mefford HC. Advancing epilepsy genetics in the genomic era. Genome Med. 2015 Aug 25;7(1):91. doi: 10.1186/s13073-015-0214-7.</citation>
    <PMID>26302787</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 2, 2018</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>February 21, 2021</last_update_submitted>
  <last_update_submitted_qc>February 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>seizure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03822741
org study id: CHFudanU_NNICU10
nct id: NCT03822741
lead sponsor: 
has dmc: Yes
Genetic diagnosis for neonates suffering from epilepsy has important implications for
      treatment, prognosis, and development of precision medicine strategies. Investigator
      performed exome sequencing (ES) or targeted sequencing on neonates with seizure onset within
      the first month of life. Investigator subgrouped our patients based on the onset age of
      seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic
      features and treatment strategies.
Seizure is one of the most common neurological conditions in neonates, and has substantial
      impact on patients'quality of life and social integration. Epileptic encephalopathy is
      characterized by refractory seizures, cognitive dysfunction, and poor prognosis. Despite the
      recent progress in technology, molecular diagnosis of neonates suffering from possible
      epileptic seizures can be challenging, due to genetic and phenotypic heterogeneities. A large
      number of specific pathogenic variations have been related to various forms of epilepsies.
      Next-generation sequencing (NGS) has significantly improved the molecular diagnosis for rare
      diseases. NGS focusing on genes known to be associated with human diseases is a practical
      approach as a first-tier assessment for patients with heterogeneous genetic background. In
      addition, currently medical therapy for seizure is not based on the etiology, but the
      clinical manifestations, and the main purpose is not to rescue the underlying diseases
      process, but just to reduce the likelihood of seizures occurrence. In this study,
      Investigator performed NGS on neonates with seizure onset before 1 year of age, to detect and
      quantify genetic variants, and assess existing therapeutic effects. Our findings will have
      important implications for the development of precision medicine strategies.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Mutation rate of common seizure genes
time frame: From the oneset of seizure to the genetic sequencing finish, the process may last up to 3 months.
description: We'll get the genetic profiles of all neonates who had seizures during this period. The mutation rate of common variant gene was calculated by gene spectrum.
measure: Rate of seizure free
time frame: From the onset of seizure to 6 months after the onset of seizure
description: After the onset of seizure, through clinical management and individualized intervention, we expect to observe the number and proportion of effective seizure treatments.
Biological samples contain 2ml of blood, which is used to extract DNA from the blood for gene
      sequencing.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Months
healthy volunteers: No
last name: Wenhao Zhou, Doctor
role: Study Chair
affiliation: Children's Hospital of Fudan University
last name: Wenhao Zhou, Doctor
email: zwhchfu@126.com
last name: Lin Yang, Doctor
email: yanglin_fudan@163.com
facility: 
status: Recruiting
contact: 
country: China
citation: EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015 Dec;14(12):1219-28. doi: 10.1016/S1474-4422(15)00199-4. Epub 2015 Sep 20. Erratum In: Lancet Neurol. 2016 Mar;15(3):241.
PMID: 26416172
citation: Lemke JR, Riesch E, Scheurenbrand T, Schubach M, Wilhelm C, Steiner I, Hansen J, Courage C, Gallati S, Burki S, Strozzi S, Simonetti BG, Grunt S, Steinlin M, Alber M, Wolff M, Klopstock T, Prott EC, Lorenz R, Spaich C, Rona S, Lakshminarasimhan M, Kroll J, Dorn T, Kramer G, Synofzik M, Becker F, Weber YG, Lerche H, Bohm D, Biskup S. Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia. 2012 Aug;53(8):1387-98. doi: 10.1111/j.1528-1167.2012.03516.x. Epub 2012 May 21.
PMID: 22612257
citation: Moller RS, Larsen LH, Johannesen KM, Talvik I, Talvik T, Vaher U, Miranda MJ, Farooq M, Nielsen JE, Svendsen LL, Kjelgaard DB, Linnet KM, Hao Q, Uldall P, Frangu M, Tommerup N, Baig SM, Abdullah U, Born AP, Gellert P, Nikanorova M, Olofsson K, Jepsen B, Marjanovic D, Al-Zehhawi LI, Penalva SJ, Krag-Olsen B, Brusgaard K, Hjalgrim H, Rubboli G, Pal DK, Dahl HA. Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies. Mol Syndromol. 2016 Sep;7(4):210-219. doi: 10.1159/000448369. Epub 2016 Aug 20.
PMID: 27781031
citation: Striano P, Zara F. Epilepsy: Common and rare epilepsies share genetic determinants. Nat Rev Neurol. 2017 Apr;13(4):200-201. doi: 10.1038/nrneurol.2017.30. Epub 2017 Mar 10. No abstract available.
PMID: 28281535
citation: Striano P, Vari MS, Mazzocchetti C, Verrotti A, Zara F. Management of genetic epilepsies: From empirical treatment to precision medicine. Pharmacol Res. 2016 May;107:426-429. doi: 10.1016/j.phrs.2016.04.006. Epub 2016 Apr 11.
PMID: 27080588
citation: Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010 Sep;38(16):e164. doi: 10.1093/nar/gkq603. Epub 2010 Jul 3.
PMID: 20601685
citation: Myers CT, Mefford HC. Advancing epilepsy genetics in the genomic era. Genome Med. 2015 Aug 25;7(1):91. doi: 10.1186/s13073-015-0214-7.
PMID: 26302787
responsible party type: Sponsor
mesh term: Seizures
mesh term: Epilepsy