Relationship Between Polymorphisms of TRPV1 and KCC2 Gene in Children With Febrile Seizures
NCT ID: NCT04368936
Last Updated: 2021-10-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
121 participants
OBSERVATIONAL
2015-03-31
2021-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
FS, as defined by the American Academy of Pediatrics (AAP), are " seizure occurring in febrile children between the ages of 6 and 60 months who do not have an intracranial infection, metabolic disturbance, or history of afebrile seizures ".
Simple febrile seizure is defined as a short (\<15 min) generalized seizure, not repeat within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. Complex febrile seizures are a focal, or generalized and prolonged seizure, of a duration of greater than 15 min, recurring more than once in 24 h, and/or associated with postictal neurologic abnormalities, more frequently a postictal palsy (Todd's palsy), or with previous neurologic deficits.
The etiology of FN is still the subject of numerous studies and it is known that it can depend on genetic predisposition.
Animal studies have shown that mice without the KCC2 gene have frequent generalized seizures, while those with heterozygous deletion of the KCC2 gene have a reduced threshold for seizure onset. In the human population, mutations of this gene have been reported in children with FN as well as in children with epilepsy. There is no examined an association between polymorphism rs2297201 KCC2 gene and FS.
Studies have shown an association between TRPV1 genes and the appearance of FS in experimental models, however, similar studies in the human population have not been done so far. Studies Moria et al. 2012 showed that polymorphism rs222797 TRPV1 gene involve the regulation of human cortical excitability, glutamate transmission and increased neuronal excitability. The C allele this polymorphism is associated with a greater maximal response to the caspaicin and anadamine agonists. All of this indicate that changes TRPV1 gene that lead to increased channel function may suggest a predisposition for FS.
Since FS are genetically controlled, we want to determine the association of TRPV1 and KCC2 gene polymorphisms with the occurrence of FN.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_CONTROL
CROSS_SECTIONAL
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
FS: Febrile Seizures
Involved patient with diagnosed Febrile Seizures which were hospitalized or recieved ambulatory treatment in University Children´s Hospital in Belgrade. Ages 1-14 years
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
CN: Control group
The control group was made of healthy children older than 5 years of age, which have never had any neurological disorders in their anamnesis and who were patients in preschool or school dispensaries in the city of Belgrade
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
SFS : group of individuals with simple FS
Simplex febrile seizures (SFS) last shorter than 15 minutes and their type is tonic-clonic. Also, they did not show signs of recidivism during the first 24 hours and were diagnosed at the patients aged from 6th months to 5th year
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
CFS : group of individuals with complex FS
Complex febrile seizures (CFS) were diagnosed at those patients that had focal seizure or epileptic status or seizure having the body temperature lower than 38 degree, which occurred outside of the typical age group and finally which repeated in the first 24 hours again
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
WFS: group of individuals with FS and without epilepsia
group of children with Febrile Seizure and not developed Epilepsia
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
EFS: group of individuals with Epilepsia and Febrile Seizures
Group of children with Febrile Seizures, who have developed Epilepsy
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Isolated DNA, Real Time PCR
We are isolated DNA from the blood sample. To determine the genotypes of the analyzed polymorphisms use real-time PCR using TaqMan essays.
When analyzing the KCC2 polymorphisms, the VIC dye gene corresponded to the C allele, and the FAM dye corresponded to the T allele, while at the TRPV1 gene polymorphism, the VIC dye corresponded to the C allele and the FAM dye to the G allele.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* For each patient, a diagnosis of FS was made based on the ILAE definition (International Leage
* The main criterion for inclusion in the study was enhanced FS without prior occurrence of afebrile seizure.
Exclusion Criteria
* Patients with incomplited medical documentation
1 Year
14 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Institut za Rehabilitaciju Sokobanjska Beograd
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Tamara Filipovic
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Sanja Dimitrijevic, PhD
Role: PRINCIPAL_INVESTIGATOR
Specila hospital for cerebral palsy and developmental neurology
References
Explore related publications, articles, or registry entries linked to this study.
Leung AK, Hon KL, Leung TN. Febrile seizures: an overview. Drugs Context. 2018 Jul 16;7:212536. doi: 10.7573/dic.212536. eCollection 2018.
Dimitrijevic S, Cvjeticanin S, Pusica A, Jekic B, Filipovic T, Nikolic D. Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study. Biomed Res Int. 2018 Jul 5;2018:7845904. doi: 10.1155/2018/7845904. eCollection 2018.
Reid AY, Riazi K, Campbell Teskey G, Pittman QJ. Increased excitability and molecular changes in adult rats after a febrile seizure. Epilepsia. 2013 Apr;54(4):e45-8. doi: 10.1111/epi.12061. Epub 2013 Jan 7.
Puskarjov M, Seja P, Heron SE, Williams TC, Ahmad F, Iona X, Oliver KL, Grinton BE, Vutskits L, Scheffer IE, Petrou S, Blaesse P, Dibbens LM, Berkovic SF, Kaila K. A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. EMBO Rep. 2014 Jun;15(6):723-9. doi: 10.1002/embr.201438749. Epub 2014 Mar 24.
Huang WX, Yu F, Sanchez RM, Liu YQ, Min JW, Hu JJ, Bsoul NB, Han S, Yin J, Liu WH, He XH, Peng BW. TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain. Brain Behav Immun. 2015 Aug;48:68-77. doi: 10.1016/j.bbi.2015.01.017. Epub 2015 Mar 20.
Xu H, Tian W, Fu Y, Oyama TT, Anderson S, Cohen DM. Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene. Am J Physiol Renal Physiol. 2007 Dec;293(6):F1865-76. doi: 10.1152/ajprenal.00347.2007. Epub 2007 Oct 3.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
SBCPRN2
Identifier Type: -
Identifier Source: org_study_id