Clinical trial NCT04219930: Nucleotide Protein -3 in Epileptic Children
Official title: Biochemical Role of Nucleotide Protein -3 That Activate the Interleukin-1B in Epileptic Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Epilepsy in Children
Keywords: Epilepsy
Children
NLRP3
Interleukin B1
Nuclear Factor-Kappa B
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Epileptic children

Brief summary: Epilepsy is one of common serious neurological malfunction, characterized by recurrent unprovoked seizures. It always accompanied with multitude of complications as cognitive, behavioral, and psychiatric disorders.

Experimental studies and clinical evidence obtained in animal models of epilepsy and human brain specimen from various drug-resistant forms of epilepsy show the activation of the innate and adaptive immunity mechanisms and the induction of the associated inflammatory processes in the epileptogenic foci.

Detailed description: Epilepsy affects approximately 1% of the world population. Lifetime prevalence of childhood and adolescence epilepsy (children \<18 years) in Upper Egypt was 9.7/1000, with higher prevalence among children \<12 years (10.8/1000).

There is a clear cause for epilepsy in only a minority of the cases, while in up to70% of all case of epilepsy in adults and children, no cause can be discovered. Some of the main causes of epilepsy include: Low oxygen during birth, head injuries that occur during birth or from accidents during youth or adulthood, brain tumors, infections such as meningitis or encephalitis, stroke or any other type of damage to the brain.

A role of inflammatory molecules in the generation of seizures had been first investigated when selected anti-inflammatory treatments, in particular, steroids, immuno-globulins, and adrenocorticotropic hormone (ACTH), were shown to control seizures in pediatric epilepsies refractory to conventional anticonvulsive drugs. In addition, specific epileptic disorders have been associated with the presence of neuronal antigen-directed antibodies in plasma or cerebrospinal fluid (CSF).

A nucleotide-binding oligomerization domains (NODs) are cytosolic proteins that include key regulators of apoptosis and pathogen resistance in mammals and plants. A large number of NODs contain leucine-rich repeats (LRRs), hence referred to as NOD-LRR proteins. The NLRP3 gene provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. NLR family have two common features: the first is a nucleotide-binding oligomerization domain which is bound by ribonucleotide-phosphates (rNTP) and is important for self-oligomerization. The second is a C-terminal leucine-rich repeat, which serves as a ligand-recognition domain for other receptors (e.g. Toll like receptor (TLR)) or microbial ligands, while NLRP3 has been identified in microglial cells.

Eligibility criteria: Inclusion Criteria:

* Epileptic children in Assiut university hospital, pediatric department, neurology unit.

Exclusion Criteria:

* Children with other chronic disease such as liver, kidney or heart disease
* patient who have apparent infection

Primary outcomes:
measure: The mean difference of nucleotide protein -3 inflammatory marker expression in epileptic children and controls
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: He Q, Jiang L, Man S, Wu L, Hu Y, Chen W. Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model. Curr Neurovasc Res. 2018;15(3):186-192. doi: 10.2174/1567202615666180731100224.
citation: Farghaly WM, Abd Elhamed MA, Hassan EM, Soliman WT, Yhia MA, Hamdy NA. Prevalence of childhood and adolescence epilepsy in Upper Egypt (desert areas). Egypt J Neurol Psychiatr Neurosurg. 2018;54(1):34. doi: 10.1186/s41983-018-0032-0. Epub 2018 Nov 9.
citation: Xu D, Miller SD, Koh S. Immune mechanisms in epileptogenesis. Front Cell Neurosci. 2013 Nov 8;7:195. doi: 10.3389/fncel.2013.00195. eCollection 2013.