Exploration of Genotype Based Personalized Prescription of Valproate Sodium in Anti-epileptic Treatment

Study Overview
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Brief Summary
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The purpose of this study is to investigate the relationship between the side effects of valproate sodium in the treatment of epilepsy in Han Chinese and the genetic polymorphisms of drug metabolizing enzymes and pharmacokinetics of valproate sodium.

Detailed Description
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Valproate sodium is a widely applied agent in the treatment of epilepsy. Although Valproate sodium is effective in clinic, it is able to induce several side effects, including weight gain, thinned hair, loss of appetite, nausea, vomiting, hepatotoxicity, hematotoxicity, thrill, etc. However, the remarkable variability of the reactions to the drug -- the incidence of side effect or the outcome of the treatment -- has been observed among patients. Valproate sodium is metabolized by some enzymes in the liver to transform it into several unreactive chemicals for excretion. Among them there are two toxic metabolites catalyzed by the specific metabolic enzymes. This study is designed to explore the genetic variation among individuals in the key processes of the deactivation and elimination of Valproate sodium in order to find out whether these genetic factors are associated to the side effects or efficacy. The further understanding into the factors concerning on the drug might imply possible solution to minimize the incidence of side effects in epileptic patients.

Official Title
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Exploration of Genotype Based Personalized Prescription of Valproate Sodium in Anti-epileptic Treatment

Conditions
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Epilepsy, Adverse Effects

Intervention / Treatment
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* Drug: valproate sodium
* Genetic: Polymorphism Analysis
* Other: Pharmacokinetic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients must have been diagnosed as epilepsy according to The International League Against Epilepsy (ILAE) criteria published in 2001. The patients must sign the informed consent. And for the patients who are under 18 years old, both the signatures of their legal guardians and that of the patients are required on the written informed consent. The patients are receiving the regimen of 15-30mg/kg valproate sodium given as daily oral administration. Exclusion Criteria: Pregnant women, women in breast-feeding period and the women who refuse to take contraception measures during treatment. Patients with poor compliance. Patients who have blood transfusion during the therapy.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| epileptic patients<br>epileptic patients receiving treatment with continuous Sodium Valproate | Drug: valproate sodium<br>* oral administration,15-30mg/kg,daily<br>* Other names: Depakine;Genetic: Polymorphism Analysis<br>* Analysis of genetic polymorphisms of the drug metabolic enzymes involving in the deactivation and elimination of Valproate sodium<br>Other: Pharmacokinetic analysis<br>* laboratory analysis of concentration of Valproate sodium and 4-ene-Valproate in plasma<br>* Other names: concentration detection method;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| epileptic seizure |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, valproate sodium, metabolic enzymes, adverse effects, systemic adverse effects