Seizure
Conditions
Keywords
epilepsy, pharmacoresistant, antiepileptic drug, pharmacokinetic, pharmacodynamic, pharmacogenetic
Brief summary
Pharmacoresistant epilepsy remains around 30% despite the development of 25 anti epileptic drugs. Of course, this can be explained by pharmacoresistant epileptic brain diseases, as exemplified by some genetic diseases. However, the lack of specific guidelines for the choice of the anti epileptic drugs (apart from generalized and partial epilepsy) and the very large number of drugs with different and sometimes complex metabolism are challenges for neurologists. Among the 30 % of pharmacoresistant epilepsy, there is a part related to pharmacokinetic drawbacks that could be overcome with a more rigorous approach (i.e. dosage and pharmacogenetics tools). Moreover, the new anti epileptic drugs have metabolism more unrelated with the cytochrome P450 and less generalised adverse events. However, their metabolism could be more complexe (i.e. the less known Uridine 5'-diphospho-glucuronyltransferase (UGT) pathway) and bring more insidious neurological adverse events (i.e. depression, anxiety exacerbation, cognitive disorders worsening) which could largely impede the observance and the quality of life even if the number of seizure is reduced or not. The goal is to determine the predictive and the modulating factors of pharmacoresistance with a global analysis (i.e. whatever the anti epileptic drugs) and with a specific analysis (drug by drug) from a cohort of 1000 patients.
Detailed description
The goal is to determine the predictive and the modulating factors of pharmacoresistance with a global analysis (i.e. whatever the anti epileptic drugs) and with a specific analysis (drug by drug with their specific metabolism pathways) from a cohort of 1000 patients. The response to the antiepileptic drugs modification will be analyse 3 months after the modification, with the analysis of the number of seizures, the quality of life, the Clinical Global Impression, the adverse events, the systematic dosage of all the molecules (residual concentration just before the taken) and the pharmacogenetic analysis of the main metabolism pathways and the main pharmacodynamic targets.
Interventions
None listed
Sponsors
University Hospital, Lille
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Epileptic patients who required a treatment adaptation
Exclusion criteria
* patients unable to give reliable information and without caregiver * pregnancy * Severe comorbidity, which would impede interpretation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical global impression of the patient | 3 months | Clinical global impression assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of seizure | 3 months | recorded on the agenda of patients |
| Quality of life | 3 months | Analyse with the Quality Of Life In Epilepsy Questionnaire |
| Adverse events | 3 months | reported by the patients with a particular attention to attention and concentration worsening on interview |
| Concentration of the anti epileptic drug | 3 months | plasmatic drug concentration will be systematically |
| Pharmacogenetics of the uridine 5'-diphosphate glucuronosyltransférases (UGT1A1, UGT2B7, UGT1A4) | 3 months | the metabolism pathways of the drug |
| Pharmacogenetics of the Cytochrome P450 (2D6, 2C9, 2C19) | 3 months | the metabolism pathways of the drug |
| Depression inventory for epilepsy | 3 months | Neurological Disorders Depression Inventory for Epilepsy |
Countries
France
Outcome results
None listed