Clinical trial NCT02883712: Study of Predictors of Response to Anti Epilepsy in Epilepsy
Official title: Study of Predictors of Response to Anti Epilepsy in Epilepsy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Seizure
Keywords: epilepsy
pharmacoresistant
antiepileptic drug
pharmacokinetic
pharmacodynamic
pharmacogenetic
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-08-30
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients referred to our center with epilepsy (pharmacoresistant or pharmacosensitive)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical global impression of the patient
timeFrame: 3 months
Secondary outcomes:
measure: Number of seizure
timeFrame: 3 months
measure: Quality of life
timeFrame: 3 months
measure: Adverse events
timeFrame: 3 months
measure: Concentration of the anti epileptic drug
timeFrame: 3 months
measure: Pharmacogenetics of the uridine 5'-diphosphate glucuronosyltransférases (UGT1A1, UGT2B7, UGT1A4)
timeFrame: 3 months
measure: Pharmacogenetics of the Cytochrome P450 (2D6, 2C9, 2C19)
timeFrame: 3 months
measure: Depression inventory for epilepsy
timeFrame: 3 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro, CHRU de Lille
Study officials:
affiliation: University Hospital, Lille
name: David DEVOS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: