Study of Predictors of Response to Anti Epilepsy in Epilepsy (RESISTANT)

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.

Study Overview

• Status: Terminated
• Conditions: Seizure

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.

• Study Type: Observational
• Enrollment (Actual): 155

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hopital Roger Salengro, CHRU de Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients referred to our center with epilepsy (pharmacoresistant or pharmacosensitive)

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical global impression of the patient	Clinical global impression assessment	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of seizure	recorded on the agenda of patients	3 months
Quality of life	Analyse with the Quality Of Life In Epilepsy Questionnaire	3 months
Adverse events	reported by the patients with a particular attention to attention and concentration worsening on interview	3 months
Concentration of the anti epileptic drug	plasmatic drug concentration will be systematically	3 months
Pharmacogenetics of the uridine 5'-diphosphate glucuronosyltransférases (UGT1A1, UGT2B7, UGT1A4)	the metabolism pathways of the drug	3 months
Pharmacogenetics of the Cytochrome P450 (2D6, 2C9, 2C19)	the metabolism pathways of the drug	3 months
Depression inventory for epilepsy	Neurological Disorders Depression Inventory for Epilepsy	3 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2013
• Primary Completion (Actual): January 1, 2021
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 24, 2016
• First Posted (Estimate): August 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: epilepsy; pharmacokinetic; pharmacodynamic; antiepileptic drug; pharmacogenetic; pharmacoresistant
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures
• Other Study ID Numbers: 2011_37; 2012-A00916-37 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO