Precision Medicine in the Treatment of Epilepsy
ConditionEpilepsy
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age16-55
SponsorGitte Moos Knudsen
About this trial
Primary objectives:
The purpose of this study is to identify single and composite biomarkers (from neuroimaging, electrophysiological, and non-imaging biological measures), clinical measures (from cognitive, psychometric, and behavioral test scores), and risk/protective factors (e.g., from medical history, socioeconomic status, coping, lifestyle) that can:
1. Predict antiseizure medication (ASM) treatment outcome, psychiatric, cognitive, or behavioral comorbidities, and quality of life in newly diagnosed epilepsy patients (Cohort II-III). 2. Predict a second epileptic seizure/epilepsy diagnosis and behavioral, cognitive, psychiatric dysfunction and quality of life in patients after a first epileptic seizure (Cohort I).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
No history of current or past psychiatric or other major medical conditions
Disqualifiers
Current or previous neurological disease, severe somatic disease, or consumption of medical drugs likely to influence the test results
Non-fluent in Danish or pronounced visual or auditory impairments
Current or past learning disability
Pregnancy or lactation (females)
Trial population
This study consists of three patients cohorts: In Cohort I, we will include a total of 200 patients (≥16 years old) who have been referred to clinical care after experiencing their first epileptic seizure, but do not fulfill the diagnostic criteria for epilepsy. In Cohort II, we will include a total of 150 newly diagnosed epilepsy patients (≥16 years old), with the expectation that at least 70 patients from Cohort I will move into Cohort II during the observational period. Additionally, a subset of approximately 45 adult patients (≥18 years old) from Cohort II with focal onset seizures will be enrolled in Cohort III. We will also collect data from 50 healthy subjects to compare group differences at baseline.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Levetiracetam
DrugHealthy subjects and patients in Cohort III will undergo a 120 min. \[11C\]-UCB-J PET-MR brain scan followed by intravenous administration of levetiracetam after approx. 60 min. in a displacement paradigm. Before, during and after the intervention arterial spin labeling and resting-state functional MRI will be acquired. To measure the radiolabelled tracer's arterial input function, including its radiolabelled metabolites, blood samples will be drawn during the PET scan from an arterial catheter. The selected regions for the primary analyses are the epileptogenic lesion(s) (patients) and the neocortex, hippocampus, entorhinal cortex, fusiform gyrus, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, striatum, anterior cingulate cortex and amygdala. \[11C\]-UCB-J binding, volume of distribution and SV2A occupancy will be quantified by analyzing the PET images with well-validated kinetic models.
Levetiracetam Tablets
DrugPatients in Cohort II will be randomized to treatment with an ASM (levetiracetam) in accordance with standard treatment procedures. The patients will enter a 4 weeks titration period receiving increasing doses. During weeks 5-30, patients will enter an evaluation period where the dose can be increased (continued seizures) or decreased (adverse reactions). In cases of unacceptable seizure control and/or intolerable adverse reactions; shift to lamotrigine arm.
Lamotrigine tablet
DrugPatients in Cohort II will be randomized to treatment with an ASM (lamotrigine) in accordance with standard treatment procedures. The patients will enter a 6 weeks titration period receiving increasing doses. During weeks 5-30, patients will enter an evaluation period where the dose can be increased (continued seizures) or decreased (adverse reactions). In cases of unacceptable seizure control and/or intolerable adverse reactions; shift to levetiracetam arm.
Treatment groups
550 Participants
are divided into 4 treatment groupsGroup A: Healthy Controls1 intervention
Group B: Cohort I0 interventions
Group C: Cohort II2 interventions
Group D: Cohort III1 intervention
Trial outcomes
Primary outcomes
1
Categorical effect of anti-seizure medication (ASM) on treatment outcome (Cohort II-III).
1\) Seizure-free within six months after starting ASM treatment and remained seizure-free for at least one year (last observed seizure within the six months after starting ASM treatment); 2) Seizure-free more than six months after starting ASM treatment and the seizure-free period lasts at least one year; 3) Fluctuations with both seizure-freedom and seizure-relapse; or 4) Never seizure-free for a year at the third- and fifth-year follow-up timepoint.
Time frame
As change over time from the ASM evaluation period (after 4-7 weeks titration period) to six months, one, three and five years after for patients in cohort II-III.2
Categorical effect of a second seizure/epilepsy diagnosis for patients in Cohort I.
The proportion of patients in Cohort I with one epileptic seizure who become diagnosed with epilepsy.
Time frame
As change over time of epilepsy diagnosis at six months, one, three and five years after inclusion of patients in Cohort I.Secondary outcomes
1
Continuous treatment outcome using a seizure severity index (Cohort II-III).
Treatment outcome as percentage change in the Seizure Severity Questionnaire (SSQ).
Time frame
As a monthly change over time from the ASM evaluation period (after 4-7 weeks titration period) to one, three and five years after for patients in cohort II-III.2
Continuous treatment outcome rating adverse events (Cohort II-III).
Treatment outcome as percentage change in the Liverpool Adverse Event Profile (LAEP).
Time frame
As a monthly change over time from baseline and one, three and five years after inclusion for patients in cohort II-III.3
Continuous treatment outcome rating impression of change (Cohort II-III).
Treatment outcome as percentage change in in Patient's Global Impression of Change (PGIC).
Time frame
As a monthly change over time from the ASM evaluation period (after 4-7 weeks titration period) to one, three and five years after for patients in cohort II-III.4
A continuous rating of depression diagnosis (Cohort I-III and healthy).
Percentage change in Major Depression Inventory (MDI).
Time frame
At baseline between groups (HCs and patients) and as change over time from baseline to one, three and five years after inclusion for patients in cohort I-III.Other outcomes
1
Continuous treatment outcome rating state aggression (Cohort II-III and healthy).
Treatment outcome as percentage change in the State-Trait Anger Expression Inventory 2 (STAXI-2).
Time frame
At baseline between groups (HCs and patients) and as a monthly change over time from baseline and one, three and five years after inclusion for patients in cohort II-III.2
Continuous treatment outcome rating trait aggression (Cohort II-III and healthy).
Treatment outcome as percentage change in the Aggression Questionnaire (AQ).
Time frame
At baseline between groups (HCs and patients) and as change over time from baseline to one, three and five years after inclusion for patients in cohort II-III.3
Continuous treatment outcome as a measure of self-management of epilepsy (Cohort II-III).
Treatment outcome as percentage change in the Epilepsy Self-management Scale.
Time frame
As change over time from baseline to one, three and five years after inclusion for patients in cohort II-III.4
Continuous treatment outcome as a measure of expectations to treatment outcome (Cohort II-III).
Treatment outcome as percentage change in the Epilepsy Outcome Expectancy Scale.
Time frame
As change over time from baseline to one, three and five years after inclusion for patients in cohort II-III.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Gitte Moos Knudsen
Lead sponsor
Rigshospitalet, Denmark
Sponsor institution
Source ClinicalTrials.gov