Precision Medicine in the Treatment of Epilepsy

Condition(s) studied

Investigational drug(s) / intervention(s)

Levetiracetam: Healthy 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: Patients 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: Patients 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.

Study summary

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

Primary outcome measure(s)

• Categorical effect of anti-seizure medication (ASM) on treatment outcome (Cohort II-III). — 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.
  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.
• Categorical effect of a second seizure/epilepsy diagnosis for patients in Cohort I. — As change over time of epilepsy diagnosis at six months, one, three and five years after inclusion of patients in Cohort I.
  The proportion of patients in Cohort I with one epileptic seizure who become diagnosed with epilepsy.

Trial sites (1)

On this site

More Gitte Moos Knudsen trials in Denmark

Other trials for the same condition