RECRUITINGOBSERVATIONAL

Precision Medicine in the Treatment of Epilepsy

The BrainDrugs-Epilepsy Study: A Prospective Open-label Cohort Precision Medicine Study in Epilepsy

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).

Who May Be Eligible (Plain English)

Inclusion Criteria for healthy subjects: - No history of current or past psychiatric or other major medical conditions Exclusion Criteria for healthy subjects: - 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) - Participation in experiments with radioactivity (\>10 mSv) within the last year or significant occupational exposure to radioactivity - Contraindications for MRI (pacemaker, metal implants, etc.) - Severe head injury - Alcohol or drug abuse - Drug use other than tobacco and alcohol within the last 30 days - Hash \> 50 x lifetime - Drugs \> 10 x lifetime (for each substance) - Current psychoactive medication - Any current or former primary psychiatric disorder (Axis I WHO ICD-10 diagnostic classification) Inclusion Criteria for patients: - Cohort I-II: Age between 16 and 55 years - Cohort III: Age between 18 and 55 years - Cohort I: Semiology of first seizure raises a strong suspicion of epilepsy but do not fulfill International League Against Epilepsy (ILAE) diagnostic criteria - Cohort II-III: Diagnosed with epilepsy according to ILAE criteria - Cohort III: Epileptogenic lesion on MRI concordant with seizure semiology and/or EEG Exclusion criteria for patients: - Cohort I-III: Life expectancy \< 10 years - Cohort I-III: Known genetic syndromes, psychomotor retardation or disease associated with gross morphological brain changes such as brain tumor, major stroke or major traumatic brain injury - Cohort I-III: Body weight less than 40 kg - Cohort I-III: Reduced kidney function (i.e., glomerular filtration rate (GFR) \< 80 ml/min or 50 ml/min for patients 16-17 years old or ≥18 years old, respectively), - Cohort I-III: Moderate reduced liver function ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria for healthy subjects: * No history of current or past psychiatric or other major medical conditions Exclusion Criteria for healthy subjects: * 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) * Participation in experiments with radioactivity (\>10 mSv) within the last year or significant occupational exposure to radioactivity * Contraindications for MRI (pacemaker, metal implants, etc.) * Severe head injury * Alcohol or drug abuse * Drug use other than tobacco and alcohol within the last 30 days * Hash \> 50 x lifetime * Drugs \> 10 x lifetime (for each substance) * Current psychoactive medication * Any current or former primary psychiatric disorder (Axis I WHO ICD-10 diagnostic classification) Inclusion Criteria for patients: * Cohort I-II: Age between 16 and 55 years * Cohort III: Age between 18 and 55 years * Cohort I: Semiology of first seizure raises a strong suspicion of epilepsy but do not fulfill International League Against Epilepsy (ILAE) diagnostic criteria * Cohort II-III: Diagnosed with epilepsy according to ILAE criteria * Cohort III: Epileptogenic lesion on MRI concordant with seizure semiology and/or EEG Exclusion criteria for patients: * Cohort I-III: Life expectancy \< 10 years * Cohort I-III: Known genetic syndromes, psychomotor retardation or disease associated with gross morphological brain changes such as brain tumor, major stroke or major traumatic brain injury * Cohort I-III: Body weight less than 40 kg * Cohort I-III: Reduced kidney function (i.e., glomerular filtration rate (GFR) \< 80 ml/min or 50 ml/min for patients 16-17 years old or ≥18 years old, respectively), * Cohort I-III: Moderate reduced liver function * Cohort I-III: Cardiac conduction disorders (e.g., Brugada syndrome, long QT-syndrome) * Cohort I-III: Medication incompatible with study aims or causing interactions with the administered levetiracetam or lamotrigine therapy (e.g., SV2A binding agents, monoamine oxidase inhibitors, fluvoxamin, methotrexate, benzodiazepines, phenobarbital, carbamazepine, valproate, regular use of other ASMs) * Contraindication for MRI (e.g., magnetic implants, pacemaker) * Inability to complete PET (Cohort III) or MRI scans (Cohort I-III) (e.g., claustrophobia, issues with back pain) * Cohort III: Exposure to radioactivity \>10 mSv within the last year or significant occupational exposure to radioactivity * Pregnancy or lactation * Cohort I-III: Non-fluency in Danish or pronounced visual or auditory impairments or severe intellectual disability * Cohort I-III: Current or previous alcohol or drug abuse

Treatments Being Tested

DRUG

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.

DRUG

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.

DRUG

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.

Locations (1)

Neurobiology Research Unit, Rigshospitalet

Copenhagen, Denmark