Ignite Creation Date:
2024-05-06 @ 5:51 PM
Last Modification Date:
2024-10-26 @ 2:36 PM
Study NCT ID:
NCT05450822
Status:
RECRUITING
Last Update Posted:
2024-04-11
First Post:
2022-07-05
Brief Title:
Precision Medicine in the Treatment of Epilepsy
Sponsor:
Gitte Moos Knudsen
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
The BrainDrugs-Epilepsy Study A Prospective Open-label Cohort Precision Medicine Study in Epilepsy
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BDE
Brief 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 riskprotective factors eg 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 seizureepilepsy diagnosis and behavioral cognitive psychiatric dysfunction and quality of life in patients after a first epileptic seizure Cohort I
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 riskprotective factors eg 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 seizureepilepsy diagnosis and behavioral cognitive psychiatric dysfunction and quality of life in patients after a first epileptic seizure Cohort I
Detailed Description:
Material and methods
The BrainDrugs Epilepsy Study will be conducted as an open longitudinal prospective cohort study The study consists of three patient cohorts
Cohort I includes patients with a first epileptic seizure who will undergo basic clinical cognitive psychometric and biological blood assessment as well as electroencephalography EEG and Magnetic Resonance Imaging MRI neuroimaging
Cohort II includes patients newly diagnosed with epilepsy who will undergo additional clinical cognitive psychometric and biological blood and stool assessment as well as EEG and MRI neuroimaging
Cohort III includes a subset of patients from Cohort II who they also undergo Positron Emission Tomography PET synaptic vesicle glycoprotein 2A SV2A neuroimaging
Data from healthy controls will be collected the investigative program for whom will be similar to that of Cohort III
After completing the baseline investigation program patients diagnosed with epilepsy will start ASM treatment with lamotrigine or levetiracetam in accordance with standard treatment procedures If the first ASM does not lead to seizure-freedom the patients will be offered to switch to the other Patients will be monitored every three months in the epilepsy outpatient clinic or by video or telephone consultations For daily monitoring a digital solution will be used including a mobile app for patients and a web dashboard for health professionals
The mobile app contains a study module with content tailor-made for the BrainDrugs Epilepsy Study Patients will be instructed to use the app once daily to register compliance and disease progression Patients will complete monthly questionnaires NDDI-E GAD-7 LAEP PGIC SSQ STAXI-2 and WHO-5 through the app tracking depressive symptoms anxiety adverse reactions treatment response seizure frequency and severity aggression and quality of life
The investigators aim to include a total of 350 patients and 50 healthy subjects during the first three years of the study All patients will be followed for five years In addition data from Danish health registries and electronic patient records will be used to characterize patients both retrospectively eg information about birth complications and prospectively eg clinical status during the study period
In Cohort I investigators 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 fulfil the diagnostic criteria for epilepsy In Cohort II investigators will include a total of 150 newly diagnosed patients with epilepsy 16 years old During the observational period investigators expect at least 70 patients from Cohort I to be diagnosed with epilepsy upon experiencing their second epileptic seizure These patients will subsequently be included in Cohort II Lastly Cohort III will be a subset of approximately 45 adult patients 18 years old from Cohort II with focal onset seizures who will undergo investigation with PET
After inclusion in the study the patients will undergo an examination program at baseline and follow-up 1 3 and 5 years after inclusion that includes a study nurse interview with setup of the mobile app neuropsychiatric interview and examination neuropsychological tests and self-report questionnaires high density EEG MRI brain scan including T1 T2 fluid-attenuated inversion recovery FLAIR diffusion tensor imaging DTI arterial spin labeling ASL and functional magnetic resonance imaging fMRI and blood and urine samples as well as gut microbiome samples Cohort II-III In addition adult patients in Cohort III will undergo a 11C-UCB-J PET brain scan followed by intravenous administration of levetiracetam LEV in a displacement paradigm
For patients in Cohort III treated with LEV if both symptoms and extended examinations are compatible with either 1 the development of an epilepsy-related comorbidity 2 clinically significant adverse reactions or adverse events 3 drug treatment failure or 4 drug resistance a repeated 11C-UCB-J PET brain scan will be acquired prior to change in ASM treatment
After inclusion in the study all healthy controls HCs will undergo an examination program similar to Cohort III HCs will not be followed over time The mobile app will only be used by patients
Primary hypotheses
1 Combined biomarkers from morphometric measurements eg the volume of thalamus and hippocampus cortical thickness of precentral gyri parahippocampal cortex entorhinal and fusiform gyri precuneus frontal gyri within-network resting-state functional connectivity rsfMRI whole-brain structural connectomics Diffusion Tensor Imaging DTI and functional connectivity in the theta band EEG at baseline can be used to predict the chance of a recurrent seizure Cohort I
2 Combined biomarkers from morphometric measurements eg the volume of amygdala and hippocampus cortical thickness of orbitofrontal cortex resting-state functional connectivity in the anterior cingulate cortex between prefrontal-limbic systems angular gyrus temporal lobe precuneus cerebellum default mode network and executive control network rsfMRI structural connectivity between temporal lobe the limbic system and orbitofrontal cortex DTI and functional connectivity in the anterior cingulate cortex frontal and occipital alpha asymmetry and theta current source density in the anterior cingulate cortex EEG at epilepsy diagnosis can be used to predict the risk of developing drug-failure and epilepsy-related comorbidities Cohort II-III
3 Cerebral 11C-UCB-J binding at baseline both globally and in primary volumes of interest ie hippocampus entorhinal cortex fusiform gyrus dorsolateral prefrontal cortex ventrolateral prefrontal cortex orbitofrontal cortex striatum anterior cingulate cortex and amygdala correlate negatively with epilepsy-related comorbidities eg depressive episodes and cognitive deficits Cohort III and healthy
4 Cerebral 11C-UCB-J PET SV2A occupancy following a displacement paradigm with levetiracetam is associated with a decrease in cerebral blood flow in the epileptogenic lesionss patients and in primary volumes of interest ie hippocampus entorhinal cortex fusiform gyrus dorsolateral prefrontal cortex ventrolateral prefrontal cortex orbitofrontal cortex striatum anterior cingulate and amygdala cortex in healthy controls and in patients who become seizure free with levetiracetam treatment Cohort III and healthy
The BrainDrugs Epilepsy Study will be conducted as an open longitudinal prospective cohort study The study consists of three patient cohorts
Cohort I includes patients with a first epileptic seizure who will undergo basic clinical cognitive psychometric and biological blood assessment as well as electroencephalography EEG and Magnetic Resonance Imaging MRI neuroimaging
Cohort II includes patients newly diagnosed with epilepsy who will undergo additional clinical cognitive psychometric and biological blood and stool assessment as well as EEG and MRI neuroimaging
Cohort III includes a subset of patients from Cohort II who they also undergo Positron Emission Tomography PET synaptic vesicle glycoprotein 2A SV2A neuroimaging
Data from healthy controls will be collected the investigative program for whom will be similar to that of Cohort III
After completing the baseline investigation program patients diagnosed with epilepsy will start ASM treatment with lamotrigine or levetiracetam in accordance with standard treatment procedures If the first ASM does not lead to seizure-freedom the patients will be offered to switch to the other Patients will be monitored every three months in the epilepsy outpatient clinic or by video or telephone consultations For daily monitoring a digital solution will be used including a mobile app for patients and a web dashboard for health professionals
The mobile app contains a study module with content tailor-made for the BrainDrugs Epilepsy Study Patients will be instructed to use the app once daily to register compliance and disease progression Patients will complete monthly questionnaires NDDI-E GAD-7 LAEP PGIC SSQ STAXI-2 and WHO-5 through the app tracking depressive symptoms anxiety adverse reactions treatment response seizure frequency and severity aggression and quality of life
The investigators aim to include a total of 350 patients and 50 healthy subjects during the first three years of the study All patients will be followed for five years In addition data from Danish health registries and electronic patient records will be used to characterize patients both retrospectively eg information about birth complications and prospectively eg clinical status during the study period
In Cohort I investigators 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 fulfil the diagnostic criteria for epilepsy In Cohort II investigators will include a total of 150 newly diagnosed patients with epilepsy 16 years old During the observational period investigators expect at least 70 patients from Cohort I to be diagnosed with epilepsy upon experiencing their second epileptic seizure These patients will subsequently be included in Cohort II Lastly Cohort III will be a subset of approximately 45 adult patients 18 years old from Cohort II with focal onset seizures who will undergo investigation with PET
After inclusion in the study the patients will undergo an examination program at baseline and follow-up 1 3 and 5 years after inclusion that includes a study nurse interview with setup of the mobile app neuropsychiatric interview and examination neuropsychological tests and self-report questionnaires high density EEG MRI brain scan including T1 T2 fluid-attenuated inversion recovery FLAIR diffusion tensor imaging DTI arterial spin labeling ASL and functional magnetic resonance imaging fMRI and blood and urine samples as well as gut microbiome samples Cohort II-III In addition adult patients in Cohort III will undergo a 11C-UCB-J PET brain scan followed by intravenous administration of levetiracetam LEV in a displacement paradigm
For patients in Cohort III treated with LEV if both symptoms and extended examinations are compatible with either 1 the development of an epilepsy-related comorbidity 2 clinically significant adverse reactions or adverse events 3 drug treatment failure or 4 drug resistance a repeated 11C-UCB-J PET brain scan will be acquired prior to change in ASM treatment
After inclusion in the study all healthy controls HCs will undergo an examination program similar to Cohort III HCs will not be followed over time The mobile app will only be used by patients
Primary hypotheses
1 Combined biomarkers from morphometric measurements eg the volume of thalamus and hippocampus cortical thickness of precentral gyri parahippocampal cortex entorhinal and fusiform gyri precuneus frontal gyri within-network resting-state functional connectivity rsfMRI whole-brain structural connectomics Diffusion Tensor Imaging DTI and functional connectivity in the theta band EEG at baseline can be used to predict the chance of a recurrent seizure Cohort I
2 Combined biomarkers from morphometric measurements eg the volume of amygdala and hippocampus cortical thickness of orbitofrontal cortex resting-state functional connectivity in the anterior cingulate cortex between prefrontal-limbic systems angular gyrus temporal lobe precuneus cerebellum default mode network and executive control network rsfMRI structural connectivity between temporal lobe the limbic system and orbitofrontal cortex DTI and functional connectivity in the anterior cingulate cortex frontal and occipital alpha asymmetry and theta current source density in the anterior cingulate cortex EEG at epilepsy diagnosis can be used to predict the risk of developing drug-failure and epilepsy-related comorbidities Cohort II-III
3 Cerebral 11C-UCB-J binding at baseline both globally and in primary volumes of interest ie hippocampus entorhinal cortex fusiform gyrus dorsolateral prefrontal cortex ventrolateral prefrontal cortex orbitofrontal cortex striatum anterior cingulate cortex and amygdala correlate negatively with epilepsy-related comorbidities eg depressive episodes and cognitive deficits Cohort III and healthy
4 Cerebral 11C-UCB-J PET SV2A occupancy following a displacement paradigm with levetiracetam is associated with a decrease in cerebral blood flow in the epileptogenic lesionss patients and in primary volumes of interest ie hippocampus entorhinal cortex fusiform gyrus dorsolateral prefrontal cortex ventrolateral prefrontal cortex orbitofrontal cortex striatum anterior cingulate and amygdala cortex in healthy controls and in patients who become seizure free with levetiracetam treatment Cohort III and healthy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None