EpilepsyNCT06321822
Genetic Diagnosis and Personalized Medicine for Patients With Epilepsy
A study testing Whole exome sequencing (WES) in people with Epilepsy, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
Background Epilepsy is a common neurological disorder. It affects 50 million people worldwide and has the highest incidence in pediatric age. According to the latest classification of the ILAE (International League against Epilepsy), epilepsies are divided into lesional (symptomatic) and non-lesional/genetic forms. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Epilepsy
- What is being tested?
- Whole exome sequencing (WES)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteItaly
- Study dates
- 2 Aug 2021to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Study population: patients with epilepsy.
- Patients who meet all of the following criteria will be included:
- Patients both minors and adults diagnosed with epilepsy;
- of both sexes;
- followed at the pediatric and adult epilepsy and electroencephalography clinics of the U.O.C. Neurophysiopathology - IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico;
- Informed consent of the patient if an adult and capable of providing consent independently or of the parents or legal guardians in the case of a minor/individual not capable of providing consent independently.
- Availability of DNA samples from the patient and both natural parents;
- Prediction of high positive genetic diagnosis Patients diagnosed with epilepsy will be recruited among those followed at the pediatric and adult epilepsy and electroencephalography clinics of the U.O.C. Neurophysiopathology - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, after signing the consent.
Who cannot join
- Patients who possess at least one of the following criteria will be excluded:
- Patients arriving for evaluation with the initial suspicion of epilepsy who during the diagnostic work-up were found to be suffering from a different pathology;
- Patients who have refused consent to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Robertino Dilena, MD, +390255032406, robertino.dilena@policlinico.mi.it
About this study
Official title: Characterization of Patients With Epilepsy With an Integrated Approach of Clinical, Neurophysiological, Neuroradiological, Neuropsychological and Laboratory (Exome) Methods for Personalized Medicine
Background Epilepsy is a common neurological disorder. It affects 50 million people worldwide and has the highest incidence in pediatric age. According to the latest classification of the ILAE (International League against Epilepsy), epilepsies are divided into lesional (symptomatic) and non-lesional/genetic forms. Symptomatic causes of epilepsy may include scarring, tumors, strokes, and brain developmental disorders such as dysplasias. In approximately 30% of epilepsies a genetic cause of epilepsy can be hypothesized. Since the identification of the first epilepsy gene in 1995, over the next 25 years over 500 genes associated with epilepsy have been identified. The importance of many genes and many gene variants identified in many genes is not yet clear and the mutations identified in different genes require confirmation with functional studies and confirmation on larger series of patients. Furthermore, the genetic defect underlying many patients with epilepsy remains unknown to this day, despite a high level of gene sequencing effort.
Molecular studies on these genes have demonstrated how pathogenic variants on these genes determine a protein dysfunction that can cause neuronal hyperexcitability and pathological synchronization of neuronal networks leading to epileptic seizures and brain dysfunction. A notable complication in the field of epilepsy genetics is represented by the fact that the concept of a gene/a disease is valid only in a few cases, as there is a high phenotypic and genotypic heterogeneity so that a gene can present different types of epilepsy even within the same family. This means that there is a complex multigenic and multifactorial genetic substrate for which the impact of a specific genetic variant is conditioned by variants of other genes. This concept is particularly valid for the most common epileptic forms such as idiopathic generalized epilepsies.
Read more
The integration of genetic analysis with epileptological characterization in clinical practice is increasingly crucial in defining a clear molecular diagnosis in patients whose disease cause would otherwise remain unknown, and potentially allows avoiding other unnecessary diagnostic investigations. It is therefore expected that this will lead to optimizing clinical management and reducing overall costs over time. The genetic finding can constitute a useful biomarker for defining the outcome of the disease and for guiding clinical decisions such as the best choice of therapy. Despite the advantages, before starting the genetic testing process, patients and their family members should be informed about the ethical issues that may arise from genetic testing, the technical limitations, legal aspects and costs of genetic investigation.
Aim of the study Characterization of patients with epilepsy recruited at the Hospital Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan (Italy) and analysis with exome NGS sequencing of patients with the highest probability of genetic diagnosis with exome (use of a probability score)
Endpoints of study are the following:
- Identification of the genetic cause of the forms of genetic epilepsies with the highest probability of molecular diagnosis with exome
- Clinical-instrumental and epileptological characterization according to the ILAE classification of patients with epilepsy followed at the Fondazione IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico
- Correlation of clinical and instrumental parameters (in particular EEG and neuropsychological) of epilepsy recorded on the database with etiology, outcome and response to therapy
Read the detailed description
Study design Non-pharmacological (diagnostic) interventional, single-center, biological, observational, prospective Interventions
- Collection of clinical and instrumental data of patients with epilepsy at first outpatient visit (time 0) and at one-year follow-up: age, gender, education, age of onset of seizures, new diagnosis/check-up, type of seizure according to the ILAE classification, type of epilepsy according to the ILAE classification, frequency of epileptic seizures, etiology, for cases with a genetic/probably genetic etiology application of an ad hoc score to determine the probability of a positive outcome for exome research, neurological objectivity, presence of comorbidities, parameters of EEG background activity, parameters relating to interictal EEG anomalies, parameters relating to critical EEG anomalies, magnetic resonance parameters, therapies used, effectiveness of therapies used, side effects of therapies, duration of therapy, dosages of therapy, neuropsychological and psychological outcome (score on standard tests/questionnaires administered according to age as required by the standard of care), functional outcome expressed with the modified Rankin scale; clinical and instrumental data will also be collected for sick or healthy parents of patients with epilepsy who will be identified for the exome analysis of the trio (proband + parents) during the recruitment phase (not at follow-up), while they will not be collected sensitive data relating to the parents of patients who did not undergo an exome (observational part of the study).
- Qualitative evaluation of the EEG according to the ACNS guidelines and whenever possible through quantitative analysis of the EEG parameters at time 0 and at 1 year follow up. In the quantitative analysis, ad hoc algorithms will be used to extract the temporal and frequency domain characteristics of the EEG traces.
- Sequencing and analysis of the exome of at least 30 patients and their natural parents (plus any other first-degree relatives affected by epilepsy or genetic condition related to epilepsy) for a total of at least 90 exomes.
With the exception of WES sequencing, the other diagnostic-evaluative procedures are part of the normal clinical management of patients.
Genotype-phenotype correlations The WES will be evaluated in relation to the clinical picture on the basis of a close collaboration between clinicians (neurologists), biologists, geneticists, bioinformatics involved in the project. The acquired data will also be used to define the risk of recurrence, prognosis, monitoring of complications and identification of possible targeted treatments.
- Conditions
- Epilepsy
- Being tested
- Whole exome sequencing (WES)
- Keywords
- genetics, NGS exome sequencing, Personalized medicine, Genotype-phenotype correlation
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole exome sequencing (WES)Diagnostic test
Patient selected for genetic study will undergo blood sample collection for DNA estraction, biobank storage and WES study
| Study group | Role | What they receive |
|---|---|---|
| Epileptic Patients recruited for observational study | Experimental | Patients with epilepsy recruited for observation study. When criteria for genetic epilepsy will be met, they will undergo testing for genetic investigation through exome NGS sequencing Receives: Diagnostic Test: Whole exome sequencing (WES) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the genetic cause in patients with clinically probable genetic epilepsy using WES
Identification of the genetic cause of patients with forms of epilepsy with a high probability using of genetic etiology, selected from the cohort of epileptic patients followed at Fondazione IRCCS Ca' Ospedale Maggiore Policlinico, using WES
Measured: 1 year after enrollment
Secondary outcomes (4)
Clinical and epileptological characterization of patients with epilepsy according to ILAE seizure and epilepsy classification
Clinical and epileptological characterization according to the ILAE classification of the population of patients with epilepsy followed at the IRCCS Ca' Ospedale Maggiore Policlinico Foundation
Measured: 1 year after enrollment
Characterization of qualitative Electroencefagraphy (EEG) features of patients with the different epilepsy types
Electroencephalographic evaluation of EEG traces of patients with the different epilepsy types a structured qualitative EEG evaluation performed by a trained clinical neurophysiologist
Measured: 1 year after enrollment
Quantitative EEG (qEEG) characterization of patients with the different epilepsy types
Analysis of EEG traces of patients with the different epilepsy types using the tools of Quantitative EEG (aEEG), as Power spectrum analyses, by a trained EEG signal Engineer
Measured: 3 year after enrollment
Characterization of the clinical and instrumental features of patients with specific genetic etiology
Characterization of the clinical and instrumental features of patients with specific genetic etiology by a trained epileptologist
Measured: 1 year after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start2 Aug 2021
- Primary completion2 Aug 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robertino Dilena, MD, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06321822
- Sponsor's protocol ID
- EPIEXOME
- Status last verified
- Mar 2024
- First submitted
- 4 Mar 2024
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Patients With Epilepsy With an Integrated Approach of Clinical, Neurophysiological, Neuroradiological, Neuropsychological and Laboratory (Exome) Methods for Personalized Medicine
- ClinicalTrials.gov ID
- NCT06321822
- Acronym / sponsor ID
- EPIEXOME
- Conditions
- Epilepsy
- Keywords
- genetics, NGS exome sequencing, Personalized medicine, Genotype-phenotype correlation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 2 Aug 2021 (actual)
- Primary completion
- 2 Aug 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background Epilepsy is a common neurological disorder. It affects 50 million people worldwide and has the highest incidence in pediatric age. According to the latest classification of the ILAE (International League against Epilepsy), epilepsies are divided into lesional (symptomatic) and non-lesional/genetic forms. Symptomatic causes of epilepsy may include scarring, tumors, strokes, and brain developmental disorders such as dysplasias. In approximately 30% of epilepsies a genetic cause of epilepsy can be hypothesized. Since the identification of the first epilepsy gene in 1995, over the next 25 years over 500 genes associated with epilepsy have been identified. The importance of many genes and many gene variants identified in many genes is not yet clear and the mutations identified in different genes require confirmation with functional studies and confirmation on larger series of patients. Furthermore, the genetic defect underlying many patients with epilepsy remains unknown to this day, despite a high level of gene sequencing effort.
Molecular studies on these genes have demonstrated how pathogenic variants on these genes determine a protein dysfunction that can cause neuronal hyperexcitability and pathological synchronization of neuronal networks leading to epileptic seizures and brain dysfunction. A notable complication in the field of epilepsy genetics is represented by the fact that the concept of a gene/a disease is valid only in a few cases, as there is a high phenotypic and genotypic heterogeneity so that a gene can present different types of epilepsy even within the same family. This means that there is a complex multigenic and multifactorial genetic substrate for which the impact of a specific genetic variant is conditioned by variants of other genes. This concept is particularly valid for the most common epileptic forms such as idiopathic generalized epilepsies.
The integration of genetic analysis with epileptological characterization in clinical practice is increasingly crucial in defining a clear molecular diagnosis in patients whose disease cause would otherwise remain unknown, and potentially allows avoiding other unnecessary diagnostic investigations. It is therefore expected that this will lead to optimizing clinical management and reducing overall costs over time. The genetic finding can constitute a useful biomarker for defining the outcome of the disease and for guiding clinical decisions such as the best choice of therapy. Despite the advantages, before starting the genetic testing process, patients and their family members should be informed about the ethical issues that may arise from genetic testing, the technical limitations, legal aspects and costs of genetic investigation.
Aim of the study Characterization of patients with epilepsy recruited at the Hospital Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan (Italy) and analysis with exome NGS sequencing of patients with the highest probability of genetic diagnosis with exome (use of a probability score)
Endpoints of study are the following:
- Identification of the genetic cause of the forms of genetic epilepsies with the highest probability of molecular diagnosis with exome
- Clinical-instrumental and epileptological characterization according to the ILAE classification of patients with epilepsy followed at the Fondazione IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico
- Correlation of clinical and instrumental parameters (in particular EEG and neuropsychological) of epilepsy recorded on the database with etiology, outcome and response to therapy
Detailed description
Study design Non-pharmacological (diagnostic) interventional, single-center, biological, observational, prospective Interventions
- Collection of clinical and instrumental data of patients with epilepsy at first outpatient visit (time 0) and at one-year follow-up: age, gender, education, age of onset of seizures, new diagnosis/check-up, type of seizure according to the ILAE classification, type of epilepsy according to the ILAE classification, frequency of epileptic seizures, etiology, for cases with a genetic/probably genetic etiology application of an ad hoc score to determine the probability of a positive outcome for exome research, neurological objectivity, presence of comorbidities, parameters of EEG background activity, parameters relating to interictal EEG anomalies, parameters relating to critical EEG anomalies, magnetic resonance parameters, therapies used, effectiveness of therapies used, side effects of therapies, duration of therapy, dosages of therapy, neuropsychological and psychological outcome (score on standard tests/questionnaires administered according to age as required by the standard of care), functional outcome expressed with the modified Rankin scale; clinical and instrumental data will also be collected for sick or healthy parents of patients with epilepsy who will be identified for the exome analysis of the trio (proband + parents) during the recruitment phase (not at follow-up), while they will not be collected sensitive data relating to the parents of patients who did not undergo an exome (observational part of the study).
- Qualitative evaluation of the EEG according to the ACNS guidelines and whenever possible through quantitative analysis of the EEG parameters at time 0 and at 1 year follow up. In the quantitative analysis, ad hoc algorithms will be used to extract the temporal and frequency domain characteristics of the EEG traces.
- Sequencing and analysis of the exome of at least 30 patients and their natural parents (plus any other first-degree relatives affected by epilepsy or genetic condition related to epilepsy) for a total of at least 90 exomes.
With the exception of WES sequencing, the other diagnostic-evaluative procedures are part of the normal clinical management of patients.
Genotype-phenotype correlations The WES will be evaluated in relation to the clinical picture on the basis of a close collaboration between clinicians (neurologists), biologists, geneticists, bioinformatics involved in the project. The acquired data will also be used to define the risk of recurrence, prognosis, monitoring of complications and identification of possible targeted treatments.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epileptic Patients recruited for observational study | Experimental | Diagnostic Test: Whole exome sequencing (WES)Patients with epilepsy recruited for observation study. When criteria for genetic epilepsy will be met, they will undergo testing for genetic investigation through exome NGS sequencing |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Study population: patients with epilepsy.
- Patients both minors and adults diagnosed with epilepsy;
- of both sexes;
- followed at the pediatric and adult epilepsy and electroencephalography clinics of the U.O.C. Neurophysiopathology - IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico;
- Informed consent of the patient if an adult and capable of providing consent independently or of the parents or legal guardians in the case of a minor/individual not capable of providing consent independently.
Key exclusion criteria (3 listed)
- Patients who possess at least one of the following criteria will be excluded:
- Patients arriving for evaluation with the initial suspicion of epilepsy who during the diagnostic work-up were found to be suffering from a different pathology;
- Patients who have refused consent to participate in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole exome sequencing (WES)Patient selected for genetic study will undergo blood sample collection for DNA estraction, biobank storage and WES study | Diagnostic test | Epileptic Patients recruited for observational study |
Primary outcome
Identification of the genetic cause in patients with clinically probable genetic epilepsy using WES
Time frame: 1 year after enrollment
Identification of the genetic cause of patients with forms of epilepsy with a high probability using of genetic etiology, selected from the cohort of epileptic patients followed at Fondazione IRCCS Ca' Ospedale Maggiore Policlinico, using WES
4 secondary outcomes
Clinical and epileptological characterization of patients with epilepsy according to ILAE seizure and epilepsy classification
Time frame: 1 year after enrollment
Characterization of qualitative Electroencefagraphy (EEG) features of patients with the different epilepsy types
Time frame: 1 year after enrollment
Quantitative EEG (qEEG) characterization of patients with the different epilepsy types
Time frame: 3 year after enrollment
Characterization of the clinical and instrumental features of patients with specific genetic etiology
Time frame: 1 year after enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Individual participant dataSharing planned: No
Related trials for Epilepsy
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Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robertino Dilena, MD principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Whole exome sequencing (WES) in people with Epilepsy, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federica Massacesi (+390255032982, federica.massacesi@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of the genetic cause in patients with clinically probable genetic epilepsy using WES (time frame: 1 year after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.