Focal EpilepsyBIOEPINCT05278221
TMS Combined With EEG/EMG as a Biomarker Predicting Antiepileptic Drug Response
A study testing Software EstimLT in people with Focal Epilepsy, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
Ιn the present study (BIOEPI), the following three hypotheses will be investigated: 1. The proposed TMS-EEG / EMG protocol (which includes software for calculating the cerebral cortex stimulation threshold) in combination with advanced signal analysis and data mining methods will allow the detection of the effect of… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Focal Epilepsy
- What is being tested?
- Software EstimLT
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteGreece
- Study dates
- 1 Aug 2022to 31 Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General criteria:
- Adult volunteers aged 18-65 years
- Able to provide informed consent
- Meet the criteria of the attached TMS safety questionnaire (Rossi et al, 2011). It is clarified that: a) criterion 1 does not apply to the group of patients and b) a positive answer to criteria 5, 6, 8, 9 \& 10 excludes inclusion in the study while the other answers are evaluated by the investigator.
- Specific criteria:
- The specific criteria per group of study participants are as follows:
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- Patient Group:
- Adult patients, 18-65 years of age, suffering from focal epilepsy, as evidenced by clinical and EEG features.
- All patients continue suffering from seizures despite treatment with 1-2 concomitant AEDs (with vagal nerve stimulation counting as an AED). In order to be eligible, patients should be suffering from simple partial seizures (SPS) and a motor component or complex partial seizures (CPS) with or without secondary generalization (sGS). Patients should report at least three seizures during the 12 weeks of Historical Baseline.
- Patients are required to be Lacosamide and Brivaracetam-naive and, in the latter case, not taking concomitant Levetiracetam.
- Patients are about to commence treatment with Lacosamide or Brivaracetam, as per the treating physician's orders. It is stressed that the decision to prescribe Lacosamide or Brivaracetam is made by the patient's treating physician totally independently from participation in the current study.
- Epilepsies of genetic or unknown aetiology (patients with hippocampal sclerosis can be included). The epileptic patients will be a convenience sample recruited at the Epilepsy Outpatient Clinic of the University General Hospital of Thessaloniki "AHEPA".
- Healthy control group:
- Adult, healthy volunteers, 18-65 years of age
Who cannot join
- The specific criteria per group of study participants are as follows:
- Patient Group:
- The presence of Central Nervous System "CNS" disorders other than epilepsy on history or examination
- Comorbid psychiatric or medical conditions that may compromise the ability of the individuals to participate in the study
- EEG evidence of generalized epilepsy.
- Uncountable seizures due to clustering.
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- Use of centrally acting drugs other than AEDs.
- Pregnancy or planned pregnancy prior to the index test.
- Healthy control group:
- Presence of medical or psychiatric conditions that may interfere with the procedures.
- Contraindications to TMS (i.e. pregnancy, presence of heart pacemakers, metal objects etc).
- History of adverse reactions to pharmacological agents.
- History of alcohol or nicotine abuse or use of any other centrally acting drug.
- Participation in another clinical trial in the previous 8 weeks.
- Pregnancy or planned pregnancy prior to the index test.
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
Prof. Vasilios Kimiskidis
Thessaloniki, Thessaloniki, 546 36
Vasilios Kimiskidis, 0030 2310 994667, kimiskid@auth.gr
About this study
Official title: Development and Optimization of Transcranial Magnetic Stimulation (TMS) Combined With EEG/EMG as a Biomarker Predicting Response to Antiepileptic Drugs
Ιn the present study (BIOEPI), the following three hypotheses will be investigated:
- The proposed TMS-EEG / EMG protocol (which includes software for calculating the cerebral cortex stimulation threshold) in combination with advanced signal analysis and data mining methods will allow the detection of the effect of antiepileptic drugs (AED) with different mechanisms of action (lacosamide \& brivaracetam) in the Central Nervous System under healthy and pathological conditions (Epilepsy).
- AED-induced changes in selected TMS-EEG / EMG features predict the clinical response of individual epileptic patients to AED.
- AED-induced changes in selected TMS-EEG / EMG features may predict cognitive side effects.
Read the detailed description
The overarching objective of this study is to develop a combined TMS-EEG/EMG protocol so as to explore the effects of AEDs on cortical excitability and obtain novel electrophysiological biomarkers which could help predict the response of epileptic patients to AEDs, in line with the principles of personalized medicine. In order to achieve the overarching objective, we will perform a Diagnostic Clinical Performance Study, (FDA 2013) with the following specific objectives.
Primary Objective 1: To investigate whether TMS-EEG/EMG biomarkers can predict the response of patients with focal epilepsy to AEDs (Lacosamide \& Brivaracetam).
Secondary Objective 1: Development, testing and validation of novel TMS-EEG/EMG stimulation and multi-level data analysis protocols, incorporating advanced methods of signal analysis, connectivity, complexity, and propagation across the cortical mantle.
Secondary Objective 2: Investigating the sensitivity of TMS-EEG/EMG biomarkers for detecting changes in brain physiology in healthy subjects and patients with focal epilepsy.Secondary Objective 3: Investigating whether TMS-EEG / EMG biomarkers may predict cognitive deficits in patients with focal epilepsy.
- Conditions
- Focal Epilepsy
- Being tested
- Software EstimLT
- Keywords
- epilepsy, medical device
- Medical subject headings
- Epilepsies, Partial, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Software EstimLTDevice
Healthy volunteers will receive a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo and then the software will be tested
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | Other | Each healthy volunteer during Part I of the study will receive every 2 weeks a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo. All healthy volunteers will perform tests using the new software that combines Transcranial Magnetic Stimulation Combined With EEG/EMG, Receives: Device: Software EstimLT |
| Patients with focal epilepsy | Other | Patients during Part II, will receive the treatment according to the treating physician's discretion, regardless of the protocol, either with Lacosamide, 300 mg p.o. or Brivaracetam, 100 mg p.o. All patients will perform tests using the new software that combines Transcranial Magnetic Stimulation Combined With EEG/EMG, Receives: Device: Software EstimLT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic accuracy of TMS Combined With EEG/EMG for predicting response to AEDs
The Primary Outcome Measure is the diagnostic accuracy (calculated as the number of true positives + true negatives)/(number of true positives + true negatives + false positives + false negatives) of the index test for predicting response to AEDs (defined as reduction of seizure frequency by 50% or more during the maintenance period in comparison to baseline).
The primary efficacy endpoint will be assessed in the combined groups of responders (LAC+BRV) and non-responders (LAC+BRV) because the starting hypothesis is that response to AEDs will be associated with alterations in TMS-EEG/EMG biomarkers.
Measured: 9 months
Secondary outcomes (3)
PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for predicting response to AEDs
Positive Predictive Value (PPV), Negative Predictive Value (NPV), positive likelihood ratio (LR+) \& negative likelihood ratio (LR-) of TMS Combined With EEG/EMG for predicting response to AEDs (defined as reduction of seizure frequency by 50% or more).
Measured: Through study completion, an average of 2 years
Accuracy, PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for other measures of response to AEDs
Accuracy, PPV, NPV, positive likelihood ratio (LR+) \& negative likelihood ratio (LR-) of TMS Combined With EEG/EMG for other measures of response to AEDs (i.e. percent seizure reduction, seizure freedom, time to n th (n=1,5th,10th) seizure).
Measured: Through study completion, an average of 2 years
Accuracy of TMS Combined With EEG/EMG for predicting AED-induced side-effects
Accuracy of TMS Combined With EEG/EMG for predicting AED-induced cognitive side-effects and other study-emergent Adverse Events
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2022
- Study start1 Aug 2022
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal EpilepsyStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study has 2 parts; part I that includes healthy volunteers and part II that includes patients with focal epilepsy. Each healthy volunteer will participate in three sessions every 2 weeks and will receive a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo. Patients in part II will receive either Lacosamide, 300 mg p.o. or Brivaracetam, 100 mg p.o. All participants will perform a test using the tested software that combines a Transcranial Magnetic Stimulation with EEG/EMG
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05278221
- Sponsor's protocol ID
- BIOEPI
- Acronym
- BIOEPI
- Status last verified
- Mar 2023
- First submitted
- 10 Feb 2022
- Last updated
- 10 Mar 2023
- 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 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development and Optimization of Transcranial Magnetic Stimulation (TMS) Combined With EEG/EMG as a Biomarker Predicting Response to Antiepileptic Drugs
- ClinicalTrials.gov ID
- NCT05278221
- Acronym / sponsor ID
- BIOEPI / BIOEPI
- Conditions
- Focal Epilepsy
- Keywords
- epilepsy, medical device
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 14 Mar 2022 (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.
Ιn the present study (BIOEPI), the following three hypotheses will be investigated:
- The proposed TMS-EEG / EMG protocol (which includes software for calculating the cerebral cortex stimulation threshold) in combination with advanced signal analysis and data mining methods will allow the detection of the effect of antiepileptic drugs (AED) with different mechanisms of action (lacosamide \& brivaracetam) in the Central Nervous System under healthy and pathological conditions (Epilepsy).
- AED-induced changes in selected TMS-EEG / EMG features predict the clinical response of individual epileptic patients to AED.
- AED-induced changes in selected TMS-EEG / EMG features may predict cognitive side effects.
Detailed description
The overarching objective of this study is to develop a combined TMS-EEG/EMG protocol so as to explore the effects of AEDs on cortical excitability and obtain novel electrophysiological biomarkers which could help predict the response of epileptic patients to AEDs, in line with the principles of personalized medicine. In order to achieve the overarching objective, we will perform a Diagnostic Clinical Performance Study, (FDA 2013) with the following specific objectives.
Primary Objective 1: To investigate whether TMS-EEG/EMG biomarkers can predict the response of patients with focal epilepsy to AEDs (Lacosamide \& Brivaracetam).
Secondary Objective 1: Development, testing and validation of novel TMS-EEG/EMG stimulation and multi-level data analysis protocols, incorporating advanced methods of signal analysis, connectivity, complexity, and propagation across the cortical mantle.
Secondary Objective 2: Investigating the sensitivity of TMS-EEG/EMG biomarkers for detecting changes in brain physiology in healthy subjects and patients with focal epilepsy.Secondary Objective 3: Investigating whether TMS-EEG / EMG biomarkers may predict cognitive deficits in patients with focal epilepsy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The study has 2 parts; part I that includes healthy volunteers and part II that includes patients with focal epilepsy. Each healthy volunteer will participate in three sessions every 2 weeks and will receive a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo. Patients in part II will receive either Lacosamide, 300 mg p.o. or Brivaracetam, 100 mg p.o. All participants will perform a test using the tested software that combines a Transcranial Magnetic Stimulation with EEG/EMG
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | Other | Device: Software EstimLTEach healthy volunteer during Part I of the study will receive every 2 weeks a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo. All healthy volunteers will perform tests using the new software that combines Transcranial Magnetic Stimulation Combined With EEG/EMG, |
| Patients with focal epilepsy | Other | Device: Software EstimLTPatients during Part II, will receive the treatment according to the treating physician's discretion, regardless of the protocol, either with Lacosamide, 300 mg p.o. or Brivaracetam, 100 mg p.o. All patients will perform tests using the new software that combines Transcranial Magnetic Stimulation Combined With EEG/EMG, |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Adult volunteers aged 18-65 years
- Able to provide informed consent
- Meet the criteria of the attached TMS safety questionnaire (Rossi et al, 2011). It is clarified that: a) criterion 1 does not apply to the group of patients and b) a positive answer to criteria 5, 6, 8, 9 \& 10 excludes inclusion in the study while the other answers are evaluated by the investigator.
- Adult patients, 18-65 years of age, suffering from focal epilepsy, as evidenced by clinical and EEG features.
- All patients continue suffering from seizures despite treatment with 1-2 concomitant AEDs (with vagal nerve stimulation counting as an AED). In order to be eligible, patients should be suffering from simple partial seizures (SPS) and a motor component or complex partial seizures (CPS) with or without secondary generalization (sGS). Patients should report at least three seizures during the 12 weeks of Historical Baseline.
Key exclusion criteria (15 listed)
- The presence of Central Nervous System "CNS" disorders other than epilepsy on history or examination
- Comorbid psychiatric or medical conditions that may compromise the ability of the individuals to participate in the study
- EEG evidence of generalized epilepsy.
- Uncountable seizures due to clustering.
- Use of centrally acting drugs other than AEDs.
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 |
|---|---|---|
| Software EstimLTHealthy volunteers will receive a single per os dose of Lacosamide (200 mg), Brivaracetam (50 mg) or placebo and then the software will be tested | Device | Healthy volunteers, Patients with focal epilepsy |
Primary outcome
Diagnostic accuracy of TMS Combined With EEG/EMG for predicting response to AEDs
Time frame: 9 months
The Primary Outcome Measure is the diagnostic accuracy (calculated as the number of true positives + true negatives)/(number of true positives + true negatives + false positives + false negatives) of the index test for predicting response to AEDs (defined as reduction of seizure frequency by 50% or more during the maintenance period in comparison to baseline). The primary efficacy endpoint will be assessed in the combined groups of responders (LAC+BRV) and non-responders (LAC+BRV) because the starting hypothesis is that response to AEDs will be associated with alterations in TMS-EEG/EMG biomarkers.
3 secondary outcomes
PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for predicting response to AEDs
Time frame: Through study completion, an average of 2 years
Accuracy, PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for other measures of response to AEDs
Time frame: Through study completion, an average of 2 years
Accuracy of TMS Combined With EEG/EMG for predicting AED-induced side-effects
Time frame: Through study completion, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Software EstimLT in people with Focal Epilepsy, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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 14 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 10 Mar 2023. 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 Greece. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vasilios Kimiskidis, Professor (+30-2310-994667, kimiskid@auth.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of TMS Combined With EEG/EMG for predicting response to AEDs (time frame: 9 months). 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 10 Mar 2023.