Clinical trial NCT05278221: TMS Combined With EEG/EMG as a Biomarker Predicting Antiepileptic Drug Response
Official title: Development and Optimization of Transcranial Magnetic Stimulation (TMS) Combined With EEG/EMG as a Biomarker Predicting Response to Antiepileptic Drugs
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Focal Epilepsy
Keywords: epilepsy, medical device
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2022-03-14
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: DIAGNOSTIC

Brief 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 antiepileptic drugs (AED) with different mechanisms of action (lacosamide \& brivaracetam) in the Central Nervous System under healthy and pathological conditions (Epilepsy).
2. AED-induced changes in selected TMS-EEG / EMG features predict the clinical response of individual epileptic patients to AED.
3. 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.

Eligibility criteria: Inclusion Criteria:

General criteria:

1. Adult volunteers aged 18-65 years
2. Able to provide informed consent
3. 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:

Patient Group:

1. Adult patients, 18-65 years of age, suffering from focal epilepsy, as evidenced by clinical and EEG features.
2. 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.
3. Patients are required to be Lacosamide and Brivaracetam-naive and, in the latter case, not taking concomitant Levetiracetam.
4. 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.
5. 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

Exclusion Criteria:

The specific criteria per group of study participants are as follows:

Patient Group:

1. The presence of Central Nervous System "CNS" disorders other than epilepsy on history or examination
2. Comorbid psychiatric or medical conditions that may compromise the ability of the individuals to participate in the study
3. EEG evidence of generalized epilepsy.
4. Uncountable seizures due to clustering.
5. Use of centrally acting drugs other than AEDs.
6. Pregnancy or planned pregnancy prior to the index test.

Healthy control group:

1. Presence of medical or psychiatric conditions that may interfere with the procedures.
2. Contraindications to TMS (i.e. pregnancy, presence of heart pacemakers, metal objects etc).
3. History of adverse reactions to pharmacological agents.
4. History of alcohol or nicotine abuse or use of any other centrally acting drug.
5. Participation in another clinical trial in the previous 8 weeks.
6. Pregnancy or planned pregnancy prior to the index test.

Primary outcomes:
measure: Diagnostic accuracy of TMS Combined With EEG/EMG for predicting response to AEDs
timeFrame: 9 months
Secondary outcomes:
measure: PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for predicting response to AEDs
timeFrame: Through study completion, an average of 2 years
measure: Accuracy, PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for other measures of response to AEDs
timeFrame: Through study completion, an average of 2 years
measure: Accuracy of TMS Combined With EEG/EMG for predicting AED-induced side-effects
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Thessaloníki
country: Greece
facility: Prof. Vasilios Kimiskidis
state: Thessaloniki
Study officials:
References: