TMS Combined With EEG/EMG as a Biomarker Predicting Antiepileptic Drug Response

NCT05278221 | Unknown

• 1 other identifier: BIOEPI
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Ιn the present study (BIOEPI), the following three hypotheses will be investigated:

1. 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. 2.AED-induced changes in selected TMS-EEG / EMG features predict the clinical response of individual epileptic patients to AED.
3. 3.AED-induced changes in selected TMS-EEG / EMG features may predict cognitive side effects.

Conditions

Focal Epilepsy

Keywords

epilepsy, medical device

Outcome Measures

Primary Outcomes (1)

• 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.

  9 months

Secondary Outcomes (3)

• PPV, NPV, LR+ & LR- of TMS Combined With EEG/EMG for predicting response to AEDs

  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

  Through study completion, an average of 2 years

• Accuracy of TMS Combined With EEG/EMG for predicting AED-induced side-effects

  Through study completion, an average of 2 years

Study Arms (2)

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,

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,

Device: Software EstimLT

Interventions

Software EstimLT DEVICE

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

Healthy volunteers; Patients with focal epilepsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General criteria:
• Adult volunteers aged 18-65 years
• Able to provide informed consent
• Specific criteria:
• The specific criteria per group of study participants are as follows:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

Prof. Vasilios Kimiskidis

Thessaloniki, Thessaloniki, 546 36, Greece

RECRUITING

MeSH Terms

Conditions

Epilepsies, Partial; Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Vasilios Kimiskidis, Professor

CONTACT

+30-2310-994667; kimiskid@auth.gr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The evaluator of the outcomes will be blinded
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: March 14, 2022
• Study Start: August 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: March 31, 2024
• Last Updated: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)