Clinical trial NCT06681480: Transcranial Magnetic Stimulation (rTMS) for Refractory Focal Epilepsy
Official title: Transcranial Magnetic Stimulation (rTMS) for the Treatment of Focal Refractory Epilepsy: Neuropsychological and Electrophysiological Evaluation.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Focal Epilepsy
Transcranial Magnetis Stimulation
Keywords: Epilepsy, Focal, Partial, Central Nervous System Diseases, Brain Diseases
Lead sponsor: Comenius University
Sponsor class: OTHER
First posted: 2024-11-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Epilepsy as a brain disease is characterised by enhanced brain excitability. Low frequency repetitive transcranial magnetic stimulation (rTMS) can be an effective treatment for refractory focal epilepsy. Today different ways of stimulation were used, the best protocol of rTMS in refractory focal epilepsy is under evaluation. The aim of our study is neuropsychological and electrophysiological evaluation before and after rTMS sessions, the results of rTMS will be compared with VNS outcome in patients, who undergoes VNS implantation after rTMS.

Detailed description: 1. Background Epilepsy is a chronic disease that causes repetitive seizures. In 60% to 70% of people with epilepsy (PWE) , these seizures start in a small part of the brain (focal epilepsy). Up to 30% of people with epilepsy continue to have seizures despite optimal pharmacological care. Invasive methods - called epilepsy surgery are the choice of treatment for this group of the patients. New non- invasive non- pharmacological methods are on the way.
2. Aim of the study Treatment the people with focal epilepsy with non- invasive transcranial magnetic stimulation (rTMS) to the region that causes the epilepsy. A part of the patients will after that be treated with invasive VNS implantation. The aim is to evaluate neuropsychological and electrophysiological out come in non- invasive arm and in combined arm (VNS after rTMS).
3. Inclusion criteria The patients with neocortical focal epilepsy older than 18 years, not controlled with antiseizure drugs, with confirmed refractory epilepsy.
4. Study methodology The seizure frequency will be controlled with seizure diaries, patients will be evaluated in tertiary epilepsy centre. The patients will be on stable dose of drugs 4 week before and at least 8 weeks after last TMS session. They will be evaluated by battery of neuropsychological tests (cognition, emotions, personality) and electrophysiological methods ( QEEG, SEP n. medianus) before rTMS sessions and after rTMS session and a month later. A part of the patient, who will continue to VNS implantation will be evaluated before VNS implantation and 6 month later again.

   The magnetic pulses will be delivered in a active session or in a placebo session ( sham). The investigators will not tell in which order they deliver the treatments.
5. What are the possible benefits and risks of participating? The investigators believe, that the patients will have fewer seizures in the weeks following the active treatment and that the improvement could be detected in neuropsychological evaluations and in electrophysiology. It is not known, if the results of rTMS could predict the response of the patients to VNS stimulation.

Eligibility criteria: Inclusion Criteria:

- fully characterized refractory focal neocortical epilepsy (i.e. the epileptogenic zone is well defined) on a stable drug regimen for at least one month, able to complete a seizure dairy either by the patient or by a significant other

Exclusion Criteria:

- Metal in the head including deep brain stimulators, aneurysmal clips, ventricular shunts, cochlear implants, ossicular reconstruction of the middle ear, VNS implants pacemaker, implantable cardioverter-defibrillator (ICD) psychogenic non-epileptic seizures and other non-epileptic spells

Primary outcomes:
measure: Seizure frequency and severity
timeFrame: 1 hour
Secondary outcomes:
measure: QOLIE-31-P measurement of different neuropsychological aspects of epilepsy
timeFrame: 20 min
measure: Electrophysiological evaluation with quantitative EEG
timeFrame: 30 min
measure: Comparison the data in the group of the patients
timeFrame: 1 hour
measure: Drop out rate and adverse event profile
timeFrame: 1 hour
measure: LSSS- measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: PHQ-9 measurement of different neuropsychological aspects of epilepsy
timeFrame: 5 min
measure: GAD-7 measurement of different neuropsychological aspects of epilepsy
timeFrame: 5 min
measure: ROCFT measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: STROOP measurement of different neuropsychological aspects of epilepsy
timeFrame: 15 min
measure: TMT AB measurement of different neuropsychological aspects of epilepsy
timeFrame: 5 min
measure: DST measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: AVLT measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: MoCA measurement of different neuropsychological aspects of epilepsy
timeFrame: 20 min
measure: SDMT measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: StT measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: WCST measurement of different neuropsychological aspects of epilepsy
timeFrame: 10 min
measure: Electrophysiological evaluation with quantitative SEP
timeFrame: 1 hour
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: 2nd Department of Neurology, Faculty of Medicine COMENIUS UNIVERSITY BRATISLAVA
state: Slovak Republic
Study officials:
References:
citation: Sun W, Mao W, Meng X, Wang D, Qiao L, Tao W, Li L, Jia X, Han C, Fu M, Tong X, Wu X, Wang Y. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia. 2012 Oct;53(10):1782-9. doi: 10.1111/j.1528-1167.2012.03626.x. Epub 2012 Sep 5.
citation: Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006 Oct;60(4):447-55. doi: 10.1002/ana.20950.
citation: Pereira LS, Muller VT, da Mota Gomes M, Rotenberg A, Fregni F. Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review. Epilepsy Behav. 2016 Apr;57(Pt A):167-176. doi: 10.1016/j.yebeh.2016.01.015. Epub 2016 Mar 10.
citation: Seynaeve L, Devroye A, Dupont P, Van Paesschen W. Randomized crossover sham-controlled clinical trial of targeted low-frequency transcranial magnetic stimulation comparing a figure-8 and a round coil to treat refractory neocortical epilepsy. Epilepsia. 2016 Jan;57(1):141-50. doi: 10.1111/epi.13247. Epub 2015 Dec 8.
citation: Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Lagana A, Inghilleri M, Giallonardo AT, Berardelli A, Pacifici L, Ferreri F, Tombini M, Gilio F, Quarato P, Conte A, Manganotti P, Bongiovanni LG, Monaco F, Ferrante D, Rossini PM. Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Epilepsia. 2007 Feb;48(2):366-74. doi: 10.1111/j.1528-1167.2006.00938.x.