|- candidate number||19505|
|- NTR Number||NTR4795|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||18-sep-2014|
|- Secondary IDs||NL49901.044.14 P14-21 METC|
|- Public Title||Dubbel puls TMS-EEG bij epilepsie: het evalueren van de therapeutische werkzaamheid|
|- Scientific Title||Paired pulse TMS-EEG in epilepsy: improving the evaluation of therapeutic efficacy|
|- hypothesis||Due to an increased cortical excitability of the brain of epilepsy patients, epileptic seizures can occur. Since, transcranial magnetic stimulation (TMS) provides the opportunity to assess cortical excitability, paired pulse TMS is a candidate technique to evaluate the therapeutic efficacy of anti-epileptic drugs (AEDs) in epilepsy. We expect to measure an increased cortical excitability in drug naïve epilepsy patients prior to AED use, which decreases to normal values in case the patient responds to AEDsm while it remains increased in case the patient does not respond to AEDs. Hopefully, it is thus possible to evaluate the therapeutic efficacy of prescribed AEDs faster and more reliable.|
|- Healt Condition(s) or Problem(s) studied||Epilepsy, Transcranial magnetic stimulation (TMS)|
|- Inclusion criteria||• Diagnosis of epilepsy, either generalized or focal |
• Drug naïve, no prior use of AEDs
• Ability to understand and comply with the instructions for the TMS sessions
|- Exclusion criteria||• Younger than 18 years |
• Contra-indications of TMS (although not absolute): (possibility of) pregnancy, metal objects in brain/skull, cochlear implant, deep brain stimulator, history of spinal cord surgery, drains in the spinal cord or ventricles, use of seizure threshold lowering medication
• Follow-up impossible due to logistical reasons
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-sep-2014|
|- planned closingdate||31-dec-2017|
|- Target number of participants||80|
|- Interventions||TMS (transcranial magnetic stimulation) is a non-invasive, safe, easy, and painless technique to stimulate the brain. In this study TMS is combined with both EMG and EEG.
Prior to the TMS measurements, the motor hot spot and resting motor threshold (rMT) of the abductor digiti polices brevis muscle are determined on both sides. Furthermore, a 64 channel EEG is applied.
Hereafter, 50 pairs of pulses (conditioning pulse followed by test pulse) are given randomly at six different interstimulus intervals (ISIs): 50, 100, 150, 200, 250 and 300 ms. Both pulses are given at an intensity of 120% the rMT.
|- Primary outcome||The main study parameters are the presence and characteristics of the TMS-EMG (MEP) and TMS-EEG (TEP) response.
1) MEP response
• Resting motor threshold (rMT) - Tesla
• Long intracortical inhibition (LICI) - percentage ratio of the mean peak-to-peak amplitude of the response to the second test pulse (TR) and the first conditioning pulse (CR) at each ISI (TR/CR%)
2) TEP response
• Amplitude of peaks - microV
• Latencies of peaks - ms
|- Secondary outcome||Additional signal analysis methods applied on the MEP and TEP. For example, wavelet analysis of early and late TEPs and the spatio-temporal characteristics of the TEP.|
|- Timepoints||All patients will undergo 3 to 4 paired pulse TMS sessions, over a period of one year.
The first TMS session will take place while the patient is still drug naïve, the second session 8 to 12 weeks after starting with AEDs, and the final session 1 year after starting with AEDs. Optionally, an additional fourth TMS session will take place, in case a second AED is prescribed (8-12 weeks after starting the second AED).
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| A.A. Goede, de|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. ir. M.J.A.M. Putten, van|
|- Sponsor/Initiator ||University of Twente|
(Source(s) of Monetary or Material Support)
|Stichting TWIN |
|- Brief summary||Rationale: |
Epilepsy is one of the most common neurological disorders. Due to an increased cortical excitability of the brain of epilepsy patients, epileptic seizures can occur. Once the diagnosis of epilepsy is confirmed, in most patients anti-epileptic drugs (AEDs) are prescribed. These AEDs should reduce the number and/or severity of the epileptic seizures. Because, absence or re-occurrence of seizures after prescribing medication is the only indication to assess whether therapy is successful or not, evaluation of therapeutic efficacy is often time-consuming. Transcranial magnetic stimulation (TMS) in combination with EEG makes it possible to stimulate the brain, while simultaneously assessing cortical excitability. The combination of paired pulse TMS-EEG makes it hopefully possible to evaluate the therapeutic efficacy of prescribed AEDs faster and more reliable.
The primary objective is to evaluate differences in motor evoked potential (MEP) and TMS evoked potential (TEP) to paired pulse TMS between epilepsy patients with a successful response to AEDs and those who do not (refractory patients).
Secondary objectives are:
1) To evaluate differences in MEP and TEP to paired pulse TMS in epilepsy patients with different types of epilepsy or using different types of AEDs
2) To explore (additional) signal analysis techniques for characterising the MEP and TEP to paired pulse TMS
Interventional study at the Clinical Neurophysiology and Neurology departments of the Medisch Spectrum Twente.
40 drug naïve patients with generalized epilepsy and 40 drug naïve patients with focal epilepsy, who are starting with AEDs. Subjects are excluded when they are younger than 18 years, have an (absolute) contra-indication for TMS or when follow-up is impossible for logistical reasons.
All patients will undergo 3 to 4 paired pulse TMS sessions, over a period of one year. The first TMS session will take place while the patient is still drug naïve, the second session 8 to 12 weeks after starting with AEDs, and the final session 1 year after starting with AEDs. Optionally, an additional fourth TMS session will take place, in case a second AED is prescribed (8-12 weeks after starting the second AED). Paired pulse TMS is a non-invasive, safe and painless technique.
Primary study parameters:
Primary study parameters are the characteristics of the MEP (resting motor threshold (rMT) and long intracortical inhibition (LICI)) and TEP (amplitude and latency of peaks).
|- Main changes (audit trail)|
|- RECORD||18-sep-2014 - 10-okt-2014|