Clinical trial NCT03154307: Repeated TMS at Low Frequencies to Reduce Seizure Occurrence
Official title: Repeated TMS at Low Frequencies to Reduce Seizure Occurrence
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Epilepsy
Status Epilepticus
Epilepsia Partialis Continua
Epilepsia Partialis Continua, Refractory (Medically)
Lead sponsor: Baptist Health South Florida
Sponsor class: OTHER
Collaborators: name: U.S. National Science Foundation
name: Florida International University
First posted: 2017-05-16
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Perform non-invasive neuro-navigated repeated Transcranial Magnetic Stimulation (rTMS) at low frequencies (LF) with the intent to reduce the occurrence of seizures over time (long-term protocol). Seizure reduction and improvements in the quality of life in patients with epilepsy will be associated with increased cortical inhibition resulting from the LF-rTMS sessions over time. This procedure using rTMS at low frequencies (LF-rTMS) between 0.5 and 1 Hz is a safe and painless method for noninvasive focal cortical brain stimulation, which will be evaluated in its efficacy at reducing/suppressing seizures. Accordingly, we propose a clinical trial in patients with epilepsy to test whether LF-rTMS can improve seizure suppression. The location of the presumed 3D source in the brain will be stimulated for few minutes (10 to 15 min.). With the same rTMS modality, we will also perform motor threshold mapping in conjunction with its fully integrated and compatible electroencephalography (EEG) module. Up to 100 individuals 18 to 80 years with epilepsy will be enrolled.

In addition, a short-term protocol has been added to test whether LF-rTMS can reduce or suppress status epilepticus in medically refractory participants.

Detailed description: Long term protocol: Perform non-invasive neuro-navigated repeated Transcranial Magnetic Stimulation (rTMS) at low frequencies (LF) with to reduce the occurrence of seizures over time. Seizure reduction and improvements in the quality of life in patients with epilepsy will be associated with increased cortical inhibition resulting from the LF-rTMS sessions over time. This procedure using rTMS at low frequencies (LF-rTMS) between 0.5 and 1 Hz is a safe and painless method for noninvasive focal cortical brain stimulation, which will be evaluated in its efficacy at reducing/suppressing seizures. Accordingly, we propose a clinical trial in patients with epilepsy to test whether LF-rTMS can improve seizure suppression. The location of the presumed 3D source in the brain will be stimulated for few minutes (10 to 15 min.). Using a double-blinded, sham-controlled design, we will enroll up to 100 participants aged 18-80 with focal and generalized retractable epilepsy. Baseline data will include a detailed seizure diary over 4 weeks, psychometric testing/neuropsychology evaluation, and 20-minute EEG recordings. Each patient will then begin treatment with 14 minute sessions of 1 Hz rTMS or sham rTMS, 120%MT, and 800 stimuli on the position of the calculated 3D source using EEG, MRI, and digitized electrode locations. The protocol will be divided in 3 groups (Groups 1, 2 and 3) as follows:

* Groups 1, 2, and 3: LF-rTMS for 2 weeks (5 days per week for total of 10 days).
* Group 1: protocol total duration: 1 year: LF-rTMS 1 session/week for 1 month (4 days), and LF-rTMS 1 session/month for 11 months
* Group 2: protocol total duration: 1 year: LF-rTMS 1 session/month for 12 months
* Group 3 (placebo protocol, total duration: 1 year): LF-rTMS 1 session/week for 1 month (4 days); and LF-rTMS 1session/month.

During each session EEG may be recorded. Also, we will obtain the number, frequency, and duration of seizure events from an ongoing seizure diary. Psychometric testing will be performed at the beginning of study, 3 months, and at the end of the study. Thus, each patient will have rTMS testing, psychometrics, and EEG recordings. With the same rTMS modality, we will also perform motor threshold mapping in conjunction with its fully integrated and compatible electroencephalography (EEG) module.

Short-term protocol: Use LF-rTMS protocol as described but for up to 5 days in 10 participants with medically refractory status epilepticus. During each session EEG will be recorded.

Eligibility criteria: Long-term protocol:

Inclusion Criteria:

* Experience ≥ 3 seizures/month in the month prior to starting study (any type of seizure will count)
* No status epilepticus in the last 12 months
* No change in medication in last 30 days

Exclusion Criteria:

* Presence of implanted electronic devices (e.g., pacemaker, medication pump, brain or vagus nerve stimulator, cochlear implant)
* Presence of intracranial metal (e.g., aneurysm clip)
* Unable to cooperate with non-sedated, navigated TMS testing

Short-term protocol:

Inclusion Criteria:

* Epilepsia partialis continua or status epilepticus
* At least 2 medications failed
* At least 24 hours of acute phase

Exclusion Criteria:

* Presence of implanted electronic devices (e.g., pacemaker, medication pump, brain or vagus nerve stimulator, cochlear implant)
* Presence of intracranial metal (e.g., aneurysm clip)

Primary outcomes:
measure: Average Weekly Seizure Frequency
timeFrame: 6 and 7 weeks post rTMS treatment
measure: Scalp EEG: Number of Interictal Epileptiform Discharges
timeFrame: From start of intervention through 5 days of treatment
measure: Seizure Duration Proxy for Seizure Severity
timeFrame: 6-7-weeks post rTMS treatment
Secondary outcomes:
measure: Interhemispheric EEG Asymmetry Ratio for Alpha Power
timeFrame: 8-weeks Post rTMS Treatment
measure: Scalp EEG Functional Connectivity for Alpha Hz
timeFrame: 8-weeks Post rTMS Treatment
measure: Abductor Pollicis Brevis (APB)-Evoked Response Threshold
timeFrame: 8-weeks Post rTMS treatment
measure: Treatment Response Rate
timeFrame: 8-weeks post rTMS treatment
measure: Intrahemispheric EEG Asymmetry Ratio for Alpha Power
timeFrame: 8-weeks Post rTMS Treatment
Other outcomes:
Locations:
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
Study officials:
affiliation: Baptist Health South Florida
name: Alberto Pinzon, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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