Clinical trial NCT04158531: REC2Stim as a Treatment for Refractory Epilepsy in the Primary Sensorimotor Cortex.
Official title: Rational Extra-eloquent Closed-loop Cortical Stimulation (REC2Stim) as a Treatment for Refractory Epilepsy in the Primary Sensorimotor Cortex.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Epileptic Seizure
Epilepsy Intractable
Motor Seizure
Keywords: cortical electrical stimulation
seizure detection
network stimulation
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2019-11-08
Enrollment: 10
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is an early feasibility study in which the effect and safety of cortical network stimulation in patients with central lobe epilepsy is investigated.
Primary purpose: TREATMENT

Brief summary: People with central lobe epilepsy (CLE), with seizures arising from the primary sensorimotor cortex, typically show a high rate of convulsive seizures that do not respond to anti-epileptic drugs, but have a large impact on quality of life. They often seek surgical relief, but since the area contains the body's indispensable sensorimotor representation, CLE surgery will lead to permanent functional deficits. Cortical stimulation case studies in CLE have shown seizure frequency reduction of more than 90%, but in our experience, stimuli in the central lobe can hardly be applied without interfering with motor function.

The investigators propose cortical electrical stimulation therapy of a conceptually novel type. The investigators systematically determine individual stimulation settings, stimulation site and a seizure detection algorithm. In REC2Stim (Rational Extra-eloquent Closed-loop Cortical Stimulation), at the start of a seizure, a train of electric pulses is delivered to a nearby extra-eloquent area connected with the epileptogenic area within the sensorimotor cortex. Success will constitute a therapeutic modality for pharmaco-resistant patients with an epileptic focus in eloquent areas.

Detailed description: The investigators will include ten patients with CLE, aged 16 years and older, in whom pre-surgical chronic intracranial EEG monitoring has revealed a seizure onset in the primary sensorimotor cortex. Patients should have on average at least two seizures per day.

Clinical intracranial EEG monitoring (normally 7-10 days) will be extended with two extra monitoring days, for systematic testing of different stimulation settings and their effect on interictal epileptiform EEG activity (as a surrogate marker for ictal epileptiform activity), from which site and parameters for chronic stimulation will be determined.

Upon removal of the clinically implanted electrodes, a neurostimulator with sensing capabilities, Activa PC+S, will be implanted and attached to two subdural leads with electrodes covering the predefined stimulation site and the eloquent epileptogenic area.

During a data collection phase, stimulation-free data will then be collected to train the seizure detection algorithm up to at least 50% sensitivity.

Finally, the REC2Stim phase will be started, in which cortical stimulation is applied when seizure activity is detected. Study participation is one year. When REC2Stim turns out effective in month 10 and 11 after implantation of the neurostimulator, 2 weeks of sham stimulation will follow in month 12.

Eligibility criteria: Inclusion Criteria:

* potential central lobe epilepsy
* on average 2 or more seizures per day or ongoing Epilepsia Partialis Continua (EPC)
* mentally and physically capable of giving informed consent
* minimally 3 anti-epileptic drugs been admitted without effect on seizure frequency (refractory epilepsy)

Exclusion Criteria:

* coagulopathy, including use of anticoagulant or antiplatelet agents
* known allergy to the materials of the implant
* progressive neurological or systemic disease
* contra-indications to the presence of a chronically implanted device, such as the need for repeated MRI, or concurrent infections
* any brain lesion that would place the patient at an elevated risk for bleeding
* any progressive brain disease, e.g. Rasmussen's encephalitis or glioma
* presence of any active implanted metallic device, such as cardiac pace-maker, vagal nerve or deep brain stimulator, cochlear implants, spinal cord stimulator or metallic parts from non-medical origin
* presence of aneurysm clips
* seizure onset zone (SOZ) outside eloquent cortex

Primary outcomes:
measure: seizure frequency - diary recorded in an app (MedApp)
timeFrame: study start until 1 year after implantation of last patient
measure: seizure severity - diary recorded in an app (MedApp)
timeFrame: study start until 1 year after implantation of last patient
Secondary outcomes:
measure: Motoric functioning - muscle strength as part of neurological examination
timeFrame: study start until 1 year after implantation of last patient
measure: Motoric functioning - coordination as part of neurological examination
timeFrame: study start until 1 year after implantation of last patient
measure: Motoric functioning - sensibility as part of neurological examination
timeFrame: study start until 1 year after implantation of last patient
measure: Motoric functioning - reflexes as part of neurological examination
timeFrame: study start until 1 year after implantation of last patient
measure: Simple functional abilities - nine hole peg test
timeFrame: study start until 1 year after implantation of last patient
measure: Complex functional abilities - Action Research Arm Test (ARAT)
timeFrame: study start until 1 year after implantation of last patient
measure: Quality of life questionnaire
timeFrame: study start until 1 year after implantation of last patient
measure: Participation abilities - Utrecht´s Scale for Evaluation of Rehabilitation (USER)- Participation questionnaire
timeFrame: study start until 1 year after implantation of last patient
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Frans Leijten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: