REC2Stim as a Treatment for Refractory Epilepsy in the Primary Sensorimotor Cortex. (REC2Stim)

Rational Extra-eloquent Closed-loop Cortical Stimulation (REC2Stim) as a Treatment for Refractory Epilepsy in the Primary Sensorimotor Cortex.

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.

Study Overview

• Status: Unknown
• Conditions: Epilepsy Intractable; Epileptic Seizure; Motor Seizure
• Intervention / Treatment: Device: ECoG sensing and stimulation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frans Leijten, MD, PhD; Phone Number: +31 88 75 579 83; Email: F.S.S.leijten@umcutrecht.nl
• Study Contact Backup: Name: Nick Ramsey, PhD; Phone Number: +31 88 755 6862; Email: N.F.Ramsey@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • University Medical Center Utrecht
    • Contact: Frans Leijten, MD, PhD; Phone Number: +31 88 75 579 83; Email: F.S.S.leijten@umcutrecht.nl
    • Contact: Nick Ramsey, PhD; Phone Number: +31 88 755 6862; Email: N.F.Ramsey@umcutrecht.nl
    • Principal Investigator: Frans Leijten, MD, PhD
    • Sub-Investigator: Nick Ramsey, PhD
    • Sub-Investigator: Erik Aarnoutse, PhD
    • Sub-Investigator: Geertjan Huiskamp, PhD
    • Sub-Investigator: Dorien van Blooijs, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REC2Stim; Use electrocorticography (ECoG)-based seizure detection and cortical network stimulation upon seizure onset detection.	Device: ECoG sensing and stimulation; Implant electrodes and a sensing+stimulation device, and use this for suppression of seizure activity; Other Names: Activa PC+S

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
seizure frequency - diary recorded in an app (MedApp)	the number of seizures per day	study start until 1 year after implantation of last patient
seizure severity - diary recorded in an app (MedApp)	the severity of the seizures, experienced by the patient. A scale of intensity from 0-10 (low - high severity) can be selected. Also the seizure type can be selected.	study start until 1 year after implantation of last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motoric functioning - muscle strength as part of neurological examination	The investigators perform neurological examination during each outpatient clinic visit. We test muscle strength and scale that with the Medical Research Council Scale (MRC) (0-5: no contraction - normal strength).	study start until 1 year after implantation of last patient
Motoric functioning - coordination as part of neurological examination	The investigators perform neurological examination during each outpatient clinic visit. Coordination is rated as normal or abnormal.	study start until 1 year after implantation of last patient
Motoric functioning - sensibility as part of neurological examination	The investigators perform neurological examination during each outpatient clinic visit. Sensibility is rated as normal or abnormal.	study start until 1 year after implantation of last patient
Motoric functioning - reflexes as part of neurological examination	The investigators perform neurological examination during each outpatient clinic visit. Reflexes are rated as normal or abnormal.	study start until 1 year after implantation of last patient
Simple functional abilities - nine hole peg test	The investigators use the nine-hole peg test before implantation and 1 year after implantation. The investigators record the time it takes to place 9 sticks in openings and back on the plate again.	study start until 1 year after implantation of last patient
Complex functional abilities - Action Research Arm Test (ARAT)	The investigators use the ARAT before implantation and 1 year after implantation. Scale ranges from 0-57 points (bad - normal performance).	study start until 1 year after implantation of last patient
Quality of life questionnaire	The patient fills in the Assessment of Quality of Life (AQoL-8D). Scale ranges from 35-175 (high - low quality of life).	study start until 1 year after implantation of last patient
Participation abilities - Utrecht´s Scale for Evaluation of Rehabilitation (USER)- Participation questionnaire	The patient fills in the USER-participation questionnaire. Score ranges from 0-500 (low - good participation)	study start until 1 year after implantation of last patient

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Frans Leijten, MD, PhD, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: seizure detection; cortical electrical stimulation; network stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Drug Resistant Epilepsy
• Other Study ID Numbers: NL66795.041.18; NEF17-07 (Other Grant/Funding Number: Dutch Epilepsy Foundation); METC19-336 (Registry Identifier: MREC Utrecht)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: selected datasets will be available through a public repository after publication of results
• IPD Sharing Time Frame: From January 2023, no end date

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No