Deep Brain Stimulation bij epilepsie

Een mogelijk veel belovende therapie bij bepaalde geselecteerde vormen van epilepsie is Deep Brain Stimulation (DBS). Hierbij vindt stimulatie van de diepe hersenkernen plaats. In de Verenigde Staten wordt momenteel onderzoek gedaan naar het effect van Deep Brain Stimulatie bij epilepsie middels het neuropace systeem. Dit is het eerste zogenaamde ‘closed loop system’ voor deep brain stimulation / diepe hersenstimulatie. Het is een soort ‘on demand’ systeem dat een reeks elektrische pulsen geeft zodra door een continue EEG meting epileptiforme signalen gemeten worden.

Het boven beschrevene verkeert nog in het onderzoek stadium en is dus geen geaccepteerde door de verzekeraars vergoede therapie.

Neuropace

Overview
The RNS™ System, designed for the treatment of medically refractory partial epilepsy, includes implantable and external products.

Implantable components include the RNS neurostimulator as well as depth leads and cortical strip leads. The RNS neurostimulator is a programmable, battery powered, microprocessor-controlled device that delivers a short train of electrical pulses to the brain through implanted leads. In treating epilepsy, the RNS neurostimulator is designed to detect abnormal electrical activity in the brain and respond by delivering electrical stimulation to normalize brain activity before the patient experiences seizure symptoms. The neurostimulator is implanted in the cranium and connected to one or two leads that are implanted near the patient’s seizure focus.

External products include the programmer, a laptop computer with proprietary software that has a wand and telemetry interface enabling communication with an implanted RNS neurostimulator. Physicians use the programmer to non-invasively program the detection and stimulation parameters of an implanted device. Additional features of the programmer include the ability to view the patient’s electrocorticographic (ECoG) activity real-time and the ability to upload the patient’s ECoGs that have been stored in the RNS neurostimulator.

Caution: The RNS™ System is an Investigational device. Limited by United States law to investigational use.

Clinical Trials

Overview
Epilepsy is a chronic neurological condition affecting over 2.5 million Americans of all ages. Despite treatment with antiepileptic medications, approximately 40-50% of people with epilepsy continue to experience seizures or have intolerable medication side effects. Epilepsy surgery may be an option for some individuals with refractory (hard to treat) epilepsy. However, many people cannot have surgery because it would be too risky and/or is unlikely to be helpful. Consequently, new therapies for epilepsy are needed. Brain devices to treat epilepsy are currently being studied and may offer hope to those persons with epilepsy who are not adequately treated by antiepileptic medication and are not candidates for epilepsy surgery.

What is the purpose of the RNS™ System Pivotal Clinical Investigation?
NeuroPace, Inc. is sponsoring an investigational device study of the RNS System, the company’s responsive brain stimulation system for treating refractory epilepsy. The RNS System Pivotal Clinical Investigation is a randomized, double-blind, sham stimulation controlled investigation being conducted at approximately 28 sites throughout the United States. The purpose of the RNS System Pivotal Clinical Investigation is to assess the safety and to demonstrate that the RNS System is effective as an add-on (adjunctive) therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures (those that start from one or two areas of the brain) that are refractory (resistant or hard to treat) to two or more antiepileptic medications. Participants in the trial will continue to receive their epilepsy medications.

What is the RNS System?
The RNS is designed to detect abnormal electrical activity in the brain and to deliver small amounts of electrical stimulation to suppress seizures before there are any seizure symptoms. The RNS is placed within the skull and underneath the scalp by a surgeon. The RNS is then connected to one or two wires containing electrodes that are placed within the brain or rest on the brain surface in the area of the seizure focus (where seizures start). The RNS is designed to continuously monitor brain electrical activity from the electrodes and, after identifying the “signature” of a seizure’s onset, deliver brief and mild electrical stimulation with the intention of suppressing the seizure. This type of treatment is called responsive stimulation, but it is not yet known if it will work for the treatment of epilepsy.

A modified laptop computer known as a programmer communicates with the RNS via a hand-held wand. The programmer collects information from the RNS about brain electrical activity and is used to program the RNS to make detections and deliver responsive stimulation.

How Long Does the Clinical Trial Last and How is the Study Designed?
Study participation is expected to last approximately two to three years depending on when the eligibility criteria is met for implantation of the RNS.

After enrolling in the study, participants first complete the baseline period, which lasts a minimum of three months and a maximum of 15 months. During this part of the study, participants will be given a seizure diary to keep track of their seizures on a daily basis. The doctor in charge of the study will review the frequency and severity of seizures during monthly telephone calls or office visits. Study participants must have an average of three seizures for three consecutive months to be eligible for implantation of the RNS.

Once the eligibility criteria have been met, participants will be implanted with the RNS. Study doctors will check on a participant’s physical and emotional health and manage the RNS during regularly scheduled follow-up visits. Participants will continue to keep a daily seizure diary.

The RNS System Pivotal Clinical Investigation is a randomized, double-blind, sham stimulation controlled investigation. The double-blinded portion of the trial begins 28 days after the RNS is implanted and lasts about four months. Half of the participants will be randomly assigned (by chance) to have responsive stimulation turned ON and half will have responsive stimulation turned OFF (sham-stimulation). Participants and one doctor in the trial will not know whether stimulation is being delivered or not. Another doctor will program the RNS. Five months after the RNS has been implanted, when the double-blinded portion of the trial is completed, all participants will be able to have stimulation turned ON.

What Previous Clinical Research has been done with the RNS System?
Previous research has shown that electrical stimulation of the brain can stop seizure activity. Here is an example of the brain’s electrical activity showing the use of electrical stimulation to stop a seizure in someone’s brain (Figure 1)*.

* Bergey, GB, et.al., Implementation of an external responsive neurostimulator system (eRNS) in patients with intractable epilepsy undergoing intracranial seizure monitoring. Epilepsia Vol 43, Suppl 7, 2002

What are the Risks of Participating in the Clinical Trial?
Clinical trials involve risks. There may be side effects or adverse reactions to the device or therapy, or the therapy may make seizures worse. Implant of the RNS requires brain surgery; as with any type of surgery there is risk involved. Any person involved in this study will be given an informed consent form that describes all known risks. As there is limited experience with the RNS System, there may also be other risks that are currently unknown. Prior to participation in a clinical study, it is always important to discuss the clinical trial procedures, risks, and potential benefits of any procedure or operation in more detail with the physician at the clinical trial site.

Who is Eligible to Participate in the Clinical Trial?
Individuals who have been diagnosed with partial onset epilepsy (those that start from one or two areas of the brain) and have an average of three seizures per month that have not been controlled by taking two or more antiepileptic medications may be eligible to participate in this study. For more information about eligibility criteria, see the Inclusion/Exclusion criteria below or contact the closest participating center.

Inclusion/Exclusion Criteria

Inclusion Criteria

1. Disabling motor simple partial seizures, complex partial seizures, and/or secondarily generalized seizures. Disabling refers to seizures that are severe enough to cause injuries, or significantly impair functional abilities in areas such as employment, psychological or social wellbeing, education or mobility.
2. Failed treatment with a minimum of two antiepileptic medications.
3. Experienced an average of three or more disabling motor simple partial seizures, complex partial seizures and/or secondarily generalized seizures every 28 days for three consecutive 28-day periods.
4. Between the ages of 18 and 70 years.
5. No more than two epileptogenic regions in the brain.

Note: Persons implanted with a vagus nerve stimulator (VNS) may be eligible for the RNS trial if the VNS is turned off for a period of time and the person is willing to have the VNS generator explanted (excluding leads) prior to or at the time of the RNS implant.

A list of some of the participating study centers is provided below.

Participating Institutions
The following sites are currently enrolling patients in this study. There may be other study sites that are not listed. You may contact NeuroPace for a complete list.

Caution: The RNS™ System is an Investigational device. Limited by United States law to investigational use.

To learn more about clinical trials, visit:

ClinicalTrials.gov

U.S. Food and Drug Administration