RNS® System Pivotal Study
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: RNS® System implantation; RNS® System responsive stimulation
Intervention description: Using standard neurosurgical techniques the surgical team implants the RNS® System, which includes the RNS® Neurostimulator and intracranial NeuroPace® Leads. Up to 4 Leads (Cortical Strips and/or Depth Leads) are placed in or near the epileptogenic focus/foci. The Neurostimulator is placed in the skull and connected to up to 2 Leads. At first the Neurostimulator is programmed to record brain activity (electrographic patterns). The neurologist or neurosurgeon reviews the recorded electrographic patterns and identifies abnormal (epileptiform, or seizure-like) activity. The Neurostimulator is then programmed to detect the abnormal activity.; The RNS® System is programmed to provide responsive stimulation (stimulation is ON or enabled). Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal (epileptiform, or seizure-like) activity, the Neurostimulator provides brief pulses of electrical stimulation through the Leads to interrupt those patterns. The typical patient is treated with a cumulative total of 5 minutes of stimulation a day.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Responsive Stimulation; Brain Stimulator; Epilepsy; Seizures

Summary:

      The RNS® System Pivotal study is designed to assess safety and demonstrate that the RNS®
      System is effective as an adjunctive (add-on) therapy in reducing the frequency of seizures
      in individuals 18 years of age or older with partial onset seizures from no more than two
      foci (two areas of the brain) that are refractory (drug-resistant or hard-to-treat) to two or
      more antiepileptic medications. Patients continue to receive their epilepsy medications while
      participating in the study.
    

Eligibility criteria:

        Inclusion Criteria for enrollment:

          1. Subject has 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 ability.

          2. Subject's seizures are distinct, stereotypical events that can be reliably counted.

          3. Subject failed treatment with a minimum of 2 anti-seizure medications.

          4. Subject has remained on the same antiepileptic medication(s) over the 3 most recent
             consecutive months (other than acute, intermittent use of benzodiazepines). Subjects
             on the ketogenic diet are permitted if the diet has been stable for the preceding 3
             months.

          5. Subject reports having an average of 3 or more disabling motor simple partial
             seizures, complex partial seizures and/or secondarily generalized seizures per month
             over the 3 most recent consecutive months, with no month with less than 2 seizures.

          6. Subject is between the ages of 18 and 70 years.

          7. Subject has undergone diagnostic testing that has identified no more than 2
             epileptogenic regions.

          8. Subject is male or a female of childbearing potential using a reliable method of
             contraception or is at least two years post-menopause.

          9. Subject or legal guardian is able to provide appropriate consent to participate.

         10. Subject can be reasonably expected to maintain a seizure diary alone or with the
             assistance of a competent individual.

         11. Subject is able to complete regular office and telephone appointments per the protocol
             requirements.

         12. Subject is willing to be implanted with the RNS® System as a treatment for his/her
             seizures.

         13. Subject is able to tolerate a neurosurgical procedure.

         14. Subject is considered a good candidate to be implanted with the RNS® System.

        Note: A subject is still eligible to participate if antiepileptic medication(s) were
        temporarily discontinued for the purposes of diagnostic or medical procedures during the
        preceding 3 months.

        Exclusion Criteria for enrollment:

          1. Subject has been diagnosed with psychogenic or non-epileptic seizures in the preceding
             year

          2. Subject has been diagnosed with primarily generalized seizures.

          3. Subject has experienced unprovoked status epilepticus in the preceding year.

          4. Subject has a clinically significant or unstable medical condition (including alcohol
             and/or drug abuse) or a progressive central nervous system disease.

          5. Subject is taking chronic anticoagulants.

          6. Subject has been diagnosed with active psychosis, major depression or suicidal
             ideation in the preceding year. Subjects with post-ictal psychiatric symptoms need not
             be excluded.

          7. Subject is pregnant or planning on becoming pregnant in the next 2 years.

          8. Subject is enrolled in a therapeutic investigational drug or device trial.

          9. Subject has an implanted Vagus Nerve Stimulator (VNS) or is unwilling to have the VNS
             explanted. (VNS therapy must have been discontinued for at least 3 months prior to
             enrollment.)

         10. Subject has had therapeutic surgery to treat epilepsy in the preceding 6 months.

         11. Subject has had a cranial neurosurgical procedure (including endovascular procedures)
             other than an epilepsy surgery involving the skull or brain in the previous month.

         12. Subject is implanted with an electronic medical device that delivers electrical energy
             to the head.

         13. Subject is an unsuitable candidate for neurosurgery.

         14. Subject requires repeat MRIs in which the head is exposed to the radio frequency
             field.

         15. Subject's epileptogenic region(s) is/are located caudal to the level of the thalamus.

         16. Implantation of the RNS® Neurostimulator and Lead(s) would present unacceptable risk.