Clinical trial NCT00079781: RNS® System Feasibility Study
Official title: RNS® System Feasibility Clinical Investigation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Keywords: Responsive Stimulation
Brain Stimulator
Epilepsy
Seizures
Lead sponsor: NeuroPace
Sponsor class: INDUSTRY
First posted: 2004-03-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The RNS® System is intended to treat patients with medically refractory (hard to treat) epilepsy. The RNS® System Feasibility study is designed to demonstrate safety and evidence of effectiveness of the RNS® System to support the commencement of a pivotal clinical investigation.

Detailed description: NeuroPace, Inc. is sponsoring an investigational device feasibility study of the RNS® System, the first closed loop responsive brain stimulator designed to treat medically refractory epilepsy. The RNS® System Feasibility study is a multi-center investigation being conducted at 12 epilepsy centers through the United States. The first 4 subjects at each site are entered into an open label protocol, and subsequent subjects at that site are entered into a randomized, double-blinded, sham-stimulation controlled protocol. The study is designed to demonstrate safety and evidence of effectiveness of the RNS® System to support commencement of a pivotal clinical investigation.

The RNS® Neurostimulator (a pacemaker-like device) and NeuroPace® Leads (tiny wires with electrodes) are implanted in the head. The Neurostimulator is a battery powered, microprocessor controlled device that detects and stores records of electrographic patterns (such as epileptiform, or seizure-like, activity) from the Leads within the brain. When the device detects an electrographic pattern, it responds by sending electrical stimulation through the Leads to a small part of the patient's brain to interrupt the electrographic pattern. This type of treatment is called responsive stimulation, but it is not yet known if it will work for the treatment of epilepsy. Direct brain stimulation therapy has already received approval in the United States, Europe, Canada, and Australia for the treatment of Essential Tremor and Parkinson's disease. Direct brain stimulation is not approved for the treatment of epilepsy.

Subjects participating in the RNS® System Feasibility study are required to have successfully completed the non-significant risk Prospective Seizure Frequency (PSF) study, which gathers baseline(pre-implant) seizure frequency data. Subjects must also met the inclusion criteria, including localization of epileptogenic region(s), prior to enrolling in the study. Throughout the entire study, subjects or their caregivers must keep a seizure diary. Seizure frequency, seizure severity, and antiepileptic medications, as well as physical and emotional health will be monitored and recorded throughout the study. Antiepileptic medications should continue to remain stable until 5 months post-implant.

Following enrollment, and prior to RNS® System implant, subjects undergo a neuropsychological evaluation. During the implant procedure, the RNS® Neurostimulator is cranially implanted and connected to one or two NeuroPace® Leads implanted in the brain. The investigational team determines the placement of the Leads based on prior localization of the epileptogenic region, according to standard localization procedures.

The Evaluation Period begins once the subject is implanted with the RNS® System and continues through the 4th month. Detection of epileptiform activity is enabled for all subjects within the first post-operative month. Responsive stimulation is enabled and optimized for subjects enrolled in the open label protocol or randomized to the Treatment group. Subjects randomized to the Sham group undergo simulated stimulation programming in order to maintain the treatment blind. Randomized subjects will not know whether responsive stimulation is being delivered or not.

At the beginning of the 5th month, subjects transition into the Follow up Period during which all subjects may receive responsive stimulation and antiepileptic medications may be adjusted as medically required. Subjects will be followed for 2 years post-implant. Throughout study participation, both effectiveness and safety data will be monitored continuously, and reviewed and documented by the study investigator at study appointments scheduled every 1-3 months.

Eligibility criteria: Inclusion Criteria:

1. Subject has simple partial seizures (motor or sensory) or complex partial seizures (with motor manifestations) with or without secondarily generalized seizures
2. Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the investigator, by the subject or caregiver
3. Subject has seizures that are severe enough to cause injuries or significantly impair functional ability in domains including employment, psychosocial, education and mobility
4. Subject failed treatment with a minimum of two antiseizure medications (used in appropriate doses) with adequate monitoring of compliance and the effects of treatment
5. Subject has remained on the same antiseizure medication(s) over the preceding three (3) months (independent of dose and other than acute, intermittent use of benzodiazepines)
6. Subject has a minimum of four (4) or more countable seizures every month over the last three (3) months, as reported from the NeuroPace sponsored Prospective Seizure Frequency Clinical Investigation
7. Subject is ≥ 18 years old and ≤ 65 years old
8. Subject has undergone diagnostic testing that has established the epileptiform activity onset region(s) as part of his/her standard care to determine candidacy for epilepsy surgery
9. Subject is male, or if female is using a reliable method of contraception (hormonal, barrier method, surgical or abstention), or is at least two years postmenopause
10. Subject or legal guardian is able to provide appropriate consent to participate
11. Subject can be reasonably expected to maintain a seizure diary alone or with the assistance of a competent individual
12. Subject is able to complete regular office visits and telephone appointments per the protocol requirements
13. Subject is willing to be implanted with the RNS® System as a treatment for his/her seizures
14. Subject is able to tolerate a neurosurgical procedure
15. Subject is considered a good candidate to be implanted with an RNS® System

Note: 1 month = 28 days

Exclusion Criteria:

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. In the opinion of the investigator, the subject has a clinically significant or unstable medical condition or a progressive central nervous system disease
5. Subject has been diagnosed with active psychosis, severe depression or suicidal ideation in the preceding year
6. Subject is pregnant or planning on becoming pregnant in the next year
7. Subject is on the ketogenic diet
8. Subject was enrolled in a therapeutic investigational drug or device study in the preceding year
9. Subject has an implanted Vagus Nerve Stimulator (VNS)
10. Subject has had therapeutic surgery to treat epilepsy in the preceding year
11. Subject is implanted with an electronic medical device that delivers electrical energy to the head or body
12. Subject is on chronic anticoagulants or, in the opinion of the investigator, subject is an unsuitable candidate for cranial surgery for any other reason
13. Subject had a cranial neurosurgical procedure in the previous month
14. Subject requires repeat MRIs
15. Subject's seizure onset zone(s) is/are located below the level of the subthalamic nucleus or, in the opinion of the investigator, the necessary lead placement would present too high a risk

Note: Subjects with an inactive VNS could be enrolled so long as the VNS was explanted prior to or at the same time as the RNS® System implant. Subjects who had had epilepsy surgery (resective, corpus callosotomy or ablation) greater than one year ago were still eligible.

Primary outcomes:
measure: Acute SAE Rate
timeFrame: Initial implant through 1 month post-implant
measure: Short-term Chronic SAE Rate
timeFrame: Initial implant through 3 months post-implant
measure: Responder Rate
timeFrame: Pre-implant baseline through 4 months post-implant
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center / Epilepsy Center
state: Illinois
city: New Orleans
country: United States
facility: Louisiana State University Epilepsy Center of Excellence
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Columbia University / Columbia Presbyterian Medical Center
state: New York
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Columbia University / Columbia Presbyterian Medical Center
name: Robert Goodman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Hospital
name: Gregory Barkley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Greg Bergey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Louisiana State University Epilepsy Center of Excellence
name: Bruce Fisch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Robert Wharen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Richard Marsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Richard Zimmerman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University
name: Anthony Murro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center / Epilepsy Center
name: Donna Bergen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center / Epilepsy Center
name: Michael Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swedish Medical Center
name: Ryder Gwinn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Douglas Labar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Robert Duckrow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barkley GL, Smith B, Bergey G, Worrell G, Chabolla D, Drazkowski J, Labar D, Duckrow R, Murro A, Smith M, Gwinn R, Fisch B, Hirsch L, and Morrell M. Safety and Preliminary Efficacy of the RNS Responsive Neurostimulator for the Treatment of Intractable Epilepsy in Adults. Epilepsia 2006; 47(S4):5.