RNS® System Feasibility Study
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.
Procedure: RNS® System implantation
Device: RNS® System responsive stimulation
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||RNS® System Feasibility Clinical Investigation|
- Acute SAE rate [ Time Frame: Initial implant through 1 month post-implant ] [ Designated as safety issue: Yes ]The proportion of implanted subject having a serious adverse event (SAE) for the surgical implant procedure and the following month (28 days).
- Short-term chronic SAE rate [ Time Frame: Initial implant through 3 months post-implant ] [ Designated as safety issue: Yes ]The proportion of implanted subject having a serious adverse event (SAE) for the surgical implant procedure and the following 3 months (84 days).
- Responder rate [ Time Frame: Pre-implant baseline through 4 months post-implant ] [ Designated as safety issue: No ]Proportion of implanted subjects with a 50% or greater reduction in mean seizure frequency during the post-implant Evaluation Period (4 months or 112 days) compared to pre-implant baseline (collected during the Prospective Seizure Frequency study).
|Study Start Date:||January 2004|
|Study Completion Date:||December 2007|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
Active Comparator: Treatment Group (stimulation ON)
Group of subjects that have undergone RNS® System implantation that are randomized to receive RNS® System responsive stimulation (i.e. responsive stimulation enabled or turned ON) during the blinded Evaluation Period. Stimulation is enabled during the first month post-implant and may continue throughout the subject's participation in the study.
Procedure: RNS® System implantation
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.Device: RNS® System responsive stimulation
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.
Sham Comparator: Sham Group (stimulation OFF)
Group of subjects that have undergone RNS® System implantation that are randomized to receive sham-stimulation (i.e. responsive stimulation disabled or turned OFF) during the blinded Evaluation Period. Stimulation is enabled after transition into the Follow-Up Period (5th month post-implant) and may continue for the remainder of the subject's participation in the study.
Procedure: RNS® System implantation
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.
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.
|United States, Arizona|
|Mayo Clinic Scottsdale|
|Phoenix, Arizona, United States, 85054|
|United States, Connecticut|
|Yale University School of Medicine|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Mayo Clinic Jacksonville|
|Jacksonville, Florida, United States, 32224|
|United States, Georgia|
|Medical College of Georgia|
|Augusta, Georgia, United States, 30912|
|United States, Illinois|
|Rush University Medical Center / Epilepsy Center|
|Chicago, Illinois, United States, 60612|
|United States, Louisiana|
|Louisiana State University Epilepsy Center of Excellence|
|New Orleans, Louisiana, United States, 70112|
|United States, Maryland|
|Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, Minnesota|
|Mayo Clinic Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Columbia University / Columbia Presbyterian Medical Center|
|New York, New York, United States, 10032|
|Weill Medical College of Cornell University|
|New York, New York, United States, 10021|
|United States, Washington|
|Swedish Medical Center|
|Seattle, Washington, United States, 98122|
|Principal Investigator:||Robert Goodman, MD||Columbia University / Columbia Presbyterian Medical Center|
|Principal Investigator:||Gregory Barkley, MD||Henry Ford Hospital|
|Principal Investigator:||Greg Bergey, MD||Johns Hopkins University|
|Principal Investigator:||Bruce Fisch, MD||Louisiana State University Epilepsy Center of Excellence|
|Principal Investigator:||Robert Wharen, MD||Mayo Clinic|
|Principal Investigator:||Richard Marsh, MD||Mayo Clinic|
|Principal Investigator:||Richard Zimmerman, MD||Mayo Clinic|
|Principal Investigator:||Anthony Murro, MD||Georgia Regents University|
|Principal Investigator:||Donna Bergen, MD||Rush University Medical Center / Epilepsy Center|
|Principal Investigator:||Michael Smith, MD||Rush University Medical Center / Epilepsy Center|
|Principal Investigator:||Ryder Gwinn, MD||Swedish Medical Center|
|Principal Investigator:||Douglas Labar, MD||Weill Medical College of Cornell University|
|Principal Investigator:||Robert Duckrow, MD||Yale University|