RNS® System Pivotal Study
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.
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, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||RNS® System Pivotal-A 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 5 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).
- Change in seizure frequency [ Time Frame: 3 months pre-implant (Baseline Period) compared to months 3, 4 and 5 post-implant (Blinded Evaluation Period) ] [ Designated as safety issue: No ]Group-by-time interaction term in a generalized estimating equation (GEE), longitudinal regression model, where group refers to therapy allocation (Treatment or Sham), time refers to the study period (Baseline or Blinded Evaluation), and the dependent variable is seizure frequency. The primary effectiveness endpoint was a statistically significant group-by-time interaction term, which would demonstrate a significantly greater reduction in seizure frequency in the Treatment group than the Sham group during the Blinded Evaluation Period compared to the Baseline Period (pre-implant).
|Study Start Date:||December 2005|
|Study Completion Date:||May 2011|
|Primary Completion Date:||October 2009 (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 Stimulation Optimization Period (second 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 places up to four NeuroPace® Leads (Cortical Strips and/or Depth Leads) in or near the epileptogenic focus/foci. The RNS® Neurostimulator is placed in the cranium (skull) and connected to up to 2 NeuroPace® Leads. The Neurostimulator is immediately programmed by the neurologist or neurosurgeon to detect and record brain activity through the Leads. Within the first month following implant the Neurostimulator is programmed to detect electrographic patterns previously identified by the neurologist or neurosurgeon as abnormal (epileptiform, or seizure-like, activity). Responsive stimulation is turned OFF (NOT enabled).Device: RNS® System responsive stimulation
The RNS® Neurostimulator is programmed to provide responsive stimulation (stimulation is turned ON or enabled). Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal, 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 Open Label Period (sixth 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 places up to four NeuroPace® Leads (Cortical Strips and/or Depth Leads) in or near the epileptogenic focus/foci. The RNS® Neurostimulator is placed in the cranium (skull) and connected to up to 2 NeuroPace® Leads. The Neurostimulator is immediately programmed by the neurologist or neurosurgeon to detect and record brain activity through the Leads. Within the first month following implant the Neurostimulator is programmed to detect electrographic patterns previously identified by the neurologist or neurosurgeon as abnormal (epileptiform, or seizure-like, activity). Responsive stimulation is turned OFF (NOT enabled).
NeuroPace, Inc. is sponsoring an investigational device study of the RNS® System, the first closed loop responsive brain stimulator designed to treat refractory epilepsy. The RNS® System Pivotal study is a multi-center, randomized, double-blinded, sham-stimulation controlled investigation being conducted at 32 epilepsy centers throughout the United States. The study is designed to assess safety and demonstrate that the RNS® System is effective in reducing the frequency of medically uncontrolled and disabling partial onset seizures that start from one or two areas of the brain.
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 Pivotal study must met 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.
Upon demonstrating the required seizure frequency and stable antiepileptic medications over 3 consecutive months of the Baseline (pre-implant) Period, subjects will qualify for RNS® System implantation. Antiepileptic medications should continue to remain stable until 6 months post-implant. The surgical procedure will be performed within one month of qualification.
The RNS® Neurostimulator is cranially implanted and connected to one or two NeuroPace® Leads implanted in the brain. The investigational team will determine the placement of the Leads based on prior localization of the epileptogenic region, according to standard localization procedures. Detection of epileptiform activity will be enabled for all subjects during the 1 month Post-Operative Stabilization Period. Subjects will be randomized 1:1 to either the Treatment or Sham group prior to starting the 1 month Stimulation Optimization Period. During this period subjects are seen on a weekly basis by the Treatment Protocol investigator. Responsive stimulation will be enabled and optimized for subjects randomized to the Treatment group. Subjects randomized to the Sham group will be seen for simulated stimulation programming in order to maintain the treatment blind.
The Blinded Evaluation Period is comprised of months 3, 4, and 5 post-implant. Subjects in the Treatment group will receive responsive stimulation and subjects in the Sham group will not. Subjects will not know whether responsive stimulation is being delivered or not. At the end of the 5th month, all subjects' transition into the Open Label Evaluation 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 month for the first year post-implant, then every 3 months.
Show 32 Study Locations
|Principal Investigator:||Gregory Barkley, MD||Johns Hopkins University|
|Principal Investigator:||Michel Berg, MD||University of Rochester|
|Principal Investigator:||Gregory Bergey, MD||Henry Ford Hospital|
|Principal Investigator:||Carl Bazil, MD||Columbia University / Columbia Presbyterian Medical Center|
|Principal Investigator:||Andrew Cole, MD||Massachusetts General Hospital|
|Principal Investigator:||Michael Duchowny, MD||Miami Children's Hospital|
|Principal Investigator:||Robert Duckrow, MD||Yale University|
|Principal Investigator:||Jonathan Edwards, MD||Medical University of South Carolina|
|Principal Investigator:||Stephan Eisenschenk, MD||University of Florida at Gainesville|
|Principal Investigator:||A. James Fessler, MD||University of Rochester|
|Principal Investigator:||Nathan Fountain, MD||University of Virginia|
|Principal Investigator:||Eric Geller, MD||St. Barnabas Medical Center|
|Principal Investigator:||Robert Gross, MD||Emory University|
|Principal Investigator:||Ryder Gwinn, MD||Swedish Medical Center|
|Principal Investigator:||Christianne Heck, MD||University of Southern California|
|Principal Investigator:||Barbara Jobst, MD||Dartmouth-Hitchcock Medical Center|
|Principal Investigator:||David King-Stephens, MD||California Pacific Medical Center|
|Principal Investigator:||James Leiphart, MD||George Washington University|
|Principal Investigator:||W. Richard Marsh, MD||Mayo Clinic|
|Principal Investigator:||Andrew Massey, MD||Via Christi Comprehensive Epilepsy Center|
|Principal Investigator:||Eli Mizrahi, MD||Baylor College of Medicine|
|Principal Investigator:||Dileep Nair, MD||The Cleveland Clinic|
|Principal Investigator:||Cormac O'Donovan, MD||Wake Forest University|
|Principal Investigator:||A. LeBron Paige, MD||University of Alabama at Birmingham|
|Principal Investigator:||Yong Park, MD||Medical College of Georgia / Georgia Health Sciences University|
|Principal Investigator:||Paul Rutecki, MD||University of Wisconsin Hospital and Clinics|
|Principal Investigator:||Vicenta Salanova, MD||Indiana University|
|Principal Investigator:||Christopher Skidmore, MD||Thomas Jefferson University|
|Principal Investigator:||Michael Smith, MD||Rush University Medical Center / Epilepsy Center|
|Principal Investigator:||David Spencer, MD||Oregon Health and Science University|
|Principal Investigator:||Paul Van Ness, MD||University of Texas Southwestern Medical Center|
|Principal Investigator:||Robert Wharen, MD||Mayo Clinic|
|Principal Investigator:||Richard Zimmerman, MD||Mayo Clinic|