RNS® System Epilepsy Post-Approval Study (PAS)

RNS® System Post-Approval Study in Epilepsy

The purpose of the study is to follow patients with partial onset seizures prospectively over 5 years in the real-world environment to gather data on the long-term safety and effectiveness of the RNS System at qualified CECs by qualified neurologists, epileptologists, and neurosurgeons trained on the RNS System.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Device: RNS System

Detailed Description

NeuroPace, Inc. is sponsoring a post-approval study (PAS) of the RNS System device. The RNS System is the first FDA-approved closed loop responsive neurostimulator designed to reduce the frequency of seizures in individuals with partial onset seizures.

The RNS System Epilepsy PAS is a 5 year, non-randomized, open-label, multi-center prospective observational study. Data regarding safety and efficacy are collected at enrollment and periodically throughout the 5-year study.

The study is designed to assess the long-term safety and effectiveness of the RNS System as an adjunctive therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to two or more antiepileptic medications, and currently have frequent and disabling seizures (motor partial seizures, complex partial seizures and/or secondarily generalized seizures).

Data from the RNS System Epilepsy PAS will be used to calculate long-term SAE rates, median percent change in seizure frequency (from pre-implant retrospective data), as well as other safety and effectiveness endpoints.

• Study Type: Observational
• Enrollment (Actual): 345

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham
  • California
    • Irvine, California, United States, 92868
      • University of California, Irvine
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90032
      • University of Southern California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Tampa, Florida, United States
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University Of Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Neuroscience Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Cente
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44193
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University / Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Le Bonheur Children's Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78758
      • Austin Epilepsy Care Center
    • Austin, Texas, United States, 78701
      • Seton Family of Hospital
    • Dallas, Texas, United States, 75390-9036
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States
      • The University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132-5901
      • University of Utah
    • Salt Lake City, Utah, United States, 84157
      • Intermountain Healthcare Research
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Harborview Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Health Services
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to two or more antiepileptic medications, and currently have frequent and disabling seizures.

Description

Inclusion Criteria:

A clinical decision to treat the patient with the RNS System in accordance with its approved indication for use has been made prior to enrollment in the study. For approved indication for use and contraindications, refer to current physician labeling and instructions for use (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

This post-approval study also has the following additional study related inclusion criteria:

• Subject or legal guardian is able to provide appropriate consent to participate
• Subject is able to maintain a seizure diary alone or with the assistance of a competent individual
• Subject is able to attend clinic appointments in accordance with the study schedule

Exclusion Criteria:

Per clinician assessment, treatment with the RNS System is contraindicated based on current RNS System labeling. For approved indication for use and contraindications, refer to current physician labeling and instructions for use (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

This post-approval study has the following additional study related exclusion criteria:

• Subject is participating in a therapeutic investigational drug or device study
• Subject was treated with a VNS within the last three months (90 days)
• Subject is pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Evaluation; A group of subjects with the RNS System implanted who elect to continue to receive RNS System responsive stimulation for the long term.

Device: RNS System; The RNS System provides closed loop responsive brain stimulation. In response to detection of previously identified electrocorticographic activity, the neurostimulator delivers stimulation to the seizure foci by way of the leads to interrupt the activity before the patient experiences clinical seizures. The typical patient is treated with a cumulative total of 5 minutes of stimulation a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAE rate	Calculate annual SAE rates over time in the entire subject population as well as within subpopulations.	Implant through 5 years post-implant
Neurosurgeon experience	Demonstrate there is no difference in safety in 6-week perioperative period based on the experience of NeuroPace qualified and trained implanting physicians.	Implant through 41 days post-implant
Physician experience	Demonstrate there is no difference in safety 1 year post-implant based on experience of NeuroPace qualified and trained treating physicians and Comprehensive Epilepsy Centers.	Implant through 1 year post-implant
Product use - surgical procedures	Present the incidence and number of AEs related to surgical procedures associated with implant, explant, reimplantation, and revision of the neurostimulator and lead(s).
Autopsy	Present data from autopsies obtained from any patient implanted with neurostimulator/leads.
Median percentage reduction in disabling seizure	Demonstrate that the median percentage reduction in disabling seizures over time in the entire subject population is comparable to the median percentage reduction in disabling seizures over time in the LTT study. Characterize the median percentage reduction in disabling seizures over time within subpopulations.	Pre-implant (retrospective data) compared to 30 to 36 months post-implant
Neurostimulator programming	Demonstrate that stimulation programming classes have similar effects on the overall seizure frequency.	Through 5 years post-implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure worsening	Demonstrate that there is not a worsening in disabling seizures over time in the entire subject population. Assess the sustained effect on disabling seizure frequency over time within subpopulations.	6 months post-implant through 36 months post-implant
Neurostimulator programming	Characterize the effects of stimulation programming classes on the overall 5-year rate of SAEs and device-related non-serious AEs.	Implant through 5 years post-implant

Other Outcome Measures

Outcome Measure	Measure Description
Neurostimulator battery longevity	Characterize the clinically observed battery longevity over time and in relation to therapy load in patients treated with the RNS System.

Collaborators and Investigators

• Sponsor: NeuroPace
• Investigators: Study Director: Martha J Morrell, MD, NeuroPace, Inc.

Publications and helpful links

General Publications

• Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, Srinivasan S, Jobst B, Gross RE, Shields DC, Barkley G, Salanova V, Olejniczak P, Cole A, Cash SS, Noe K, Wharen R, Worrell G, Murro AM, Edwards J, Duchowny M, Spencer D, Smith M, Geller E, Gwinn R, Skidmore C, Eisenschenk S, Berg M, Heck C, Van Ness P, Fountain N, Rutecki P, Massey A, O'Donovan C, Labar D, Duckrow RB, Hirsch LJ, Courtney T, Sun FT, Seale CG. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015 Feb 24;84(8):810-7. doi: 10.1212/WNL.0000000000001280. Epub 2015 Jan 23.
• Heck CN, King-Stephens D, Massey AD, Nair DR, Jobst BC, Barkley GL, Salanova V, Cole AJ, Smith MC, Gwinn RP, Skidmore C, Van Ness PC, Bergey GK, Park YD, Miller I, Geller E, Rutecki PA, Zimmerman R, Spencer DC, Goldman A, Edwards JC, Leiphart JW, Wharen RE, Fessler J, Fountain NB, Worrell GA, Gross RE, Eisenschenk S, Duckrow RB, Hirsch LJ, Bazil C, O'Donovan CA, Sun FT, Courtney TA, Seale CG, Morrell MJ. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. 2014 Mar;55(3):432-41. doi: 10.1111/epi.12534. Epub 2014 Feb 22.
• Morrell MJ; RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. 2011 Sep 27;77(13):1295-304. doi: 10.1212/WNL.0b013e3182302056. Epub 2011 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): January 1, 2026

Study Registration Dates

• First Submitted: March 26, 2015
• First Submitted That Met QC Criteria: March 26, 2015
• First Posted (Estimated): March 31, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: NP10012; PMA100026 (Other Identifier: United States FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO