RNS System NAUTILUS Study

NCT05147571 | Active Not Recruiting Phase 3 DMC FDA Device

• 1 other identifier: NP10016
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 23

Brief Summary

To demonstrate that the RNS System for thalamic stimulation is safe and effective as an adjunctive therapy for the reduction of primary generalized seizures in individuals 12 years of age or older who have drug-resistant idiopathic generalized epilepsy.

Conditions

Epilepsy; Idiopathic Generalized Epilepsy; Generalized Tonic Clonic Seizure

Keywords

Medically refractory; Responsive neurostimulation; RNS System; Thalamic stimulation

Outcome Measures

Primary Outcomes (2)

• 12-week post-operative serious device-related adverse event (SADE) rate

  The primary safety endpoint is the percent of participants with serious device-related adverse events (SADE) at 84 days (12 weeks) post-implant.

  84 days post-implant (12 weeks)

• Time to second generalized tonic-clonic (GTC) seizure

  The primary effectiveness endpoint is the time to a participant's 2nd GTC seizure (also defined as a GTC-event) during the 9-month Effectiveness Evaluation Period. Across participants, once the 60th GTC-event occurs, the study will have collected the necessary data to assess the primary effectiveness endpoint; all participants will then be unblinded.

  9-month Effectiveness Evaluation Period

Secondary Outcomes (1)

• Percent change in monthly rate of days with any type of generalized seizure (generalized tonic-clonic, myoclonic, absence)

  9-month Effectiveness Evaluation Period

Other Outcomes (8)

• Annual event rate of Serious Adverse Device Effects (SADEs)

  Implant through 2 years post-implant

• Annual event rate of Serious Adverse Events (SAEs) of particular relevance

  Implant through 2 years post-implant

• Affective status as assessed by the Beck Depression Inventory

  Pre-implant baseline through 2 years post-implant

Study Arms (2)

Active Group (responsive stimulation ON)

ACTIVE COMPARATOR

Participants are implanted with the RNS System and are receiving treatment with responsive stimulation.

Device: Responsive stimulation

Sham Group (responsive stimulation OFF)

SHAM COMPARATOR

Participants are implanted with the RNS System and are not receiving treatment with responsive stimulation.

Device: Sham stimulation

Interventions

Responsive stimulation DEVICE

The RNS System provides closed loop responsive brain stimulation. The Neurostimulator monitors the electrical activity of the brain to detect abnormal activity that could lead to a seizure. If abnormal activity is detected, the neurostimulator delivers electrical stimulation to the brain through the leads to help prevent the seizure before it occurs.

Active Group (responsive stimulation ON)

Sham stimulation DEVICE

For those in the Sham Stimulation group, the RNS System will be set to detect abnormal activity but will not have responsive stimulation enabled. Both Sham and Active groups will undergo therapy testing at each appointment in order to maintain the blind.

Sham Group (responsive stimulation OFF)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is age 12 and older.
• Participant is male or is a female of childbearing potential who is surgically sterile, 2 years postmenopausal, or practices a reliable method of contraception (hormonal, barrier method or abstention).
• Participant failed treatment with a minimum of two antiseizure medications (used in appropriate doses) with adequate monitoring of compliance and the effects of treatment, as determined by the investigator.
• Participant is able to maintain an electronic diary alone or with the assistance of a competent individual.
• Participant is able to attend clinic appointments in accordance with the study schedule.
• Participant or parent(s) or legal representative have signed an IRB approved written informed consent/assent. The informed consent form or specific assent form, where required, will be signed and dated by minors.
• Participant is not currently implanted with an RNS Neurostimulator or NeuroPace Leads.
• In the investigator's opinion, participant is able to tolerate a neurosurgical procedure.
• Participant with a confirmed diagnosis of idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, with or without myoclonic or absence seizures, consistent with the International League against Epilepsy Revised Classification of Seizures (2017).
• Participant has had 2 or more generalized tonic-clonic seizures during the two month retrospective baseline.
• Participant has had a routine electroencephalogram (EEG) within 2 years prior to enrollment with electroencephalographic features consistent with idiopathic generalized epilepsy; other concomitant anomalies must be explained by adequate past medical history.
• Participant has been on a stable antiseizure medication (ASM) regimen during the two month retrospective baseline and is willing to remain on a stable ASM regimen during the prospective Baseline and throughout the Effectiveness Evaluation Period, if medically possible; rescue benzodiazepine medications for acute seizure clusters are permitted.
• Participant has undergone computed tomography (CT) or magnetic resonance imaging (MRI) within 10 years prior to enrollment that ruled out a progressive cause of epilepsy or an abnormality likely to be associated with focal-onset seizures.
• Participant does not have a vagus nerve stimulator (VNS, LivaNova) or Participant's VNS is OFF during the two month retrospective baseline and participant is willing to keep the VNS off during the study.

You may not qualify if:

• Participant is pregnant.
• Participant is participating in a therapeutic investigational drug or other device study.
• Participant is implanted with an electronic medical device that delivers electrical energy to the brain.
• Participant requires procedures that are contraindicated based on current RNS System labeling.
• Participant has been diagnosed with active psychosis, major depression or suicidal ideation in the preceding year. Participants with post-ictal psychiatric symptoms need not be excluded.
• In the opinion of the investigator, the participant has a clinically significant or unstable medical condition (including alcohol and/or drug abuse) or a progressive central nervous system disease.
• Participant has a history of partial-onset seizures or EEG findings within the past 2 years indicative of partial-onset or symptomatic generalized abnormalities.
• Participant has been diagnosed with psychogenic or non-epileptic seizures in the preceding year.
• Participant has experienced unprovoked status epilepticus in the preceding year.
• Participant is taking any anticoagulants.

Sponsors & Collaborators

• NeuroPace: lead

Study Sites (23)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Spectrum Health Butterworth Hospital

Grand Rapids, Michigan, 48503, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55902, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Mary Hitchcock Memorial Hospital (Dartmouth)

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

New York University Langone

New York, New York, 10016, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Epilepsy; Epilepsy, Idiopathic Generalized; Epilepsy, Tonic-Clonic

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized

Study Officials

• Martha Morrell, MD

  NeuroPace, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 7, 2021
• Study Start: August 9, 2022
• Primary Completion: April 4, 2025
• Study Completion: March 1, 2026
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)