Clinical trial NCT05147571: RNS System NAUTILUS Study
Official title: RNS® System Responsive Thalamic Stimulation for Primary Generalized Seizures (NAUTILUS) Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Epilepsy
Idiopathic Generalized Epilepsy
Generalized Tonic Clonic Seizure
Keywords: Medically refractory
Responsive neurostimulation
RNS System
Thalamic stimulation
Lead sponsor: NeuroPace
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: NeuroPace is sponsoring the NAUTILUS Study with the RNS System for thalamic stimulation as an adjunctive therapy for the treatment of generalized seizures in individuals 12 years of age or older who have drug-resistant idiopathic generalized epilepsy. The RNS System is currently approved by the FDA for use in patients 18 years and older with hard-to-treat partial-onset seizures. The same device will be used in the NAUTILUS Study.

The study is a prospective, multicenter, single-blind, randomized, sham stimulation controlled pivotal study and participants will be followed for two years after placement of the RNS System. The study will enroll a maximum of 100 participants within the United States to ensure that at least 80 participants are implanted with the RNS System.

The study design includes a two-month retrospective and one-month prospective baseline. All participants will have detection enabled at the time of implant. At one month post-implant, participants will be randomized 1:1 to Active or Sham stimulation. For those randomized to the Active group, stimulation will be enabled. Participants will be blinded to their own randomization status until the 2nd GTC occurs for that individual, they completed the 9-month Effectiveness Evaluation Period (12-months post-implant), or the 60th GTC-event occurs in the group, whichever occurs first. After that, patients will be unblinded and patients in the Sham group (responsive stimulation OFF) will have responsive stimulation enabled (responsive stimulation ON).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 12-week post-operative serious device-related adverse event (SADE) rate
timeFrame: 84 days post-implant (12 weeks)
measure: Time to second generalized tonic-clonic (GTC) seizure
timeFrame: 9-month Effectiveness Evaluation Period
Secondary outcomes:
measure: Percent change in monthly rate of days with any type of generalized seizure (generalized tonic-clonic, myoclonic, absence)
timeFrame: 9-month Effectiveness Evaluation Period
Other outcomes:
measure: Annual event rate of Serious Adverse Device Effects (SADEs)
timeFrame: Implant through 2 years post-implant
measure: Annual event rate of Serious Adverse Events (SAEs) of particular relevance
timeFrame: Implant through 2 years post-implant
measure: Affective status as assessed by the Beck Depression Inventory
timeFrame: Pre-implant baseline through 2 years post-implant
measure: Neuropsychological functioning as assessed by a sub-set of tests in the NIH Toolbox Cognition Battery
timeFrame: Pre-implant baseline through 2 years post-implant
measure: Sleep assessment as assessed by sleep habit questionnaires
timeFrame: Pre-implant baseline through 2 years post-implant
measure: Health affecting behaviors assessment
timeFrame: Pre-implant baseline through 2 years post-implant
measure: Percent change in seizure frequency
timeFrame: Blinded Effectiveness Evaluation Period (3 months post-implant up to Time-to-Generalized-Tonic-Clonic-Event)
measure: Quality of life as assessed by the Quality of Life in Epilepsy Inventory
timeFrame: Pre-implant baseline through 2 years post-implant
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lebanon
country: United States
facility: Mary Hitchcock Memorial Hospital (Dartmouth)
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: New York University Langone
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Healthcare
state: Utah
Study officials:
affiliation: NeuroPace, Inc.
name: Martha Morrell, MD
role: PRINCIPAL_INVESTIGATOR
References: