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RNS System LGS Feasibility Study

Primary Purpose

Epilepsy, Lennox Gastaut Syndrome, Lennox-Gastaut Syndrome, Intractable

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

RNS System

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Medically refractory, Responsive neurostimulation, RNS System, Thalamocortical stimulation

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant is 15 years of age or older for first cohort; 12 years of age or older for second cohort. Note that age requirements for eligibility differ by cohort, as follows: the age limit for Cohort 1 is 15 years of age and above and the age limit for Cohort 2 may decrease to 12 years, pending a DSMB letter of recommendation, based on review of interim data analysis and concurrence with NINDS.
Participant has medically intractable epilepsy defined as failure to achieve acceptable seizure control without unacceptable medication related side effects despite trials of 2 or more antiseizure medications.
Participant had an average of ≥ 5 drop seizures per month in the 2 months preceding enrollment. A drop seizure is defined as an epileptic seizure (atonic, tonic, tonic-clonic, or myoclonic) involving the entire body, trunk, or head that leads or could lead to a fall, injury, or slumping in a chair.
Participant's seizures are non-localized.
Participant's scalp recorded EEG has features of LGS, such as multifocal spike, slow spike and wave discharges, and paroxysmal fast activity.
Participant must (a) have a stable antiseizure medication (ASM) regimen for the 2 months preceding enrollment and (b) be willing to remain on the stable regimen, as medically able, through the Blinded Evaluation Period; rescue medication for acute seizure clusters are permitted. A stable ASM regimen is defined as no introduction or discontinuation of an ASM, and no change in an ASM dose of more than 25%.
Participant is not on a therapeutic diet for epilepsy, or if participant is on a therapeutic diet for epilepsy must (a) have a stable diet for the 2 months preceding enrollment and (b) be willing to remain on the stable diet, as medically able, through the Blinded Evaluation Period.
Participant does not have a vagus nerve stimulator (VNS), or if participant does have a VNS must (a) have had the VNS off for the 2 months preceding enrollment and (b) be willing to remain with the VNS off through the Blinded Evaluation Period.
Participant is a 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 is willing to give informed consent (or assent, if a minor); if the participant assents or is not able to give informed consent, parent/legal guardian is willing to give informed consent.
Participant is able to maintain a seizure log alone or with the assistance of a competent individual.
Participant is able to attend study appointments in accordance with the study schedule.

Exclusion Criteria:

Participant is participating in a therapeutic investigational drug or device study (including other RNS System studies).
Participant is currently implanted with an electronic medical device that delivers electrical energy to the brain.
Participant is currently implanted with an RNS Neurostimulator or NeuroPace Leads.
Participant requires procedures that are contraindicated based on current RNS System labeling.
Participant is pregnant.
Participant has a diagnosed unstable psychiatric disorder or any attempt or expressed intent of suicide over the preceding 6 months.
In the opinion of the investigator, the participant has a clinically significant or unstable medical condition [including alcohol, opioid, recreational cannabis (not for therapeutic purposes) or other drug use disorder] or a progressive central nervous system disease.
Participant is taking any anticoagulants.
In the opinion of the investigator, participant is an unsuitable candidate for this procedure.
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 has had therapeutic surgery to treat epilepsy in the preceding 3 months. Participants who have had epilepsy surgery more than 3 months prior to enrollment are eligible.

Note: For contraindications, refer to current physician labeling (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

Sites / Locations

University of Alabama at BirminghamRecruiting
University of California, San FranciscoRecruiting
Emory UniversityRecruiting
Massachusetts General HospitalRecruiting
NYU Langone Medical CenterRecruiting
Mount Sinai HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Condition A

Condition B

Arm Description

high-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst)

low-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst)

Outcomes

Primary Outcome Measures

Safety: Annual device-related serious adverse event (SADE) rate

The lower limit of the 95% confidence interval of the annual SADE rate at months 12 and 24 post-implant is less than 33.6% and 22.0%, respectively (twice the SADE rate of 16.8% and 11.0%, respectively, at the same time points in the RNS System pivotal study)

Safety: Annual device-related serious adverse event (SADE) rate

Effectiveness: Blinded evaluation period (BEP) responder rate

The responder rate during one or both of the stimulation conditions (A or B) is ≥ 30%. The responder rate is the proportion of participants that are responders. A responder in this study is defined as a participant who has a ≥ 35% reduction in the frequency of drop seizures compared to that participant's pre-implant baseline.

Secondary Outcome Measures

Safety: Post-op SAE rate

The lower limit of the 95% confidence interval of the SAE rate following the implant procedure (through 4 weeks post-op) is less than 24% (twice the SAE rate of 12% at the same time point in the RNS System pivotal study).

Full Information

NCT ID

NCT05339126

First Posted

March 29, 2022

Last Updated

May 16, 2023

Sponsor

NeuroPace

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS), University of Florida

1. Study Identification

Unique Protocol Identification Number

NCT05339126

Brief Title

RNS System LGS Feasibility Study

Official Title

RNS System Feasibility Study of Thalamocortical Brain-Responsive Neurostimulation for the Treatment of Lennox-Gastaut Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 4, 2022 (Actual)

Primary Completion Date

November 30, 2026 (Anticipated)

Study Completion Date

May 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NeuroPace

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS), University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To generate preliminary safety and effectiveness data for brain-responsive neurostimulation of thalamocortical networks as an adjunctive therapy in reducing the frequency of generalized seizures in individuals 12 years of age or older with Lennox Gastaut Syndrome (LGS) who are refractory to antiseizure medications. The intent is to determine the feasibility and the optimal design of a subsequent pivotal study in order to expand the indication for use for the RNS System as a treatment for patients with medically intractable LGS.

Detailed Description

This study is a prospective two-stage single-blind feasibility cross-over study designed to provide early safety and preliminary evidence of effectiveness for combined bilateral brain-responsive neurostimulation of thalamocortical networks for the treatment of generalized seizures in patients with LGS. Twenty participants will be treated with the RNS System across six Comprehensive Epilepsy Centers in the U.S. Enrollment will be staged in two cohorts of 10. Once all 10 participants of the first cohort complete Treatment Block 1 and the interim analysis criteria are met, the next cohort of 10 participants will be enrolled. The research study comprises six study periods: Baseline Period Implant (surgery) Post-Op Period Blinded Evaluation Period (which is made up of 3 treatment blocks, one of which is a sham stimulation) Open Label Period Long Term Follow-Up Period Two neurostimulators will be placed: one in the parieto-temporal skull on the left, and the second in the homologous region on the right. Depth leads will target the bilateral CM. Cortical strip or depth leads will target the prefrontal cortex. Each neurostimulator will be connected to two ipsilateral leads: one in the prefrontal cortex and one in the CM. A total of two neurostimulators and four leads will be implanted. During the Blinded Evaluation Period, the participant will move through 3 different treatment blocks (Treatment Block1, Treatment Block 2, and Treatment Block 3) in a random order. Two of the blocks will have active stimulation treatment and one of the blocks will have no (sham) stimulation treatment. The participant and caregiver will be blinded to the treatment condition. Condition A - active treatment of high frequency short burst stimulation Condition B - active treatment of low frequency long burst stimulation Sham - no stimulation treatment After completing the Blinded Evaluation Period the participant will transition to the 1-year Open Label Period and have study appointments every 3 months. After completing the 1-year Open Label Period the participant will transition to the Long Term Follow-up Period. The Long-Term Follow-up Period may last up to 2 years with appointments every 3 months until the participant complete this research or this research study ends.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy, Lennox Gastaut Syndrome, Lennox-Gastaut Syndrome, Intractable, Seizures, Seizures, Generalized

Keywords

Medically refractory, Responsive neurostimulation, RNS System, Thalamocortical stimulation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Condition A

Arm Type

Active Comparator

Arm Description

high-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst)

Arm Title

Condition B

Arm Type

Active Comparator

Arm Description

low-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst)

Intervention Type

Device

Intervention Name(s)

RNS System

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety: Annual device-related serious adverse event (SADE) rate

Description

Time Frame

12 months post-implant

Title

Safety: Annual device-related serious adverse event (SADE) rate

Description

Time Frame

24 months post-implant

Title

Effectiveness: Blinded evaluation period (BEP) responder rate

Description

Time Frame

12 months post-implant

Secondary Outcome Measure Information:

Title

Safety: Post-op SAE rate

Description

Time Frame

4 weeks post-implant

Other Pre-specified Outcome Measures:

Title

Rate of SAEs of particular relevance

Description

The annual event rate of SAEs of particular relevance (device-related or not) will be calculated over time of study participation. SAEs of particular relevance include those related to: death, erosion, infection, suicidality, depression, hemorrhage, seizure-related injury, and tolerability of stimulation

Time Frame

Every 12 months post-implant

Title

Affective status

Description

Affective status (by summary scores from the Beck Depression Inventory, either the BDI-II or BYI-II, depending on age at time of the initial clinic appointment) will be described for the pre-implant baseline, as well as at the transition to Treatment Block 1, Treatment Block 2, Treatment Block 3, and Open Label; and for every 6 months thereafter that the participant is in the study.

Time Frame

Implant through 4 years post-implant

Title

Cognitive function

Description

Neuropsychological functioning as assessed by neuropsychological testing with validated, standardized inventories to assess domains that include attention (Flanker Inhibitory Control and Attention Test). The inventory is taken from the NIH Toolbox Cognition Battery and will be described by presenting summary scores for the pre-implant baseline, as well as for the end of the Blinded Evaluation Period and for the end of the Open Label Period.

Time Frame

Implant through 2 years post-implant

Title

Cognitive function

Description

Neuropsychological functioning as assessed by neuropsychological testing with validated, standardized inventories to assess three domains that include memory (Picture Sequence Memory Test). The inventory is taken from the NIH Toolbox Cognition Battery and will be described by presenting summary scores for the pre-implant baseline, as well as for the end of the Blinded Evaluation Period and for the end of the Open Label Period.

Time Frame

Implant through 2 years post-implant

Title

Cognitive function

Description

Neuropsychological functioning as assessed by neuropsychological testing with validated, standardized inventories to assess three domains that include vocabulary (Picture Vocabulary Test). The inventory is taken from the NIH Toolbox Cognition Battery and will be described by presenting summary scores for the pre-implant baseline, as well as for the end of the Blinded Evaluation Period and for the end of the Open Label Period.

Time Frame

Implant through 2 years post-implant

Title

Median percent change in seizure counts

Description

Median percentage change in counts of: Drop seizures, and Tonic-clonic seizures during both stimulation conditions (A and B), and every year thereafter while participating in the study, compared to that participant's pre-implant baseline

Time Frame

Implant through 4 years post-implant

Title

Days with seizures

Description

Days with: Any type of seizure Drop seizures Non-drop seizures during pre-implant baseline, during both stimulation conditions (A and B), and every year thereafter while participating in the study. A non-drop seizure is defined as an absence seizure, a myoclonic seizure, or an atonic or tonic seizure not leading to a fall.

Time Frame

Implant through 4 years post-implant

Title

Participant quality of life as measured by the QOLIE-AD-48

Description

Quality of life for the pre-implant baseline, as well as at the transitions to Treatment Block 1, Treatment Block 2, Treatment Block 3, and Open Label; and for every 6 months thereafter that the participant is in the study according to the QOLIE-AD-48 (validated for ages 12-17 years, depending on age at time of assessment).

Time Frame

Implant through 4 years post-implant

Title

Participant quality of life as measured by the QOLIE-31-P

Description

Quality of life for the pre-implant baseline, as well as at the transitions to Treatment Block 1, Treatment Block 2, Treatment Block 3, and Open Label; and for every 6 months thereafter that the participant is in the study, according to the QOLIE-31-P (validated for ages 18 and older, depending on age at time of assessment).

Time Frame

Implant through 4 years post-implant

Title

Caregiver burden

Description

Caregiver burden for the pre-implant baseline, as well as at the transitions to Treatment Block 1, Treatment Block 2, Treatment Block 3, and Open Label; and for every 6 months thereafter that the participant is in the study, according to the following scales: • Modified Caregiver Strain Index (MCSI)

Time Frame

Implant through 4 years post-implant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant is 15 years of age or older for first cohort; 12 years of age or older for second cohort. Note that age requirements for eligibility differ by cohort, as follows: the age limit for Cohort 1 is 15 years of age and above and the age limit for Cohort 2 may decrease to 12 years, pending a DSMB letter of recommendation, based on review of interim data analysis and concurrence with NINDS. Participant has medically intractable epilepsy defined as failure to achieve acceptable seizure control without unacceptable medication related side effects despite trials of 2 or more antiseizure medications. Participant had an average of ≥ 5 drop seizures per month in the 2 months preceding enrollment. A drop seizure is defined as an epileptic seizure (atonic, tonic, tonic-clonic, or myoclonic) involving the entire body, trunk, or head that leads or could lead to a fall, injury, or slumping in a chair. Participant's seizures are non-localized. Participant's scalp recorded EEG has features of LGS, such as multifocal spike, slow spike and wave discharges, and paroxysmal fast activity. Participant must (a) have a stable antiseizure medication (ASM) regimen for the 2 months preceding enrollment and (b) be willing to remain on the stable regimen, as medically able, through the Blinded Evaluation Period; rescue medication for acute seizure clusters are permitted. A stable ASM regimen is defined as no introduction or discontinuation of an ASM, and no change in an ASM dose of more than 25%. Participant is not on a therapeutic diet for epilepsy, or if participant is on a therapeutic diet for epilepsy must (a) have a stable diet for the 2 months preceding enrollment and (b) be willing to remain on the stable diet, as medically able, through the Blinded Evaluation Period. Participant does not have a vagus nerve stimulator (VNS), or if participant does have a VNS must (a) have had the VNS off for the 2 months preceding enrollment and (b) be willing to remain with the VNS off through the Blinded Evaluation Period. Participant is a 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 is willing to give informed consent (or assent, if a minor); if the participant assents or is not able to give informed consent, parent/legal guardian is willing to give informed consent. Participant is able to maintain a seizure log alone or with the assistance of a competent individual. Participant is able to attend study appointments in accordance with the study schedule. Exclusion Criteria: Participant is participating in a therapeutic investigational drug or device study (including other RNS System studies). Participant is currently implanted with an electronic medical device that delivers electrical energy to the brain. Participant is currently implanted with an RNS Neurostimulator or NeuroPace Leads. Participant requires procedures that are contraindicated based on current RNS System labeling. Participant is pregnant. Participant has a diagnosed unstable psychiatric disorder or any attempt or expressed intent of suicide over the preceding 6 months. In the opinion of the investigator, the participant has a clinically significant or unstable medical condition [including alcohol, opioid, recreational cannabis (not for therapeutic purposes) or other drug use disorder] or a progressive central nervous system disease. Participant is taking any anticoagulants. In the opinion of the investigator, participant is an unsuitable candidate for this procedure. 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 has had therapeutic surgery to treat epilepsy in the preceding 3 months. Participants who have had epilepsy surgery more than 3 months prior to enrollment are eligible. Note: For contraindications, refer to current physician labeling (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tricia Cunningham

Phone

831-854-3585

tcunningham@neuropace.com

First Name & Middle Initial & Last Name or Official Title & Degree

Julie Harvey Park

Phone

650-279-8599

jpark@neuropace.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martha Morrell, MD

Organizational Affiliation

NeuroPace, Inc.

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Samantha Fry

sdfry@uabmc.edu

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Vikram Rao, MD

Vikram.Rao@ucsf.edu

Facility Name

Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yvan Bamps

yvan.bamp@emory.edu

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Andrew Cole

First Name & Middle Initial & Last Name & Degree

Afareen Jaleel

AJALEEL@mgh.harvard.edu

Facility Name

NYU Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel Friedman, MD

First Name & Middle Initial & Last Name & Degree

Jack Carter

Jack.Carter@nyulangone.org

Facility Name

Mount Sinai Hospital

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Saadi Ghatan, MD

First Name & Middle Initial & Last Name & Degree

Armand Harb

Armand.Harb@mountsinai.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The following data types will be uploaded to the Data Archive for the BRAIN Initiative (DABI): Medical imaging: MRI, CT Neurophysiological recordings: intracranial EEG recordings Data collected from RNS Neurostimulator, reformatted for analysis. Clinical Trial Outcome and Endpoint data. Treatment condition status for subjects. Data will be uploaded every 6 months. Access is restricted and must be requested.

IPD Sharing Time Frame

The dataset and any supporting documentation (including but not limited to the study protocol, statistical analysis plan, and data dictionary) required for the analysis of the data will be made available within one year of the primary publication or within 18 months of the last study visit of the last subject, whichever occurs first.

IPD Sharing Access Criteria

Requestors will provide a CV, a description of their resources & facilities, along with a description of their planned analyses. Requests will be evaluated by a Research Review Committee at NeuroPace in accordance with NeuroPace data sharing policies. Approved requests will require execution of a data access agreement based on NeuroPace's existing template.

IPD Sharing URL

https://dabi.loni.usc.edu/dsi/UH3NS109557

Learn more about this trial

RNS System LGS Feasibility Study

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