EpilepsyPhase 2NCT05339126
RNS System LGS Feasibility Study
A Phase 2 study testing RNS System in people with Epilepsy and Lennox Gastaut Syndrome, run by NeuroPace at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Epilepsy, Lennox Gastaut Syndrome, Lennox-Gastaut Syndrome, Intractable
- What is being tested?
- RNS System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 6 sitesUnited States
- Study dates
- 4 Oct 2022to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%.
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Emory University
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
NYU Langone Medical Center
New York, New York, 10016
Mount Sinai Hospital
New York, New York, 10029
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: RNS System Feasibility Study of Thalamocortical Brain-Responsive Neurostimulation for the Treatment of Lennox-Gastaut Syndrome
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.
Read the 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.
- Conditions
- Epilepsy, Lennox Gastaut Syndrome, Lennox-Gastaut Syndrome, Intractable, Seizures, Seizures, Generalized
- Being tested
- RNS System
- Keywords
- Medically refractory, Responsive neurostimulation, RNS System, Thalamocortical stimulation
- Medical subject headings
- Epilepsy, Lennox Gastaut Syndrome, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RNS SystemDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Condition A | Active comparator | high-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst) Receives: Device: RNS System |
| Condition B | Active comparator | low-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst) Receives: Device: RNS System |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 12 months post-implant
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)
Measured: 24 months post-implant
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.
Measured: 12 months post-implant
Secondary outcomes (1)
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).
Measured: 4 weeks post-implant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2022
- Study start4 Oct 2022
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NeuroPace
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Florida
- Responsible party
- Sponsor
- Investigators
- Martha Morrell, MD, Principal investigator, NeuroPace, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05339126
- Sponsor's protocol ID
- NP10015
- Other IDs
- UH3NS109557
- Status last verified
- Sep 2026
- First submitted
- 29 Mar 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Publications
Dary Z, Warren AEL, Hook MP, Chabros J, Johnson L, Morrell MJ, Butson CR, Rolston JD. Circadian modulation of aperiodic background and oscillatory activity as a biomarker of seizure burden in Lennox-Gastaut syndrome. Epilepsia. 2026 Aug 28. doi: 10.1002/epi.70457. Online ahead of print.
PubMed 42663529
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RNS System Feasibility Study of Thalamocortical Brain-Responsive Neurostimulation for the Treatment of Lennox-Gastaut Syndrome
- ClinicalTrials.gov ID
- NCT05339126
- Acronym / sponsor ID
- NP10015
- Conditions
- Epilepsy, Lennox Gastaut Syndrome, Lennox-Gastaut Syndrome, Intractable, Seizures, Seizures, Generalized
- Keywords
- Medically refractory, Responsive neurostimulation, RNS System, Thalamocortical stimulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- NeuroPaceIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Florida
- Study start
- 4 Oct 2022 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 21 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Condition A | Active comparator | Device: RNS Systemhigh-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst) |
| Condition B | Active comparator | Device: RNS Systemlow-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst) |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RNS SystemThe 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. | Device | Condition A, Condition B |
Primary outcome
Safety: Annual device-related serious adverse event (SADE) rate
Time frame: 12 months post-implant
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
Time frame: 24 months post-implant
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)
Effectiveness: Blinded evaluation period (BEP) responder rate
Time frame: 12 months post-implant
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.
1 secondary outcome
Safety: Post-op SAE rate
Time frame: 4 weeks post-implant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Derived from this study: PubMed 42663529Dary Z, Warren AEL, Hook MP, Chabros J, Johnson L, Morrell MJ, Butson CR, Rolston JD. Circadian modulation of aperiodic background and oscillatory activity as a biomarker of seizure burden in Lennox-Gastaut syndrome. Epilepsia. 2026 Aug 28. doi: 10.1002/epi.70457. Online ahead of print.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martha Morrell, MD principal investigator
NeuroPace, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RNS System in people with Epilepsy and Lennox Gastaut Syndrome, run by NeuroPace at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Annual device-related serious adverse event (SADE) rate (time frame: 12 months post-implant). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05339126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.