RNS® System LTT Study

Study Overview
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Brief Summary
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The RNS® System LTT study is designed to assess the ongoing safety and to evaluate the long-term efficacy 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 that are refractory to two or more antiepileptic medications. Candidates will continue to receive their epilepsy medications while participating in the trial.

Detailed Description
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NeuroPace, Inc. is sponsoring an investigational device study of the RNS® System, the first closed loop responsive brain stimulator designed to treat refractory epilepsy. The RNS® System LTT study is an open-label multi-center prospective 7-year clinical investigation which follows completion of the RNS® System Pivotal or Feasibility study. Data regarding safety and efficacy are collected at 6-month intervals, and data regarding quality of life are collected at yearly intervals. The study is designed to assess the ongoing safety and to evaluate the long-term efficacy of the RNS® System as an adjunctive therapy in reducing the frequency of medically uncontrolled and disabling partial onset seizures that start from one or two areas of the brain. The RNS® System LTT study will provide additional data on the safety and efficacy of the RNS® System for 7 years following a subject's completion of the RNS® System Feasibility or Pivotal studies. Data from the RNS® System LTT study will be combined with data collected during the RNS® System Feasibility and Pivotal studies, resulting in 9 total years of post-implant follow-up data. These data will be used to calculate long-term SAE rate, percent change in seizure frequency (from pre-implant baseline), as well as the frequency of sudden unexplained death in epilepsy (SUDEP). The RNS® Neurostimulator (a pacemaker-like device) and NeuroPace® Leads (tiny wires with electrodes) are implanted in the head. The Neurostimulator is a battery powered, microprocessor controlled device that detects and stores records of electrographic patterns (such as epileptiform, or seizure-like, activity) from the Leads within the brain. When the device detects an electrographic pattern, it responds by sending electrical stimulation through the Leads to a small part of the patient's brain to interrupt the electrographic pattern. This type of treatment is called responsive stimulation, but it is not yet known if it will work for the treatment of epilepsy. Direct brain stimulation therapy has already received approval in the United States, Europe, Canada, and Australia for the treatment of Essential Tremor and Parkinson's disease. Direct brain stimulation is not approved for the treatment of epilepsy.

Official Title
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RNS® System Long-term Treatment (LTT) Clinical Investigation

Conditions
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Epilepsy

Intervention / Treatment
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* Device: RNS® System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has completed either the RNS® System Pivotal or Feasibility study Subject has an implanted RNS® System Subject has elected to continue to receive responsive neurostimulation therapy after completion of the RNS® System Pivotal or Feasibility study Subject is able to attend scheduled appointments for the RNS® System LTT study Exclusion Criteria: Subject has active psychiatric or medical illness that makes it inadvisable for the subject to continue to receive responsive neurostimulation therapy with the RNS® System Subject has been diagnosed with psychogenic or non-epileptic seizures, or primarily generalized seizures during the RNS® System Pivotal or Feasibility study Subject has been noncompliant with scheduled appointments during the RNS® System Pivotal or Feasibility study Subject has been noncompliant with maintaining seizure diaries during the RNS® System Pivotal or Feasibility study Informed consent cannot be obtained from subject or caregiver

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evaluation Group (stimulation ON)<br>Group of subjects that have an RNS® System implanted, completed the RNS® System Pivotal or Feasibility study, and elected to continue to receive RNS® System responsive stimulation for the long term. | Device: RNS® System<br>* The previously implanted RNS® System is programmed to provide responsive stimulation. Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal, the Neurostimulator provides brief pulses of electrical stimulation through the Leads to interrupt those patterns. Patients with epilepsy treated with responsive direct-brain stimulation with the RNS System typically receive less than 6 minutes of stimulation a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAE) | The number of subjects having an SAE during the RNS® System LTT study. | 2 years post-implant through 9 years post-implant (7 years) | 
| Percentage Change From Baseline in Seizure Frequency | The average percentage change in the mean frequency of total disabling seizures relative to pre-implant baseline. The percent change will be calculated for each subject over 6-month intervals beginning 6 months after RNS® System implant and continuing through completion of the RNS® System LTT study. | 6 months post-implant through 9 years post-implant (8.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate | The proportion of subjects with greater than or equal to 50% reduction in total disabling seizures compared to pre-implant baseline. | 6 months post-implant through 9 years post-implant (8.5 years) | 
| QOLIE (Quality of Life in Epilepsy) | QOLIE 89 (for English-speaking subjects) or QOLIE 31 P (for Spanish speaking subjects) scores collected at each year of follow-up after implantation of the RNS® System compared to the QOLIE 89 / QOLIE 31 P at pre-implant baseline. A QOLIE overall score was obtained using a weighted average of multi-item scale scores. The QOLIE overall score was converted to a T-score, a normally distributed scale with a mean score of 50 and standard deviation (SD) of 10. Higher scores reflect a better quality of life. | 1 year post-implant through 9 years post-implant (8 years) | 
| Adverse Event Rate | The rate of occurrence of any adverse event (AE) observed during the Long-term Treatment Investigation. | 6 months post-implant through 9 years post-implant (8.5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Responsive neurostimulation, RNS System, NeuroPace, Brain stimulation, Seizures